Methods

Overview

Fluxion is a mechanistic simulation: every reaction carries kinetic and thermodynamic constants, and the behaviour on screen is the consequence of those numbers rather than a scripted animation. This page records where those numbers come from — which are measured constants taken from the literature, and which are modelling choices made to keep a reduced-order, coupled model of skeletal muscle, liver, erythrocyte, and their shared bloodstream physiological. It is written so that a student or reviewer can check the model against its sources.

How to read this page

Each value is given beside the reaction it belongs to, using the model's own names (for example ComplexI, ATPSynthase). Three kinds of number appear:

• Vf — a forward velocity, in mM/s. It represents how much active catalyst is present, so it is the number an expression change, inhibitor, or knockdown moves. It is not a measured turnover number; it is a model-scaled capacity.
• Keq — an equilibrium constant, derived from thermodynamics (standard free energies or midpoint potentials) rather than fitted. Reverse velocities follow from Vf and Keq through the Haldane relationship, so the equilibrium position is fixed by chemistry, not chosen.
• Km — a half-saturation concentration, in mM, from measured enzyme affinities where these are known.

Citations. Each value is followed by a bracketed reference number — for example [1] — that links to the numbered References list at the foot of the page. A value with no bracketed number is a modelling choice rather than a measured quantity, and is labelled as such in the text; where the literature gives a different value, the entry says so and gives the reason.

Concentrations are in millimolar (mM); the mitochondrial membrane potential is a voltage in millivolts (mV). Compartments are marked by suffix: _c cytosol, _i intermembrane space, _m matrix, _b blood.

A note on matrix velocities. The model treats the cell as compartments with real relative volumes — cytosol 0.70, matrix 0.07, intermembrane space 0.02 of the cell. Because a matrix reaction is stated per liter of matrix, its velocity is multiplied by MATRIX_CAPACITY_SCALE = 0.70 / 0.07 = 10 to keep the same capacity per cell. Where a matrix Vf is quoted below as, say, 0.018 × 10, the first number is the per-liter value in the source and the second is that scaling.

Electron transport chain and oxidative phosphorylation

The respiratory chain is modelled as what it physically is: redox reactions that move charge across the inner membrane, and an ATP synthase that lets that charge back in to make ATP. The membrane potential is a real voltage that the complexes build and ATP synthase spends, not a fitted parameter.

Redox midpoint potentials and equilibrium constants

Each complex's equilibrium constant is derived from the standard midpoint potentials of its redox couples at pH 7 and 37 °C [5][3], using

ΔG = −n F ΔE and Keq = exp(−ΔG / RT), RT = 2577 J/mol at 310 K

with n = 2 electrons. The midpoint potentials used (volts) are the standard reference values [5]:

• NAD⁺/NADH −0.320
• FAD/FADH₂ +0.031 (the succinate-dehydrogenase-bound flavin)
• CoQ/CoQH₂ +0.045
• cytochrome c +0.254
• O₂/H₂O +0.816

which give:

• ComplexI — ΔE = 0.365 V, ΔG = −70.4 kJ/mol, Keq = 7.4 × 10¹¹ [5]
• ComplexII — ΔE = 0.014 V, ΔG = −2.7 kJ/mol, Keq = 2.85 [5]. Barely favourable, which is correct: the succinate flavin sits almost level with the quinone pool, and that narrow margin is why succinate yields less ATP than NADH.
• ComplexIII — ΔE = 0.209 V, ΔG = −40.3 kJ/mol, Keq = 6.3 × 10⁶ [5]
• ComplexIV — ΔE = 0.562 V, ΔG = −108.4 kJ/mol, Keq = 1.9 × 10¹⁸ [5]. Far from equilibrium at any physiological potential, which is why cytochrome c oxidase is effectively one-way and is the committed step.

Proton and charge stoichiometry

Per two electrons, which totals the accepted ten protons per NADH oxidised [5]:

• ComplexI — 4 H⁺ to the intermembrane space, 5 from the matrix (4 pumped, 1 for ubiquinone reduction); 4 charges [5].
• ComplexIII — 4 H⁺ to the intermembrane space, 2 from the matrix; 2 charges — two protons leave ubiquinol on the outer face and cross no membrane [5].
• ComplexIV — 2 H⁺ to the intermembrane space, 4 from the matrix (2 pumped, 2 forming water); 4 charges [5].

Every other reaction's integer H⁺ is the proton its species' reference forms need to balance charge and atoms — the fully deprotonated form of each phosphate and carboxylate group inside the 5.5–8 titration window: ATP⁴⁻, ADP³⁻, Pi²⁻, NAD⁻/NADH²⁻, CoA⁴⁻, citrate³⁻ and so on [86][87]. The cell's state variable is the total titratable proton, so the pH-dependent fractional proton of a phosphate interconversion (≈ 0.3 H⁺ for Pi → glucose-1-phosphate at pH 7) is handed to the free pool by the pH inversion itself and needs no term of its own [86]; the track_phosphate_protons terms that once added it a second time were removed. Tests/test_proton_stoichiometry.py audits every reaction against a charge table and fails on any imbalance outside a short, documented list of artificial boundary terms. That audit (OPEN-WORK 5.4, 2026-10) found and corrected:

• PyruvateDehydrogenase, IsocitrateDehydrogenase (the NAD-linked matrix and the NADP-linked cytosolic isoform) and AlphaKGDehydrogenase carried a proton each that their chemistry does not give — pyruvate⁻ + NAD⁻ + CoA⁴⁻ → acetyl-CoA⁴⁻ + CO₂ + NADH²⁻ balances with none [86][87].
• CitrateSynthase (the acetyl-CoA thioester hydrolysis), GlycogenSynthase, GlycerolKinase, F26BP_Synthesis (PFK-2) and HMGCoASynthase each release one proton the model omitted; PyruvateCarboxylase (and the liver's gluconeogenic copy) release two [86].

The placeholder and boundary terms follow the same rule where one is unambiguous (OPEN-WORK 5.1): the AMP recoveries (AMP²⁻ + Pi²⁻ + H⁺ → ADP³⁻), the NADPH sinks (NADPH⁴⁻ + H⁺ → NADP³⁻, as glutathione reductase), the peripheral ketone disposals (a ketone anion's oxidation takes up a proton, taken from the blood pool) and the 2,3-BPG mutase (BPG13⁴⁻ → BPG23⁵⁻ + H⁺) were brought to it. What stays unbalanced is documented in the test: the alanine transaminase, which lumps away the amino nitrogen and its reducing equivalents together (so the proton is not a stand-alone fix); Cataplerosis and the ribose-5-phosphate drain, whose protons are set by the unmodeled lipogenesis and nucleotide synthesis; PhosphateSupply, which moves the phosphate dianion across the model's edge (the pH inversion then hands its bound protons to, or takes them from, the free pool, as a real phosphate flux does); the Ca²⁺ co-release signal; and the acid-base regulator itself.

Together these over-released two protons per pyruvate oxidized (and let the liver's PFK-2/FBPase-2 cycle run alkaline). That is invisible at rest, where the compensating terms were calibrated against it, but it scales with the TCA flux: at a moderate 0.2 mM/s muscle demand (about 17× rest) it was a net acid load of about 10% of the ATP turnover, and the muscle cytosol fell from 6.95 to 6.70 in 20 minutes with blood lactate under 2 mM.

Rate law: exchange currents, not a maximum velocity

Complexes I, III, and IV use Butler–Volmer / Marcus electron-transfer kinetics rather than the reversible Michaelis–Menten law, so that Vf is an exchange current — a small internal resistance — rather than a saturating maximum. This is a modelling choice of rate-law form (no literature turnover number is implied): the small exchange current (Vf = 0.018 × 10) keeps the resting chain below its thermodynamic ceiling, which is what lets the membrane potential fall smoothly from rest to hard work. ComplexII (Vf = 0.85 × 10) is an ordinary reversible step, as it is not electrogenic. Km values for the electron carriers are 0.05 mM, within measured ranges [2].

ATP synthase

Reaction ATPSynthase: ADP + Pi + (8/3) H⁺ → ATP + H₂O + (8/3) H⁺. The mammalian enzyme has a ring of eight c-subunits and makes three ATP per revolution, so 8/3 protons per ATP [5]. The equilibrium constant comes from the free energy of ATP synthesis, ΔG = +30.5 kJ/mol, giving Keq = 7.3 × 10⁻⁶ [3] — driven entirely by the proton-motive force. Calcium activation (half-effect near 1 µM matrix Ca²⁺) is the demand half of parallel activation [6].

P/O ratio

The chain separates ten charges per NADH; ATP synthase spends 8/3 per ATP and the translocase one more, so 10 / (8/3 + 1) ≈ 2.7 ATP per NADH, against the accepted P/O ratio of about 2.5 once proton leak is included [12].

Proton leak

Reaction ProtonLeak: protons returning to the matrix outside ATP synthase. This accounts for roughly 20–25 % of resting mitochondrial oxygen consumption in skeletal muscle [13], and stops the potential running away when demand is low. It is modelled as a Hill function of the membrane potential (half-point 175 mV, coefficient 4, up to 25-fold), which reproduces the observed non-ohmic shape [13]; the exact Hill constants are a modelling choice fitted to that shape.

Membrane potential

Resting Dpsi_m settles near 180 mV (a respiring mitochondrion runs at roughly 150–190 mV) and falls toward the working range under load [5]. The pH gradient across the inner membrane adds a further ~25 mV, so the total proton-motive force is roughly Δψ + 25 mV [5].

Modelling choices called out honestly

• Ubiquinone midpoint potential (+0.045 V). This couple is the least certain of the five — reported values run from about +0.04 to +0.11 V [5] — and it is also the one the model is most sensitive to, because it sets how the driving force divides between Complex I and Complex III. +0.045 V is chosen because it is the value at which both near-equilibrium complexes still run forward; this is a modelling choice within the reported range.
• Phosphate carrier stoichiometry. The carrier is written with two protons per phosphate, where the literature usually gives one [5]. This is a compromise, made because the model lacks the potassium cycling that normally partitions the proton-motive force; with one proton the modelled matrix runs to pH 11. The total proton-motive force is correct either way — only its split between voltage and pH depends on it.

Glycolysis

Equilibrium constants (reversible steps)

Set to the apparent equilibrium constants at pH 7, which match the standard tabulated values [1][3] — except PGM, enolase and (below, anaerobic glycolysis) lactate dehydrogenase, where measured values replace the textbook free energies:

• PGI (glucose-6-P ⇌ fructose-6-P) — Keq = 0.35 [1]
• Aldolase (fructose-1,6-bisP ⇌ DHAP + GAP) — Keq = 0.08 [1]
• TPI (DHAP ⇌ GAP) — Keq = 0.045, favouring DHAP ~22:1 [1]
• GAPDH — Keq = 8 × 10⁻⁵ mM⁻¹, the 0.08 M⁻¹ of ΔG°′ ≈ +6.3 kJ/mol at pH 7 [3] in the model's units (phosphate is a reactant, so the constant carries a concentration unit). It was once entered as 0.08 in mM⁻¹ — 1000× too favourable — which drained every tissue's triose phosphates (muscle GAP ~0.3 µM, DHAP ~7 µM against ~15 / ~150 measured) and forced the red cell's cytosol to NAD⁺/NADH ~1. GAPDH and PGK run near equilibrium together; their in-vivo mass-action ratio in red cells and muscle gives an apparent constant ~5 × 10⁻⁵–3 × 10⁻⁴ mM⁻¹, consistent with the corrected value.
• PGK (1,3-bisphosphoglycerate + ADP ⇌ 3-PG + ATP) — Keq = 3300 [1]
• PGM (3-PG ⇌ 2-PG) — Keq = 0.10, the measured [2-PG]/[3-PG]: 0.087 ± 0.006 at pH 7.0 [93] and 0.086–0.116 at 20 and 30 °C over pH 5.4–7.9 and ionic strength 0.06–0.3 with Mg²⁺, with "little variation" within physiological ranges [94]. The textbook ΔG°′ ≈ +4.4 kJ/mol [3] (0.17) was replaced by the measurements (OPEN-WORK 4.3, 2026-10-08).
• Enolase (2-PG ⇌ PEP) — Keq = 4.7, from the measured ΔG°′ of −2.8 ± 0.2 kJ/mol at 25 °C and ΔH°′ of +27 ± 10 kJ/mol at pH 7 [92], extrapolated to 37 °C by the van't Hoff equation (3.9–5.5 over the enthalpy range; the 310 K measurement itself was not read). It was 0.50, from the textbook ΔG°′ ≈ +1.8 kJ/mol [3], and 4.4 before that (Fumarase's constant, copied across, right by accident). With PGM at 0.10 the pair puts PEP/3-PG at ~0.47 at equilibrium against 0.085 before, and ~0.3 in vivo in red cells (OPEN-WORK 4.3, 2026-10-08).

Regulated irreversible steps

• Hexokinase — Km(glucose) = 0.05 mM, the measured low-Km hallmark of hexokinase (versus liver glucokinase) [2]. Product inhibition by glucose-6-phosphate (Ki = 0.05 mM) is its classic feedback [3]. Idled (Vf 0) for the liver, which runs its own dedicated Glucokinase reaction instead (below) rather than an override of this one -- the missing G6P inhibition is a genuine mechanistic difference the override system (additive-only regulators) cannot express.
• Glucokinase (liver-only, §3.1) — the high-Km (10 mM), high-capacity hepatic isozyme [2] that keeps phosphorylating glucose as blood glucose rises after a meal, unlike muscle hexokinase, which self-limits. Genuinely carries NO glucose-6-phosphate product inhibition, matching the literature mechanism [3] -- the fix this reaction exists for; the former liver-tagged Hexokinase override kept the shared enzyme's G6P inhibitor because the override mechanism can only add regulators, never remove one. It carries a lumped hormonal gate standing in for the glucokinase regulatory protein (GKRP), which holds the enzyme inactive in the nucleus during fasting: an insulin activator (up to 5×) and a glucagon inhibitor, with the base Vf (0.0273) the sequestered floor. Ungated, it re-phosphorylated 67% of the glucose glucose-6-phosphatase released in a fast; gated and re-anchored to the post-absorptive rest (below), the resting liver's glucose ⇌ glucose-6-phosphate cycle is ~21% of glucose-6-phosphatase flux, close to the 14% measured in post-absorptive humans [34]. Its glucagon constant sits below the other hepatic gates' because GKRP's glucagon-held sequestration is what keeps that cycle low. The gate's gains are modelling choices.
• PFK1 — inhibited by ATP and by protons, activated by AMP: the direction of all three controls matches the textbook regulation of the committed, pH-sensitive step [4][3]. The AMP activation strength (up to 10-fold) has no specific literature value — the code marks it a placeholder chosen to exceed the engine's former 2-fold ceiling, and it should be traced to a source.
• PyruvateKinase — feed-forward activation by fructose-1,6-bisphosphate and inhibition by ATP; both match the established regulation of the M-type isozyme [3].
• The red cell's glycolysis. Its enzyme capacities are the measured normal human red-cell activities [56] (IU/g Hb at 37 °C, converted at 340 g Hb and 0.717 L water per L of cells): it used to run muscle's capacities for all but hexokinase and PFK-1 — pyruvate kinase ~40× and aldolase ~80× its own — which drained PEP and let the trioses pile up. The intact red cell throttles glycolysis at hexokinase (a few percent of capacity) and PFK-1 (~1%), and Mulquiney & Kuchel's control analysis found 2,3-BPG's feedback on both as important as any control of the cell's 2,3-BPG [57]. So its hexokinase (HK1) carries tight glucose-6-phosphate product inhibition (Ki 15 µM) plus 2,3-BPG (Ki 4 mM) and glutathione (Ki 3 mM) inhibition, its PFK-1 2,3-BPG inhibition (Ki 0.5 mM, set so PFK runs at ~1% of capacity), and its pyruvate kinase the erythroid PK-R's weaker PEP and ADP binding (Km 0.25 / 0.3 mM); the inhibition constants are first-pass within their reported orders. Its ATP demand (an artificial term) is ~2.2 mmol per L of cells per hour, the net yield of its measured glucose use. Result: glucose ~16.7 µmol/kg/min (~1.2 µmol/mL cells/h; 1.2–1.5 measured), lactate ~1.9× glucose, a true steady state, cytosolic NAD⁺/NADH ~840 and lactate/pyruvate ~9, PEP ~15 µM, pyruvate ~50 µM, ATP ~1.7 mM; the trioses and 3-PG rest ~3–10× their measured levels (OPEN-WORK 6.2). It previously took up ~3.7× its glucose and never reached a steady state (F1,6BP/DHAP ~2–3 mM and rising, cytosol NAD⁺/NADH ~0.24).

Forward velocities throughout glycolysis are model-scaled capacities, not measured turnover numbers (see How to read this page).

Glycogen storage and mobilisation

• GlycogenPhosphorylase — the reciprocal allosteric pattern is textbook [4]: activated by AMP, inhibited by ATP and by glucose-6-phosphate. Km(Pi) = 5 mM is genuinely millimolar, consistent with the measured phosphate dependence [2]. The specific inhibition/activation constants (and the 15-fold AMP activation) are modelling choices; no exact literature fold-activation was identified. In muscle the switch is phosphorylase kinase, activated by the contraction calcium through its calmodulin (δ) subunit, which converts phosphorylase b to the active a form [44]. The muscle copy's base Vf (0.01) is therefore the resting, kinase-off activity, and a Ca_c activator (half-maximal 0.2 µM, n 2, up to 10×) lifts it as calcium rises with work. At the former un-gated 0.35 it ran ~235 µmol/kg/min against the synthase's ~150 at rest — a futile cycle burning about the whole basal ATP demand, with a net loss of the store; now resting turnover is ~20 µmol/kg/min and the store is stationary. The calcium constants are first-pass modelling choices; the synthase's matching Vf (0.0011) has no literature value. The liver isozyme differs: hepatic phosphorylase is "essentially regulated by phosphorylation" and only weakly AMP-activated (~10–20%), where muscle's is strongly and cooperatively AMP-activated [37], so the liver's copy carries a 1.15-fold AMP activator, and glucagon — the physiological driver of hepatic glycogenolysis through the PKA cascade — activates it (up to 4×) alongside the insulin brake. Post-absorptive tracer studies measure 10–12 µmol/kg body/min (0.75–0.9 mmol/min) of hepatic glucose output. With the liver's switches re-anchored to the post-absorptive rest (below), the resting liver releases ~0.66 mmol glucose/min, the hepatic share of that output. Gluconeogenesis supplies ~50% of that after an overnight fast [43], but the model's hepatic lactate uptake is capped (OPEN-WORK 6.2), so here ~85% comes from glycogen and the store drains ~2% per 10 minutes at rest, ~2× the measured early post-absorptive rate. The gains are modelling choices.
• The muscle's glycogen store starts at 220 mM glucosyl units per liter of muscle cytosol, ~100 mmol per kg of wet muscle — the 1.5–1.8 g/100 g measured in resting human muscle on a mixed diet [45] (it was 80 mM, ~36 mmol/kg, a third of that).
• The liver's carbohydrate switches and the resting state. The hormonal gates on the liver's glycogen phosphorylase and synthase, glucokinase, L-pyruvate kinase, pyruvate dehydrogenase and gluconeogenic enzymes (pyruvate carboxylase, PEPCK, glucose-6-phosphatase, the fructose-2,6-bisphosphate switch, alanine transaminase) were first set treating the resting hormones as the fed state, while the GlucoseSupply stand-in did the post-absorptive liver's job. But the resting body is post-absorptive by every blood measure (glucose 4.5 mM, fatty acids 0.76, ketones 0.12, insulin 33 / glucagon 19 pM). With the gut supply cut, glucose fell to ~2.8 mM within 90 minutes before the liver switched on, which is hypoglycemia, where a real body holds ~4.5 mM for a day. So every insulin half-point on those gates is ×1.3 and every glucagon half-point ×0.625 of its first value: the resting liver now runs the program it previously ran deep in a fast, releasing ~0.66 mmol glucose/min — the liver's ~80–85% share of the ~0.8 mmol/min post-absorptive glucose production (the kidney supplies the rest; GlucoseSupply stands in for it). (First set at ×1.5 / ~0.81 mmol/min; trimmed when the red cell's glucose use fell to its measured rate.) Two missing mechanisms are added: glucagon (PKA) inactivation of hepatic glycogen synthase, the textbook reciprocal of its activation of phosphorylase [4], and stronger glucagon-held GKRP sequestration of glucokinase. The constants remain modelling choices on the model's hormone scale. A fed state (glucose 7–8 mM, insulin several-fold up) is not reachable in the model at all (GlucoseSupply is a homeostat toward 5 mM, and the lumped pancreas's range is compressed), so no lesson depends on these gates' upper half.
• The liver's glycogen store starts at 560 mM glucosyl units per liter of hepatocyte cytosol — the 207 ± 22 mmol per liter of liver measured by ¹³C-MRS after an overnight fast [35], converted to the model's per-cytosol units (~0.35 L of hepatocyte cytosol per liter of liver).
• PhosphoglucoMutase — Keq = 17 (glucose-1-P → glucose-6-P), matching the standard ~17–19 [1].
• GlycogenSynthase now runs the real UDP-glucose route, written out rather than lumped: UGPase (G1P + UTP → UDP-glucose + 2 Pi, the essentially-instant inorganic pyrophosphatase folded in) makes the sugar-nucleotide, GlycogenSynthase itself extends glycogen from it (UDP-glucose → glycogen + UDP), and NucleosideDiphosphateKinase (UDP + ATP ⇌ UTP + ADP, Keq 1, a textbook near-equilibrium phosphotransferase) regenerates the UTP spent, which is where the real "two ATP-equivalents per glucosyl unit" cost actually lands (the first was already spent making G6P). G6P is now correctly modelled as glycogen synthase's allosteric activator rather than doubling as its co-substrate, matching the literature mechanism [3]. Its reciprocal regulation (inhibited by AMP, activated by G6P) is qualitatively literature-grounded [3]. The liver's copy is also activated by insulin and inactivated by glucagon (PKA phosphorylation) [4], so the post-absorptive liver does not store glycogen against its own phosphorylase.

Anaerobic glycolysis

• LactateDehydrogenase_c (pyruvate + NADH + H⁺ ⇌ lactate + NAD⁺) — the equilibrium constant is Keq = 9.0 × 10⁷ mM⁻¹ once the proton is explicit: K = [pyruvate][NADH][H⁺]/([lactate][NAD⁺]) = 1.11 × 10⁻¹¹ M at 38 °C and ionic strength 0.25, as redetermined by Williamson et al. [8] (an apparent ~9 × 10³ at pH 7). It was 3.6 × 10⁸ (apparent 3.6 × 10⁴), which is 4× too high for body temperature — the textbook ΔG°′ of −25.1 kJ/mol is a 25 °C figure and gives 2.5 × 10⁴ [3]; its origin was not traced. The correction lifts the Haldane-derived reverse velocity from 1/72 to 1/18 of forward and lets the liver take up lactate at the measured rate (OPEN-WORK 4.3, 2026-10-08). Km values are within measured ranges [2]; human LDH-A's pyruvate Km at 37 °C is higher (0.38 mM in one assay at pH 7.4) than the model's 0.10, and the model uses one H4-like set for every tissue although muscle and liver are M-rich and the red cell H-rich. They are left alone: the low-lactate reverse flux depends on Vf/(Keq · Km(pyruvate) · Km(NADH)), the lactate and NAD⁺ Kms cancel in it, and no verified human liver activity was found to pair a new Km with. The mild product inhibition by lactate (Ki = 20 mM) is a documented feature [2].

Pyruvate oxidation and the citric acid cycle

Matrix velocities are per-cell values, i.e. the per-liter-of-matrix figure ×10 (see the Overview).

Equilibrium constants (reversible steps)

Set from thermodynamics and consistent with the standard tabulated values [1]:

• Aconitase (citrate ⇌ isocitrate) — Keq = 0.067, favouring citrate ~15:1 [1]
• SuccinylCoASynthetase — Keq = 3.8 [1]
• SuccinateDehydrogenase — Keq = 1.0, set to reflect the near-level succinate flavin / ubiquinone couple (see the ETC section) [5]
• Fumarase (fumarate ⇌ malate) — Keq = 4.4 [1]
• MalateDehydrogenase (malate + NAD⁺ ⇌ OAA + NADH) — Keq = 2.6 × 10⁻⁵, matching the standard ~2.8 × 10⁻⁵ [1]

Regulation of the dehydrogenases

PyruvateDehydrogenase, IsocitrateDehydrogenase, and AlphaKGDehydrogenase are inhibited by NADH (and their acyl-CoA / ATP products) and activated by matrix calcium; isocitrate dehydrogenase is additionally activated by ADP. This pattern matches the literature — the three dehydrogenases are the classic calcium- and energy-charge-sensitive control points [6]. The calcium half-activation (Ka ≈ 1 µM matrix Ca²⁺) is in the measured range for these enzymes [6]. The exact product-inhibition constants (for example the NADH Ki of 0.02 mM) are modelling choices tuned so the resting matrix stays oxidised — faithful in direction and steepness but not taken from a single measured value.

In muscle the products inhibit these dehydrogenases the way they do in the measured enzymes — competitively against the co-substrate they displace (Inhibitor.competes_with: the inhibitor adds (I/Ki)ⁿ to that substrate's binding term, so it senses the product:substrate ratio and the Haldane relationship is unchanged). Acetyl-CoA competes with CoA in pyruvate dehydrogenase (Ki 13 µM against a CoA Km of 7 µM, both from the classic measurement on mammalian — rat heart — PDC [47]); NADH and ATP compete with NAD⁺ in NAD-isocitrate dehydrogenase (ATP I₀.₅ 1.8 mM, bovine heart enzyme [48][49]); NADH competes with NAD⁺ and succinyl-CoA with CoA in 2-oxoglutarate dehydrogenase, keeping the existing Ki values at n 1 where no number was found. No human values were found for these constants. Written as non-competitive Hill-2 brakes they bit roughly ten-fold too hard at physiological ratios: at the muscle's measured resting demand 99.6% of its CoA sat as acetyl-CoA and the cycle only turned through the artificial carboxylase → Cataplerosis loop. Muscle pyruvate dehydrogenase's capacity is also brought to the measured total (fully dephosphorylated) PDC activity of human vastus lateralis, ~3 mmol acetyl-CoA per minute per kg wet [50] — ×0.05 of the shared value, which was ~20× that. With both, the resting muscle matrix holds free CoA ~0.6 mM and NAD⁺/NADH ~5 and the cycle turns on its own. Freed of the over-strong brakes, isocitrate dehydrogenase then drained matrix citrate to ~3 µM, which ran the citrate carrier backwards. The real enzyme holds citrate up through its isocitrate kinetics, which are cooperative: human IDH3 has an isocitrate S0.5 of 2.35 mM (Hill ~2) with no effector, 1.27 mM (Hill ~1.5) with citrate bound, 0.87 mM with ADP and 0.16 mM with both [54]. Matrix citrate is always present and the model has no citrate effector term, so muscle's copy uses the citrate-bound constants (S0.5 1.27 mM, Hill 1.5, through the engine's substrate Hill coefficient, KineticParams.hill, allowed only on irreversible steps), and ADP keeps its existing activator. Matrix citrate now rests ~0.4 mM (physiological). The artificial Cataplerosis drain, sized when the carboxylase loop ran at 58% of citrate-synthase flux, would remove ~80% of the cycle's flux at that citrate, so muscle's copy is cut ×0.02; the carboxylase/ Cataplerosis loop now idles at ~2% of citrate-synthase flux. The liver keeps the shared forms for now: applied there, the competitive forms collapsed its ketogenesis (OPEN-WORK 6.2).

Anaplerosis (a deliberate departure)

• PyruvateCarboxylase — its capacity is cut roughly 60-fold below a generic setting. This differs from a literature enzyme rate deliberately: skeletal muscle carries very little pyruvate carboxylase (it is chiefly a liver/kidney gluconeogenic enzyme) [3], and the model has no cataplerotic exit, so anaplerosis is held minimal to keep the matrix organic-acid pools physiological. The inhibition by matrix malate (Ki = 0.5 mM) is a modelling device with no direct literature counterpart.

Fatty-acid oxidation

Fat reaches the cells as blood fatty acid (FA_b), released by adipose tissue — an artificial stand-in, FattyAcidSupply, gated by insulin (antilipolytic) and glucagon, since the model has no adipose tissue. Both the liver and skeletal muscle burn it through BetaOxidation, which is lumped at the grain of one two-carbon unit: FA_b + CoA + NAD⁺ + FAD → acetyl-CoA + NADH + FADH₂ in the matrix. Its NADH and FADH₂ feed the respiratory chain and its acetyl-CoA the citric acid cycle (or, in the liver, ketogenesis). NAD⁺ and CoA are substrates, so fat oxidation slows itself when the matrix is reduced or its CoA is tied up — respiratory control, and the way acetyl-CoA from fast pyruvate oxidation crowds fat out at high work rates (the role the free-carnitine pool plays in vivo [85]).

Muscle. Resting post-absorptive muscle is mostly a fat-burning tissue: a lean human leg runs at an RQ of 0.83 ± 0.02, ~59% of its energy from fat [81], and the forearm at ~0.75–0.76 [82]. The model's muscle ran on carbohydrate alone (RQ ~0.99) until 2026-10; it now oxidizes blood fatty acid for ~55% of its resting O₂ (RQ ~0.81). Two gates stand in for CPT1 and fatty-acid uptake:

• Insulin, the same CPT1/malonyl-CoA abstraction the liver's copy carries. Hyperinsulinemia with hyperglycemia cuts human leg long-chain fat oxidation by ~80% [83]; the model's pancreas peaks near 90 pM (OPEN-WORK §3.1), where the gate gives ~72%.
• Contraction, a cytosolic Ca²⁺ activator (the phosphorylase-kinase constants, up to 6×) for contraction-induced fatty-acid uptake — CD36 translocation and the fall in malonyl-CoA. The fold is a first-pass choice sized so that working muscle draws no more than the adipose stand-in can supply, and blood fatty acid stays ~0.3–0.6 mM in work. Plasma fatty-acid oxidation then runs at a roughly constant absolute rate from light to hard work, so its share of energy falls with intensity — the pattern measured with tracers [84][85]. Its absolute rate in exercise is below measured, because the model has no intramuscular triglyceride (about half of the fat burned at moderate intensity [84]) and its adipose stand-in has no exercise (catecholamine) signal.

With fat supplying most of the resting muscle's O₂, two of its carbohydrate terms were re-set to the measured rest. The glucose transporter (GlucoseTransport_c_to_b, @muscle) was cut ×0.75 to the measured ~7 µmol/kg/min [42]: resting uptake is transport-limited, so fat oxidation alone cannot lower it. Glycogen synthase was raised ×1.25 so the store is stationary in flux terms; before, it lost ~4.7 µmol glucosyl/kg/min at rest, which the carbohydrate-only muscle oxidized and which, with pyruvate oxidation slowed by fat, would otherwise have left the muscle as lactate. Muscle now takes up ~0.07 mmol/min less glucose than before, so the resting blood glucose set point rose ~2% (4.53 → 4.62 mM) as the liver released a little less by its own hormonal control; the stand-ins were re-anchored to that set point (Scripts/reexpress_standins.py --reanchor --target GLC_b=4.6197).

What it does not fix. Sustained exercise still collapses the muscle — not for lack of fuel any more, but because at exercise turnover the muscle's proton budget does not balance: ATP hydrolysis puts protons into the cytosol faster than the mitochondrial side takes them back, and the cell acidifies steadily even at moderate work with blood lactate below 2 mM (OPEN-WORK §5.4). Muscle also has no contraction-stimulated glucose uptake yet (its transporter answers only to insulin), and matrix acetyl-CoA, though doubled (~0.16 µM), is still far below the measured acetyl-CoA/CoA of ~0.1.

The NADH shuttles

Cytosolic NADH is handed across the inner membrane by two shuttles, both textbook [3]. Their equilibrium constants are set from thermodynamics: cytosolic malate dehydrogenase (Keq = 2.6 × 10⁻⁵) [1], the aspartate aminotransferases (Keq = 0.147, matching the standard ~0.15) [1], and the cytosolic glycerol-3-phosphate dehydrogenase (Keq = 1 × 10⁴) [1].

• The mitochondrial glycerol-3-phosphate dehydrogenase (G3PDH_mito, muscle and liver) hands the two electrons from the DHAP/G3P couple (E°′ ≈ −0.19 V) to a flavin at the ubiquinone/succinate level (≈ +0.03 V) [5] — a ~0.22 V two-electron step, Keq ≈ exp(2 × 0.22 / 0.0267) ≈ 1.4 × 10⁷, so in vivo it runs one way, G3P → DHAP. It was written with Keq 2 and a capacity ~100× the resting shuttle flux, which pinned cytosolic G3P/DHAP to the matrix flavin and over-oxidised both cytosols (muscle NAD⁺/NADH ~9,000, liver ~2,000, against ~725 [8]). With the thermodynamic constant and a capacity cut ×0.01 (a first-pass value; no literature capacity) — halved again once GAPDH's equilibrium constant was corrected (red-cell stage), which restored the triose pools — resting muscle G3P is ~0.27 mM, on the measured ~0.25 in human muscle cytosol [51], with DHAP ~0.3 mM, GAP ~14 µM and no net lactate exchange; its cytosolic NAD⁺/NADH is ~9,600 and lactate/pyruvate ~4 (measured ~10–20; OPEN-WORK 6.2). The later stages let that G3P drift down to ~0.09 mM, and the capacity was cut ×0.25 again (0.005 → 0.00125 per liter of matrix, OPEN-WORK 4.3) when the measured LDH, enolase and PGM equilibrium constants made the same cytosol read more oxidized against a correct lactate/pyruvate equilibrium (pyruvate would otherwise rest at ~264 µM): pyruvate ~99 µM, lactate/pyruvate ~4, NAD⁺/NADH ~2,450 — but G3P rises to ~0.61 mM, 2.4× the measured ~0.25 mM (an intermediate capacity near ×0.4 would sit on it, with pyruvate ~150 µM; interpolated from ×0.35 and ×0.5). The liver's copy is ×0.6 of muscle's per mitochondrion: mGPDH content varies up to ~100-fold between tissues, highest in brown fat, skeletal muscle and brain and lowest in liver, which hands its cytosolic NADH over mainly by the malate–aspartate shuttle [55]. At muscle's capacity (and the liver's 3× mitochondria) it drained the gluconeogenic liver's cytosol to NAD⁺/NADH ~1,900, so reverse-GAPDH stalled and 3-phosphoglycerate piled up. No human activity ratio was found, so the magnitude is calibrated to the measured hepatic NAD⁺/NADH, ~725 [8]: ~960 here, with liver G3P ~0.27 mM (vs ~0.9). With the measured LDH constant the liver takes up lactate at ~170 µmol/kg/min and its oxidation floods the cytosol with NADH (NAD⁺/NADH ~190, the diabetic range of [8]); the liver's capacity was raised ×3 (0.03 → 0.09) to bring it back to ~720 (OPEN-WORK 4.3). That puts it above muscle's capacity per liter of matrix, against the expression ordering [55]: it stands in for the malate–aspartate shuttle, the liver's real route for lactate-derived NADH, which is under-sized here.

• The electrogenic aspartate/glutamate carrier (net one negative charge exported) is what makes the malate-aspartate shuttle effectively one-way; its electrogenicity is well established [5].
• The malate-aspartate carriers and dehydrogenases are scaled to roughly 5 % of a full capacity. This differs from a literature rate by design: skeletal muscle relies chiefly on the glycerophosphate shuttle [3], so the malate-aspartate route is kept minor — which also prevents the matrix dicarboxylate pool from over-filling. The 5 % figure is a modelling choice with no single literature value.

Mitochondrial transport and the adenine nucleotide translocase

• AdenineNucleotideTranslocase — electrogenic ATP⁴⁻/ADP³⁻ exchange (net one negative charge out). Its electrogenicity, and the quarter of the proton-motive force it costs to export each ATP, are literature-grounded [5] and set the P/O ratio correctly [12]. The velocity is a model capacity. In muscle it carries the measured in-vivo ADP control of oxidative phosphorylation, which is at least second order in ADP (Hill ~2.2, half-maximal ~30 µM [46]): an ADP_i activator of that form (up to 10×) on a base capacity ×0.1. The shared form ran far from equilibrium with ~30× the resting flux in its un-activated rate, so at the measured resting turnover it carried the load at ~1 µM free ADP (PCr/Cr ~66): pyruvate kinase and phosphoglycerate kinase starved of ADP, ~40 mM of phosphate parked in 1,3-bisphosphoglycerate/3-phosphoglycerate, and the mitochondria pulled pyruvate from blood lactate. Now resting muscle free ADP is ~7 µM (calibrated ³¹P-MRS ~14 µM [23]), PCr/Cr ~7, free Pi ~3.8 mM.
• PyruvateCarrier — electroneutral proton symport, the established mechanism of the mitochondrial pyruvate carrier [9]. Its capacity is reduced about threefold from a naïve setting; this differs from a literature rate deliberately, so the mitochondria do not drain cytosolic pyruvate to near-zero and prevent lactate dehydrogenase engaging under heavy demand.
• PhosphateCarrier — modelled with two protons per phosphate, where the literature usually gives one [5]; see the ETC modelling-choices note for why.
• MatrixProtonHomeostat — a single electroneutral proton exchange holding the matrix ~0.4 pH units alkaline. It is a lumped stand-in for the aggregate K⁺/H⁺ and Na⁺/H⁺ antiporters [10], so it has no single literature rate; the 0.4-unit gradient is set below the ~0.5–0.7 often quoted [5] so more of the proton-motive force sits in the membrane potential.
• OM_* (outer-membrane porins) — fast, near-equilibrating exchange reflecting the freely permeable outer membrane [5]; the large velocity is deliberate, not a measured rate.
• AdenylateKinase_c / _m (2 ADP ⇌ ATP + AMP) — Keq = 0.44 (written as its reciprocal, 2.27), which matches the standard value [7]; its near-equilibrium operation is what makes AMP a sensitive energy-stress signal.

Calcium signalling

Calcium is the feed-forward matching mitochondrial output to demand ("parallel activation"), a well-established mechanism [6].

• CalciumUniporter — the membrane-potential-driven MCU (net two positive charges in). Its low calcium affinity — it engages in the micromolar range — is literature-grounded [6]; the exact Km and velocity are model capacities.
• CalciumEffluxMito (lumped NCLX / mHCX) and CalciumReuptake (SERCA-like) — lumped devices with no single literature rate, sized to hold resting cytosolic calcium near 0.1 µM and matrix calcium near 0.2 µM, the measured resting levels [3].

The phosphocreatine buffer

• CreatineKinase_c — the apparent equilibrium constant near 150 at pH 7 (represented as Keq = 1.5 × 10⁶ once the proton is explicit) matches the standard value [7]. Km(PCr) = 0.72 mM and Km(ADP) = 0.035 mM are within measured ranges [2]. The high velocity reflects the enzyme's fast near-equilibrium buffering — a literature-grounded property [3] — though the exact velocity is a model capacity.

Lactate export and the blood compartment

• LactateTransport_c_to_b — monocarboxylate transport carrying one proton per lactate, the established MCT mechanism [9]; exporting lactate is therefore also how a working muscle exports acid. Km ≈ 1 mM is broadly consistent with reported MCT affinities [9].
• BloodLactateConsumption — an artificial systemic sink standing in for lactate disposal by other tissues (the Cori cycle). It is a boundary term rather than an enzyme, so it has no literature rate by construction.
• BloodLactateProduction — an artificial systemic source standing in for the constitutive resting glycolysis of the unmodeled tissues (gut, skin, renal medulla, brain), which hold circulating lactate near ~1 mM at rest [3]. Self-inhibited at that set point (so it is off during exercise) and acid-neutral (it carries the proton the disposal sink removes). A boundary term, so it has no literature rate by construction; the set point it targets is the measured resting arterial lactate (0.5–1.5 mM). The red cells, once its largest share, are now modeled explicitly at full mass, so its rate was reduced by the share they (and the full-mass muscle) now supply — see Whole-body scaling below.

Whole-body scaling: tissue mass and the shared blood pool

Each registered tissue represents the whole of that tissue in a reference adult, not a sample of it. The shared blood compartment stands for 14 L of extracellular fluid — plasma plus interstitial fluid, the space glucose, lactate, ketones and the hormones actually distribute through — chosen inside the 11.7–17.3 L range for the reference adult male [28]. A tissue's blood weight (mass_factor) is its whole-body intracellular water divided by that volume:

• Skeletal muscle — 29 kg [28] × 0.65 L intracellular water per kg (resting human muscle carries ~0.76 L water/kg, ~0.08–0.11 of it extracellular [29]) = 18.85 L → 1.346.
• Liver — 1.8 kg [28] × 0.50 L/kg = 0.90 L → 0.0643. The water figure is a modelling estimate: liver is ~0.71 L water/kg with ~0.20–0.25 sinusoidal + Disse space, and hepatocytes are ~78% of the parenchyma [31]; no single human table was found.
• Red cells — 2.3 L of cells [28] × 0.717 L water per L of cells [30] = 1.65 L → 0.118. All of that water is cytosol (no organelles), not the reference 70%, so the red cell's cytosol-homed velocities act over all of it (cytosol_volume_scale 1/0.70).

The liver also has its own mitochondrial density: its intermembrane space and matrix are 3× the reference (muscle) geometry at the same cytosol, so mitochondria fill 28% of the modeled hepatocyte — within the 22–28% measured by stereology (rat [39][31]; human biopsies show no principal difference [40]) — against ~5% in human vastus lateralis [41]. Matrix velocities are per liter of matrix, so this is 3× the mitochondrial capacity per liter of cell water (more mitochondria, each like muscle's); it is what lets the liver carry its literature oxygen use at a physiological membrane potential. The 3× is a modelling choice within the measured range.

This is a mass share, not a blood-flow share: the model's blood pool is well mixed, so exchange is limited by transporter and enzyme capacity, which scales with cell water. (The liver receives ~25% of resting cardiac output against muscle's ~17% [28], which would matter only where exchange becomes flow-limited — not modeled.) When the factors were set to these values (replacing a hand-set muscle 1.0, liver 0.1, red-cell 0.008), every systemic stand-in — GlucoseSupply, BloodLactateProduction, FattyAcidSupply, GlycerolSupply, AlanineSupply, the two ketone disposals, OxygenSupply, CO2Removal, BloodAcidBaseRegulation — was re-expressed by exactly the share of the blood budget the modeled tissues now cover, so the resting state is unchanged. These are modelling devices, not measured rates. Each tissue's per-kilogram rates come from its per-liter capacities and are being calibrated against whole-organ measurements tissue by tissue. The liver is done: resting O₂ use ~1,230 µmol/kg/min against ~1,300 (≈200 kcal/kg/day [32]); resting (post-absorptive) glucose output ~0.66 mmol/min — its ~80–85% share of the measured 0.75–0.9 total — with glucose cycling ~21% against 14% [34]. After that change the stand-ins were re-anchored (each rescaled until the settled rest returned to the previous blood set points) rather than re-expressed, because the liver's blood pull changed through its kinetics, not its mass. The muscle is done too: resting O₂ use ~75 µmol/kg/min against ~85 (13 kcal/kg/day [32]); ATP turnover ~0.0082 mM/s against 0.008 [33]; glucose uptake ~9 µmol/kg/min at rest against ~7 for resting legs [42] (the rest needs muscle fat oxidation, not yet modeled); glycogen and matrix citrate stationary; no resting lactate export. The brain's glucose use moved into its own stand-in (BrainGlucoseUptake) in the same change, and the stand-ins were re-anchored again. The red cell is done: glucose ~16.7 µmol/kg/min against ~18–23 (1.2–1.5 µmol/mL cells/h), lactate ~1.9× glucose, a true steady state (it previously used ~3.7× its glucose and never settled).

Proton buffering and pH regulation

• Intracellular pH is tracked implicitly: each of the cytosol, intermembrane space, and matrix carries its total titratable proton as the state variable, and pH is derived each step by inverting the compartment's buffering — a generic buffer (pKa ≈ 7.3, ≈ 51 mmol H⁺ per pH unit per liter, at the upper edge of the 30–50 range reported for muscle [3]) plus a binding polynomial for every phosphate species (Pi pKa₂ ≈ 6.8, the ester phosphates ≈ 6.1–6.5). This is the standard mechanistic-model treatment [Beard/Bazil] and is what lets a reaction's fractional proton (e.g. glycogen phosphorylase releasing ≈ 0.29 H⁺ as it converts Pi to glucose-1-phosphate) fall out of the chemistry rather than being dropped by integer stoichiometry. No separate tracking term is used for it (see the proton and charge stoichiometry above).
• ProtonBuffer_b — the blood buffer stays an explicit reversible buffer at pKa ≈ 7.1, a bicarbonate-weighted value, sized to ~24 mmol titratable base so plasma holds near pH 7.4 and acidifies only modestly, consistent with measured blood buffering [3].
• PlasmaProtonHomeostat — the plasma-membrane Na⁺/H⁺ exchanger, anion exchanger, and bicarbonate cotransporters, lumped into one electroneutral proton exchange that holds each cell's cytosol ≈ 0.4 pH units acid of blood, the direction and magnitude of measured resting cytosol-to-plasma pH gradients [3]. A model term, not one enzyme.
• BloodAcidBaseRegulation — the lungs' and kidneys' export of the net metabolic acid-base load, holding blood toward its set point. A boundary term standing in for respiratory + renal compensation, so it has no single literature rate by construction. It is a two-way homeostat (declared Keq = the set-point proton concentration): a source when blood is more alkaline than the set point, a sink when more acid. It once answered the liver's alkalinizing proton residual, and then — when that shrank — a standing acid load, which it removed at rest with the resting blood pH ~7.36 below its 7.40 set point. That standing load was the integer-proton errors corrected in OPEN-WORK 5.4 (see the proton and charge stoichiometry); with them gone the body is proton-neutral at rest, the term idles there, and its set point sits at the pool's resting value (4.445e-5 mM; blood rests at pH 7.356, a venous-pool value — setting it to 3.98e-5, pH 7.40, rests blood at 7.40 and the cytosols at 7.00 with nothing else changed). As a stand-in it absorbs whatever small standing proton load the placeholders leave: the set point moved 3.98e-5 → 4.396e-5 with the exercise proton balance and → 4.445e-5 when the ketone disposals, NADPH sinks and AMP recoveries began consuming a proton (OPEN-WORK 5.1).
• Exercise acid-base behavior. Below the critical power, muscle pH is held within minutes and stays flat (³¹P-MRS: stable within about three minutes of onset), while above it PCr keeps falling and pH falls progressively until exhaustion [88]. ATP turnover that mitochondria regenerate accumulates no net acid; acidosis comes from ATP use outrunning mitochondrial regeneration, with the acid delivered through glycolysis and PCr rather than by lactate production itself [89]. Muscle removes the acid mainly by lactate–H⁺ cotransport and Na⁺/H⁺ exchange against intracellular buffering [90]. The model (headless, from the settled rest, muscle ATPConsumption as set): at 0.2 mM/s (moderate) the cytosol rises from 6.96 to 7.02–7.03 within five minutes and stays there for the first 40 minutes (7.01 at 60 minutes as phosphocreatine runs low), blood pH holds 7.41–7.43 and lactate ~1.2 mM; at 0.5 mM/s (hard, above the critical power) the cytosol falls progressively 7.08 → 6.80 over 15 minutes, blood lactate climbs to ~16.6 mM and blood pH to 7.18, and muscle ATP holds at 6.7 mM. The ~0.07 pH rise at the onset is the proton consumed as creatine kinase rebuilds ATP from phosphocreatine (the model's PCr buffer, which is spent within minutes at the hard demand). Before OPEN-WORK 5.4 the same moderate demand acidified the cytosol to 6.70 in 20 minutes and, at the hard demand, ATP collapsed within 15 minutes.

Boundary conditions: supply, demand, and gas exchange

These are source/sink terms representing the cell's environment, not enzymes.

• ATPConsumption — the basal ATP-demand rate, Vf = 0.012 mM/s per liter of muscle cytosol, which at rest is ~0.0082 mM/s per liter of cell water, matching the measured resting ATP turnover of human skeletal muscle, 0.008 ± 0.002 mM/s (0.007–0.013 across muscles, from the rate of phosphocreatine use during resting ischemia) [33]. With the model's P/O and ~20% proton leak it gives resting muscle O₂ use ~75 µmol/kg/min (~85 measured, 13 kcal/kg/day [32]). It was 0.026 (and an earlier version of this page wrongly gave the measured range as ~0.02–0.05 mM/s), ~3× the measured turnover, which drove resting muscle O₂ to ~2.3× the measured rate. The guided exercises override this with their own workloads. The liver has its own basal demand, Vf = 0.27 mM/s, sized from the liver's measured resting energy use — ~200 kcal/kg/day [32], ~1,300 µmol O₂/kg/min, which at a P/O of ~2.5 is ~5–6 mmol ATP/kg/min — and so matching the literature at that derivation; it was muscle's 0.026, which left the liver respiring at a third of its measured rate. In muscle this term co-releases 0.05 Ca²⁺ per ATP as the contraction signal; the liver's copy co-releases 0.023 per ATP, a lumped resting calcium source calibrated so hepatocyte cytosolic Ca²⁺ rests at ~0.22 µM, the level measured in primary human hepatocytes [36] (hormone-driven hepatic Ca²⁺ signalling is not modeled).
• GlucoseSupply — a gentle bidirectional homeostat on blood glucose (declared Keq = 5 mM, the resting blood-glucose set point), lumping gut absorption and the whole-body glucose handling the model does not resolve. Its rate is a modelling device with no literature value, re-expressed for the full-mass tissues and re-anchored after the liver's and the muscle's per-kilogram recalibrations (see Whole-body scaling). Since the liver's switches were re-anchored to the post-absorptive rest, the liver supplies the resting body's glucose itself, and this term is a ~0.05 mmol/min remainder. In vivo that is the kidney's ~0.1–0.15 mmol/min post-absorptive output, net of the unmodeled tissues' use. Guided exercises set their supply as a fraction of this default.
• BrainGlucoseUptake — an artificial stand-in for the unmodeled brain, to be retired when a brain tissue is registered. The brain is the body's largest glucose consumer at rest and keeps consuming through a fast: ~31 µmol/100 g/min by the Kety–Schmidt method [52] and ~0.25 µmol/g/min by PET [53], ~0.4 mmol/min for the 1.45 kg reference brain [28]. Its uptake is insulin-independent (GLUT1 at the blood–brain barrier, GLUT3 in neurons) and holds roughly constant across the normal glucose range, so it is a Michaelis–Menten sink on blood glucose with no hormone gate, sized to ~0.4 mmol/min at the resting ~4.5 mM (Km 1 mM is a first-pass choice). It was formerly hidden inside GlucoseSupply's net; split out, cutting the dietary supply no longer also switches the brain off.
• OxygenSupply — a boundary gas-exchange term. Oxygen delivery is self-limited so matrix O₂ settles near 0.012 mM, within the measured mitochondrial range of 0.005–0.03 mM [5]; the delivery rate itself is a boundary condition, not a measured enzyme rate (re-expressed for the full-mass tissues, then re-anchored when the liver's and the muscle's oxygen use were brought to their literature rates). Its ceiling (Vf, reached as blood O₂ runs low) is set to 25× its resting supply: a real body raises oxygen delivery ~10–13× from rest to VO₂max (an untrained adult man's ~35–45 mL/kg/min) with arterial O₂ content held near rest, nearly all of the rise going to working muscle, and this supply covers only the modeled tissues (~4.4 of a whole-body ~11 mmol O₂/min at rest), so 25× (~110 mmol/min) is VO₂max less the unmodeled tissues' share. Its self-inhibition constant is solved so the resting supply is unchanged, with a steep first-pass gain (Hill 6) so blood O₂ stays near its set point as delivery rises. At the old ~3× ceiling, whole-body exercise drained blood O₂ to ~11% of rest and the liver went anoxic. Each tissue then draws on the blood through its own OxygenUptake (an artificial capillary-delivery stand-in); muscle's is sized ×4 so its transport does not bind before this whole-body ceiling does (~4.1 mmol O₂/kg/min at the blood O₂ of hard exercise; whole-body delivery averages ~3.7 over all muscle at VO₂max, against a mitochondrial capacity of ~6 and ~13–18 in fully perfused knee-extensor muscle [Andersen & Saltin 1985]), with its self-limit re-solved so its resting uptake is unchanged.
• CO2Removal — a boundary gas-exchange term, made a bidirectional homeostat that holds dissolved blood CO₂ at its set point (declared Keq = 1.2 mM). This is the dissolved arterial CO₂ at pCO₂ ~40 mmHg (40 mmHg × 0.03 mmol·L⁻¹·mmHg⁻¹ = 1.2 mM) [14]; the model has no bicarbonate pool, so CO2_b is the dissolved/metabolic CO₂ (~5% of total blood CO₂), not the ~24 mM total-CO₂/bicarbonate. It lumps whole-body respiration and ventilation, standing in for respiratory control, so it has no single enzyme rate.
• PhosphateSupply — a lumped homeostat standing in for the sodium-phosphate cotransporter and whole-body phosphate regulation. It is a placeholder device with no single literature rate.
• AMPRecovery_c / _m, NADHConsumption, FADH2Consumption — surrogate source/sink terms (the last two default to off). They are modelling devices, not measured reactions.

Starting concentrations

The literature starting values are measured resting-skeletal-muscle values, and match the literature [11][3]. They are the anchors: they fix every conserved pool's total (adenine nucleotides, NAD(H), NADP(H), CoA, creatine, the uridine and glutathione pools, the blood buffer) and the glycogen stores. A run then starts from where the model itself settles with those totals (App/resting_seed.py, generated by Scripts/seed_resting_state.py), so how each total splits, and the fast intermediates no measurement fixes in every tissue, are model outputs rather than inputs:

• ATP 8 mM, phosphocreatine 30 mM, creatine 10 mM, cytosolic NAD⁺ 0.7 mM, free phosphate 3 mM [11]; glycogen 220 mM glucosyl units per liter of cytosol (~100 mmol/kg wet muscle [45]).
• Free ADP (0.015 mM) and AMP (0.002 mM) are set far below total cellular content on purpose: most adenine nucleotide is protein-bound, and the low free concentrations are what enzymes sense — a literature-grounded distinction that makes AMP a sensitive stress signal [3].
• Matrix nucleotides are seeded at ATP/ADP ~29 (much lower than the cytosol, because the electrogenic translocase drives export) [5] and NAD⁺/NADH ~5, both consistent with measured mitochondrial poise [8].
• Resting cytosolic calcium 0.1 µM, matrix calcium 0.2 µM, and blood pH 7.4 are standard resting values [3].
• Where the settled rest departs from measurement (the residuals in OPEN-WORK §4.1 and §6.2, now visible from the first moment of a run rather than after its first hour): muscle matrix ATP/ADP ~2,600, above the cytosol's, because the translocase carries all of the ADP control; muscle cytosolic NAD⁺/NADH ~10,000 and lactate/pyruvate ~4 (measured ~700 and ~10–20) — the over-oxidised cytosol runs cytosolic malate dehydrogenase backward, so oxaloacetate rests at ~0.12 mM and aspartate aminotransferase converts nearly all cytosolic glutamate to aspartate (glutamate ~1 µM, measured ~2–6 mM); matrix acetyl-CoA ~0.16 µM (doubled once muscle began burning fat, still far below the measured acetyl-CoA/CoA ~0.1) and succinate/fumarate sub-µM.

Tissue health thresholds

The Body tab's Tissue health page reads each tissue's health markers against danger ranges and classifies the tissue as healthy, stressed, dying or dead (the shared bloodstream as healthy, stressed or critical; blood cannot die). The ranges and the classification are in App/ui_qt/tissue_health_content.py, and this section must change in the same commit as they do. They are not model parameters: nothing here feeds back into the simulation, and the model is never tuned to satisfy them.

The ranges mark real danger, not "outside the textbook normal range". The model has resting residuals that sit outside measured ranges without being dangerous: muscle's over-oxidized cytosol (OPEN-WORK §6.2), the liver's ~135 mV membrane potential, the red cell's raised pyruvate (~0.6 mM), its NADPH/NADP of ~0.26 and its slowly creeping oxidized hemoglobin. The default resting body reads healthy everywhere. Human data are used first; where a value is from animals or is a modeling choice, it says so.

"% of rest" is measured against each tissue's own settled resting value, the one every run starts from (App/resting_seed.py). For example, muscle ATP is 8.0 mM, liver ATP 5.0 mM and red-cell ATP 1.73 mM. The literature supplies the fraction, not an absolute.

| Marker | Tissues | Stressed | Danger tier (dying / critical) | Basis | |---|---|---|---|---| | ATP | muscle, liver, red cell | < 60% of rest | < 25% of rest | A maximal 30-s sprint leaves human muscle ATP at 70.5 ± 6.5% of rest [58], so below 60% is past healthy exhaustion. Graded ATP depletion kills cells; below ~15–25% of control the death is necrotic, and it comes faster the deeper the depletion [60] (mouse proximal tubule; no human threshold found). Human T cells show the same switch from apoptosis to necrosis when ATP is depleted, but no single threshold is reported [61]. | | Phosphocreatine | muscle | < 15% of rest | — | A maximal 30-s sprint leaves 19.7 ± 1.2% [58] and 16.9 ± 1.4% [59]. Below 15% the ATP buffer is spent. Depletion is normal in hard exercise, so this is stress only. | | Membrane potential (Δψ) | muscle, liver | < 100 mV | — | FIRST-PASS, derived. Intact cells hold Δψ ~150–180 mV [5]. Holding a resting phosphorylation potential of ~55–65 kJ/mol at 8/3 + 1 protons per ATP [20] (bovine c8 ring) needs a proton-motive force of ~150–175 mV. Even with a matrix ΔpH of ~50 mV, a Δψ below ~100 mV cannot sustain it, so the synthase stalls or runs in reverse. The threshold sits clear of the liver's ~135 mV resting residual (OPEN-WORK §4.1). | | Cytosolic pH | muscle, liver, red cell | < 6.5 | — | After maximal exercise to exhaustion, human muscle pH reaches 6.6–6.4 [63], and 6.69–6.72 after a 30-s sprint [58][59]. Below 6.5 is the acidosis of exhaustion; it is stress only, since the tissue's fate is read from its energy. Intracellular pH is solved from the compartment's total titratable proton (MetabolicModel.compartment_pH). | | Reduced glutathione (GSH) | muscle, red cell | < 50% of rest | < 10% of rest while H₂O₂ > 100 nM | In Beutler's glutathione-stability test, the GSH of normal red cells is virtually unaffected by an oxidant challenge, while that of G6PD-deficient ("drug-sensitive") cells falls markedly [64]; the 50% cut is a FIRST-PASS reading of that contrast. Depletion alone is survivable: rat hepatocytes held below 5% of control GSH kept their viability until ATP also fell [65] (rat). So low glutathione is the danger tier only under peroxide load, when oxidation goes unopposed. | | Cytosolic H₂O₂ | muscle, red cell | > 100 nM | (with GSH, above) | Physiological signaling runs at ~1–10 nM; above 100 nM is oxidative distress [66]. Matrix H₂O₂ is not used: it rests at ~0.2 µM, a calibration level above this line. | | Oxidized hemoglobin (share of total) | red cell | ≥ 10% | ≥ 50% | Clinical methemoglobin bands [67]: cyanosis at 10–20%, seizures and coma at 50–70%, and death possible above 70%. The red-cell compartment is the whole red-cell mass, so its oxidized share reads as a whole-blood level. | | Glucose | blood | < 3.0 or > 13.9 mM | < 2.3 or > 33.3 mM | Level 2 ("clinically significant") hypoglycemia is below 3.0 mM [68]. Cognitive impairment begins at ~2.8 mM, and coma has been reported at 2.3–2.7 mM [69]. 13.9 mM (250 mg/dL) and 33.3 mM (600 mg/dL) are the glucose criteria of diabetic ketoacidosis and of the hyperosmolar hyperglycemic state [70]. | | pH | blood | < 7.20 or > 7.55 | < 7.00 or > 7.65 | Severe acidemia (pH < 7.20) carried 57% ICU mortality [72]; pH < 7.00 carried 67.5% [73]. In alkalemia, mortality was 41% at 7.55–7.56 and 80% at 7.65–7.70 [74] (as tabulated in later reviews), and 48.5% above 7.60 [75]. | | Lactate | blood | > 4 mM | — | An initial lactate ≥ 4 mM was independently associated with mortality in severe sepsis (OR 4.87) [76]. Hard exercise reaches far higher levels without harm, so lactate is stress only; the danger is the acidemia, read from pH. | | Ketones (β-hydroxybutyrate + acetoacetate) | blood | > 3 mM | — | Ketonemia ≥ 3.0 mM is the ketoacidosis criterion [71]; fasting ketosis stays below it. | | O₂ | blood | < 50% of rest | < 10% of rest | FIRST-PASS, not literature. The model's blood O₂ is one well-mixed extracellular pool (between arterial and venous), so clinical PaO₂ cut-offs cannot be applied to it; at rest it already sits where a PaO₂ scale would call hypoxemic. These bands flag a failing supply. The 50% line is loosely anchored to human data: healthy conscious volunteers cut from 14.0 to 7.3 mL O₂/kg/min of delivery (about 52% of normal) by hemodilution plus a β-blocker showed no rise in lactate and no change in O₂ use, so their critical delivery is below that [91]; a pooled concentration is not a delivery, so the line stays FIRST-PASS. Hard exercise dips the pool to ~58% of rest and does not trip them; a cut supply does. |

Statuses. A tissue is stressed when any marker is outside its safe range. It is dying when a marker is in its danger tier: ATP below 25% of rest, glutathione below 10% under peroxide load, or half the hemoglobin oxidized. It is dead when its ATP has stayed below 10% of rest, without a break, for as long as the real tissue survives an energy collapse, or (red cell) when 70% of its hemoglobin is oxidized. Cells survive an energy collapse for a while, because the damage that makes it irreversible (sodium and calcium loading, swelling, membrane failure) takes time, and how long differs by tissue:

| Tissue | Death clock (ATP below 10% of rest) | Basis | |---|---|---| | Liver | 60 min | Hepatic ATP is depleted within ~10 min of warm ischemia [78] (rat), yet a non-diseased human liver tolerates continuous normothermic ischemia for at least 60 min (up to 85 min, with no chronic damage on biopsy) [77]; rat livers recover after 35 min of ischemia but only partly after 65 [78]. | | Skeletal muscle | 60 min, FIRST-PASS | Ischemic muscle keeps its ATP for the first ~2–3 h on phosphocreatine and glycogen; necrosis then rises from 2% at 3 h to 30% at 4 h and 90% at 5 h of complete ischemia [79] (dog). An hour of deep ATP depletion falls within that window. | | Red cell | 12 h, FIRST-PASS | Human red cells incubated without glucose fall below ~15% of their ATP after ~10 h and are rigid spheres, no longer filterable, by ~24 h [80] (in vitro; rigid cells are cleared by the spleen). | | Any other tissue | 30 min | Severely ischemic myocardium is irreversibly injured after 20–40 min, as its ATP falls below ~10% of control [62] (dog; no human data exist). |

The model's ATP collapses faster than real tissue's, because its ATP demand does not slow as ATP falls (OPEN-WORK §10): the liver's falls below 10% about 70 s after its oxygen is cut, where a real liver's takes ~10 min. The clock therefore starts at the model's own crossing. Until it runs out, a tissue with collapsed energy reads dying. (A first version used a 60-s clock and declared death ~50× too soon.) The bloodstream's danger tier is critical; blood never reads dead.

Death latches for the rest of the run. The model has no irreversible damage. With no fatigue on the ATP demand (OPEN-WORK §10), an unfuelable demand runs ATP to ~0, and a scheduled lower demand brings the chemistry fully back. A real tissue would not come back, so the page keeps the tissue dead and says that the model's chemistry has recovered but a real tissue would not. Stressed and dying are live; a tissue that recovers shows when it was in trouble (for example, "Recovered: was stressed 1:35–4:20").

Markers left out:

• Energy charge moves in lockstep with ATP here, and its 0.8 benchmark is not a human danger threshold.
• Cytosolic Ca²⁺ is co-released with the ATP demand and cleared to an infinite reservoir without consuming ATP (OPEN-WORK §10), so it cannot build up from energy failure and would only flag hard work.
• Matrix pH rests ~0.5 below measurement (the 2-H⁺ phosphate carrier, OPEN-WORK §10).
• NADPH/NADP rests at ~0.26 in the red cell.
• Liver oxidative markers: the liver has no glutathione in the model.

What a 2026-10-08 literature pass found for the FIRST-PASS cut-offs (OPEN-WORK §8.3; the constants did not change). Δψ: no absolute millivolt threshold for intact human cells turned up — membrane-potential dyes (TMRM, TMRE, JC-1) report relative loss — so the derived 100 mV line stays. Blood O₂: no universal human venous-PO₂ cut-off turned up, so only the delivery anchor above could be added. Muscle death clock: no human ATP timeline for ischemic muscle turned up, so the 60-minute clock (from dog ischemia) cannot be re-derived. GSH line: Beutler's percentage cut-offs are in a 1957 paper that could not be read, so the 50% line stays a reading of the qualitative contrast.

Readings in the reference scenarios (headless, from the settled rest; re-verified 2026-10-07 after the exercise proton balance, OPEN-WORK §5.4 — the hard-exercise and recovery rows changed because the muscle now survives its work — and again 2026-10-08 after the LDH, enolase and PGM equilibrium constants, OPEN-WORK §4.3: only the hard-exercise timings moved, by 3–7 s, read on a 1-s grid):

| Scenario | Muscle | Liver | Red cell | Bloodstream | |---|---|---|---|---| | Rest, 90 min | healthy | healthy | healthy | healthy | | Guided oxygen exercise, Anaerobic preset (300 s) | stressed from 0:50 (Δψ ~77 mV) | dying from 0:50 (the preset cuts the whole-body O₂ supply; ATP < 10% from ~1:10) | healthy | critical from 0:15 (O₂) | | Hard exercise (muscle demand 0.5 mM/s, 900 s) | stressed 1:37 (PCr), never dying (ATP holds 6.7 mM) | healthy (ATP 5.0 and Δψ 136 hold) | healthy | stressed 3:28 (lactate, peak 16.3 mM), pH under 7.20 from ~13:50 (lowest 7.19); never critical | | Whole-body O₂ cut (1800 s) | stressed from 2:05 (Δψ) | dying from 0:50 (dead at ~1:01, past the run's end) | healthy | critical from 0:20 | | Favism, G6PD-deficient + fava (1200 s) | healthy | healthy | stressed 2:20, dying 4:00, dead 14:40 (hemoglobin 70% oxidized) | healthy | | Favism, healthy + fava; muscle backup on | healthy | healthy | healthy | healthy | | Muscle NADPH backup off (1200 s) | stressed 7:00, dying 10:35 | healthy | healthy | healthy | | Strong uncoupling (600 s) | stressed from 0:05 (Δψ 63–85 mV, PCr ~9% at 10 min; ATP holds ≥ 91%) | healthy | healthy | healthy | | Hard exercise 4 min, then demand 0.012 | stressed 1:37, healthy from 4:14 | healthy | healthy | stressed 3:28–6:01 (lactate), then healthy (lowest pH 7.35) |

References

Literature audit of the current model

This audit is a snapshot of the model definitions present in the repository on 1 October 2026. It is documentation only: no value, equation, reaction, initial condition, compartment, model file, or simulation path was changed. It was updated the same day for the full-mass tissue change (the whole-body scaling constants and the re-expressed systemic stand-in velocities below), and again for the liver's per-kilogram recalibration (OPEN-WORK 6.2, liver stage: its mitochondrial density, basal ATP demand, glucokinase, phosphorylase and pyruvate dehydrogenase gates, glycogen store, and the re-anchored stand-ins). It was updated on 3 October 2026 for the muscle's (OPEN-WORK 6.2, muscle stage: its basal ATP demand, phosphorylase-kinase calcium gate, glucose transporter, translocase ADP control, competitive dehydrogenase inhibition and PDC capacity, human IDH3 isocitrate kinetics and the muscle's Cataplerosis drain, glycogen store, the shared mitochondrial glycerol-3-phosphate dehydrogenase, the new BrainGlucoseUptake stand-in, and the re-anchored stand-ins), and again the same day for the liver follow-up (its carbohydrate switches re-anchored to the post-absorptive rest, glycogen synthase's glucagon brake, its lower mitochondrial glycerol-3-phosphate dehydrogenase, and the re-anchored stand-ins), and again for the red cell's (OPEN-WORK 6.2, red-cell stage: its measured enzyme activities, the erythrocyte isozymes' regulation, its all-cytosol geometry, the corrected GAPDH equilibrium constant, the re-calibrated mitochondrial G3P dehydrogenase, the liver re-anchor trimmed to ×1.3, and the re-anchored stand-ins). It was updated on 8 October 2026 for the measured lactate dehydrogenase, enolase and phosphoglycerate mutase equilibrium constants (OPEN-WORK 4.3): the three constants, the muscle's and the liver's mitochondrial G3P dehydrogenase capacities, and the re-anchored stand-ins.

Repository traceability and audit scope

• Reactions, stoichiometry, Vf, Vr, Keq, Km, inhibitors, activators, Hill coefficients, charge terms, and special electron-transfer settings are defined in App/metabolism_models/*.py.
• App/metabolism_types.py defines the rate laws, Haldane-derived reverse velocities, Butler-Volmer/Marcus electron-transfer law, compartment-volume conversion, membrane-potential coupling, phosphate proton binding, and the global buffer constants.
• App/fluxion_core.py assembles the skeletal-muscle, liver, and erythrocyte models and defines their metabolite lists and initial conditions. App/tissue_registry.py applies tissue namespaces, scalar overrides, tissue-specific regulators, mass factors, and per-tissue compartment volumes.
• Display units are defined in App/ui_qt/model_data.py: concentrations are mM unless explicitly identified otherwise; mitochondrial potential is mV and insulin/glucagon signals are pM. Simulation time is seconds. Intracellular H_* states are total titratable-proton equivalents, not free proton concentrations; blood H_b remains an explicit free-proton concentration.

The assembled default model contains 235 reaction instances and 220 starting state values across skeletal muscle, liver, erythrocyte, and the shared blood pool. Tissue-tagged copies are retained as separate audit targets; the compact register below combines only copies whose entire displayed parameter bundle is identical.

The comparison count is by evaluation statement, not by paper and not by reaction. A reaction can therefore contribute several conclusions (for example, stoichiometry matches, Keq matches, Vf is not directly comparable, and its generic Km set has insufficient assay context). Across 1,306 evaluation statements, the conservative status totals are:

• Matches literature — 216
• Does not match literature — 4
• Not directly comparable — 564
• No reliable literature value found — 101
• Insufficient context — 421

How the comparison labels were assigned

Vf is a model capacity (or, for complexes I, III and IV, an exchange-current scale), not kcat and not an enzyme concentration. The register therefore marks every Vf and every Haldane-derived Vr as Not directly comparable, unless the reaction is an artificial boundary or recovery term for which No reliable literature value found is more informative. A matching Km does not validate Vf; a matching transformed equilibrium constant does not validate the chosen rate law. The kinetic-database comparison used BRENDA and SABIO-RK [17][18], but most Fluxion entries omit organism, isoform, free Mg²⁺, pH, temperature, ionic strength, enzyme concentration, and assay direction. Those numerical Km, Ki, Ka, and Hill terms are conservatively marked Insufficient context unless a close primary or curated match was available.

Chemical Keq values were compared as written, with explicit-proton reactions kept distinct from apparent transformed K′eq values. eQuilibrator [1][15] and the component-contribution framework [16], together with Rhea [19], were used for reaction identity and thermodynamic direction. This avoids treating chemical concentrations as activities or silently converting a pH-7 transformed constant into the explicit-H⁺ convention used by several Fluxion reactions.

High-confidence findings

• The reversible glycolytic constants, malate dehydrogenase, aminotransferase, adenylate kinase, creatine kinase, TCA reversible steps, respiratory midpoint- potential-derived constants, and ATP-synthase 8/3 H⁺ per ATP are supported at the level claimed, subject to the chemical-versus-transformed convention stated above [1][7][15][20].
• The respiratory-chain total of ten pumped charges per NADH and the resulting theoretical P/O near 2.7 are consistent with the bovine c8 ATP-synthase structure; measured mammalian P/O is lower (about 2.1–2.5 depending on preparation and workload), as expected when leak and transport costs are included [12][20][22].
• Matrix Ca²⁺ half-activation at 0.001 mM (1 µM) with about two-fold activation is close to the 0.84 µM, approximately two-fold response measured at 37 °C in isolated skeletal-muscle mitochondria [21]. It is not evidence that every individual enzyme has the same Ka or Hill coefficient.
• Muscle ATP 8 mM and phosphocreatine 30 mM agree with mammalian fibre data and human calibrated 31P-MRS values (ATP about 8.2 mM, PCr about 33 mM). The model's Pi 3 mM lies between fibre-type-dependent reports (about 0.8–6 mM) [11][23].
• The erythrocyte G6PD/6PGD, glutathione, and 2,3-BPG modules use substrate-scale constants and pool sizes in the range of published human erythrocyte models and experiments [24][25][26]. Their simplified one-step laws are still not equivalent to the detailed pH-, Mg²⁺-, haemoglobin-binding-, and oxygen-state- dependent rate equations in those publications.

Direct mismatches and deliberate departures

• PhosphateCarrier is written as two H⁺ per phosphate in both muscle and liver. The canonical mitochondrial phosphate carrier is normally represented as electroneutral Pi/H⁺ symport (one proton per phosphate). These are the two reaction-instance Does not match literature conclusions. Fluxion's value is retained because the source documents it as a deliberate reduced-model pH calibration.
• Thiolase uses a first-pass apparent Keq of 0.02 for the condensation 2 acetyl-CoA → acetoacetyl-CoA + CoA. The measured equilibrium favours thiolysis far more strongly (synthesis Keq ~1e-5), but at that value the acetoacetyl-CoA pass-through pool would sit at sub-nanomolar levels and the near-equilibrium reverse velocity would be ~1000× the forward, which the reduced model cannot resolve. Because acetoacetyl-CoA is a pulled intermediate whose exact level is not load-bearing (HMG-CoA synthase sets the chain flux), the value is raised to keep the pool representable (~0.5 µM) and the solver well-conditioned while preserving the unfavourable direction and the acetyl-CoA² drive. A declared model calibration, not the measured constant.
• CitrateMalateCarrier (the mitochondrial tricarboxylate carrier, SLC25A1) carries an NADPH_c product inhibitor with no real counterpart -- the carrier itself is not NADPH-regulated in vivo. It is a labeled modeling device standing in for a genuine calibration conflict: this carrier trades against MAL_c, the same tiny cytosolic malate pool the malate-aspartate shuttle maintains, so a constant Vf fast enough to sustain the cytosolic NADPH backup (ME1/IDH1) through a prolonged oxidant challenge disturbs that shuttle pool at rest well past the model's resting-stationarity tolerance, while a constant Vf slow enough to leave the shuttle undisturbed cannot sustain the backup. Gating it on the SAME NADPH signal that already throttles the two dehydrogenases it feeds (product inhibition, Ki 0.001) resolves this without inventing an unrelated fourth regulatory axis: the standing citrate/isocitrate pool alone buffers a brief demand, and this gate lets the carrier itself speed up only once that demand is sustained. A declared model calibration device, not a real mechanism of SLC25A1.
• The liver's G6PDehydrogenase/PhosphogluconateDehydrogenase run at Vf 0.01, calibration-capped near muscle's own low-capacity copy (0.008) rather than the literature "major NADPH producer" scale a real liver runs. Neither enzyme touches the malate-aspartate shuttle directly, but drawing G6P_c shifts cytosolic glycolytic flux (GAPDH's NAD+/NADH turnover) enough to ripple into ASP_c/ASP_m/ AKG_m/MAL_c -- measurably, and roughly linearly in Vf (0.94% resting disturbance at a naive Vf 0.05, 0.41% at 0.01), past the 0.5% rest-disturbance bar the shuttle's own fragility already demands elsewhere (CitrateMalateCarrier above). A declared calibration limit, not a measured rate; see OPEN-WORK.md 4.2.
• NADPHConsumption_liver carries an INS_b activator with no direct literature rate -- it is a labeled modeling device standing in for the liver's unmodeled lipogenesis/cholesterol synthesis (the real NADPH consumer a real liver's PPP feeds), gated on insulin because that biosynthetic program genuinely is insulin-driven (SREBP-1c) in vivo. A declared calibration device, not a mismeasured constant.
• AlanineTransaminase is written as the single step alanine → pyruvate, not the real alanine + alpha-ketoglutarate ⇌ pyruvate + glutamate transamination. The model tracks no whole-body nitrogen budget (no ammonia, no urea cycle, no free amino-acid pool beyond this one boundary species), so the amino group this reaction moves is not represented at all rather than wired through the malate-aspartate shuttle's AKG_c/GLU_c pair, which would either slowly drain or flood that near-equilibrium pair for no teaching benefit. Alanine and pyruvate are both 3-carbon, so the written step is exactly carbon-conserving on its own. A declared model simplification, not a mismeasured constant.

Composite beta-oxidation, ROS formation, peroxide removal, hormone secretion/clearance, gas exchange, systemic disposal, and proton-homeostat reactions are marked Not directly comparable or No reliable literature value found, not as mismatches. They represent several enzymes, transporters, tissues, or feedback loops with a single reduced-order term, so comparison to one purified-enzyme constant would be invalid. (Ketogenesis is now resolved into its three explicit enzymes -- thiolase, HMG-CoA synthase, HMG-CoA lyase -- and the non-oxidative pentose-phosphate branch is resolved into its isomerase, epimerase, transketolase, and transaldolase steps. These appear individually in the register below rather than as composite terms.)

Literature-search limitations

Consensus was used for broad discovery and primary-paper identification [20]-[26]. The installed Elicit connector could not run because the connected account does not include API access. BRENDA, SABIO-RK, eQuilibrator, Rhea, PubMed/PMC, and primary papers were used instead. Some older kinetic measurements are paywalled or expose numerical tables only in PDFs; where assay conditions or isoform identity could not be verified, the result is Insufficient context rather than a forced match. No literature evidence was inferred from search-result snippets alone.

Exhaustive model-value register

This compact register enumerates every value in the assembled default model. Identical tissue copies are shown together only when their complete displayed bundles agree; the reaction-instance counts above remain ungrouped. Concentration-like kinetic values are in mM unless the named state is an insulin/glucagon signal (pM) or Dpsi (mV). Vf and Vr are mM s⁻¹ in the reaction's home-compartment frame. Stoichiometric coefficients and charge are per model reaction event. Keq is the model's numerical chemical equilibrium constant and can be concentration-dimensional when the written reaction changes molecularity.

Reaction and kinetic-parameter register

• GlucoseSupply: stoichiometry ∅ → GLC_b — Not directly comparable; Vf 0.000564631 — No reliable literature value found (re-expressed ×1.265 from 0.05 for the full-mass tissues to 0.06324, re-anchored ×0.927 after the liver's per-kg recalibration to 0.058614, then ×0.366 after the muscle's, which also moved the brain's ~0.4 mmol/min into BrainGlucoseUptake, then ×0.055 when the liver's switches were re-anchored to the post-absorptive rest and the liver took over the resting supply, then ×1.04 after the red-cell stage, then ×1.0007 when muscle began burning fat (OPEN-WORK 2.1a), re-anchored to blood glucose's new ~4.62 mM set point — muscle takes up ~0.07 mmol/min less glucose, more than this whole term, so the liver releases a little less by its own hormonal control; then ×0.4584 to 0.000564631 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): the liver takes up the measured lactate and makes more of its glucose from it (hepatic output ~0.61 → ~0.64 mmol/min), so the kidney-sized remainder this stands in for shrinks by more than half); declared Vr 0 — No reliable literature value found; Keq 5 — No reliable literature value found; Haldane-derived Vr used 0.000564631 — Not directly comparable; Km {GLC_b 5} — No reliable literature value found; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PhosphateSupply (@muscle, @liver): stoichiometry ∅ → Pi_c — Not directly comparable; Vf 0.1 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Keq 4 — No reliable literature value found; Haldane-derived Vr used 0.0025 — Not directly comparable; Km {Pi_c 0.1} — No reliable literature value found; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BrainGlucoseUptake: stoichiometry GLC_b → ∅ — Not directly comparable (an artificial stand-in for the unmodeled brain's glucose use, to be retired with a brain tissue); Vf 0.000582 — No reliable literature value found (sized to the brain's measured ~0.4 mmol/min [52][53] at resting blood glucose); declared Vr 0 — No reliable literature value found; Km {GLC_b 1} — No reliable literature value found (first-pass); configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• ATPConsumption (@muscle): stoichiometry ATP_c + H2O_c → ADP_c + Pi_c + H_c + 0.05 Ca_c — Not directly comparable; Vf 0.012 — Matches literature (per liter of cytosol; ~0.0082 mM/s per liter of cell water at rest against the measured resting ATP turnover of 0.008 ± 0.002 mM/s [33]; was 0.026, ~3× that); declared Vr 0 — No reliable literature value found; Km {ATP_c 0.2, H2O_c 1, ADP_c 0.2, Pi_c 0.2, H_c 0.0001} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ATPConsumption (@liver): stoichiometry ATP_c + H2O_c → ADP_c + Pi_c + H_c + 0.023 Ca_c — Not directly comparable (the Ca²⁺ term is a lumped resting hepatocyte calcium source, calibrated to the measured ~0.22 µM [36]); Vf 0.27 — Matches literature (the liver's measured resting energy use, ~200 kcal/kg/day [32], at a P/O of ~2.5); declared Vr 0 — No reliable literature value found; Km {ATP_c 0.2, H2O_c 1, ADP_c 0.2, Pi_c 0.2, H_c 0.0001} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AMPRecovery_c (@muscle, @liver, @rbc): stoichiometry AMP_c + Pi_c + (−1) H_c → ADP_c — Not directly comparable (the proton integer is set by the reference forms (OPEN-WORK 5.1): AMP²⁻ + Pi²⁻ + H⁺ → ADP³⁻ + H₂O takes up a proton); Vf 0.01 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {AMP_c 0.05, Pi_c 0.3, ADP_c 0.1} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AMPRecovery_m (@muscle, @liver): stoichiometry AMP_m + Pi_m + (−1) H_m → ADP_m — Not directly comparable (the proton integer is set by the reference forms (OPEN-WORK 5.1): as the cytosolic copy); Vf 0.01 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {AMP_m 0.05, Pi_m 0.3, ADP_m 0.1} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• NADHConsumption (@muscle, @liver): stoichiometry NADH_c + H_c → NAD_c — Not directly comparable; Vf 0 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {NADH_c 0.05, NAD_c 0.05} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• FADH2Consumption (@muscle, @liver): stoichiometry FADH2_m → FAD_m — Not directly comparable; Vf 0 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {FADH2_m 0.05, FAD_m 0.05} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ProtonBuffer_b: stoichiometry BufferH_b → Buffer_b + H_b — Matches literature; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 7.94328e-05 — Insufficient context; Haldane-derived Vr used 6.2946271 — Not directly comparable; Km {BufferH_b 1, Buffer_b 1, H_b 0.0001} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BloodAcidBaseRegulation: stoichiometry ∅ → H_b — Not directly comparable; Vf 0.00723926 — No reliable literature value found (re-expressed ×0.235 to 0.00094111 for the full-mass tissues; reshaped from a self-inhibited source to a two-way homeostat and re-anchored to 0.020118 after the liver's per-kg recalibration, then ×0.504 after the muscle's, whose resting lactate-and-proton export stopped, then ×2.23 when the post-absorptive liver began mobilising glycogen at rest and phosphorylase's tracked phosphate proton made the body a larger acid producer, ×0.965 after the red-cell stage, then ×0.326 when muscle began burning fat (OPEN-WORK 2.1a): the body's resting net acid production fell with the muscle's shift to fat; unchanged at 0.00711243 when the proton integers were corrected (OPEN-WORK 5.4), which removed the standing acid load, so the term now idles at rest; then ×1.0178 to 0.00723926 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; Keq 4.445e-05 — No reliable literature value found (the set point of the regulation, not a chemical equilibrium: moved from the pH-7.40 proton concentration 3.98e-05 to 4.396e-05 when the standing acid load it had been absorbing was removed at its source (OPEN-WORK 5.4), then to 4.445e-05 when the ketone disposals, NADPH sinks and AMP recoveries began consuming a proton (OPEN-WORK 5.1), so the pool still rests at pH 7.356; setting it to 3.98e-05 would rest blood at 7.40 and the cytosols at 7.00); Haldane-derived Vr used 0.00723926 — Not directly comparable; Km {H_b 4.445e-05} — No reliable literature value found; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• CreatineKinase_c (@muscle): stoichiometry PCr_c + ADP_c + H_c → Cr_c + ATP_c — Matches literature; Vf 50 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1.5e+06 — Matches literature; Haldane-derived Vr used 39.68254 — Not directly comparable; Km {PCr_c 0.72, ADP_c 0.035, H_c 0.0001, Cr_c 6, ATP_c 0.5} — Matches literature; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycogenPhosphorylase (@muscle): stoichiometry GLY_c + Pi_c → G1P_c — Matches literature; Vf 0.01 — Not directly comparable (the resting, phosphorylase-kinase-off activity; was 0.35, which ran a resting futile cycle with the synthase); declared Vr 0 — Not directly comparable; Km {GLY_c 2, Pi_c 5, G1P_c 0.05} — Insufficient context; inhibitors {ATP_c: Ki 4, Hill n 2, G6P_c: Ki 0.5, Hill n 2} — Insufficient context; activators {AMP_c: Ka 0.05, Hill n 2, maximum fold 15, Ca_c: Ka 0.0002, Hill n 2, maximum fold 10 — phosphorylase kinase's Ca²⁺/calmodulin activation [44], first-pass constants} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PhosphoglucoMutase (@muscle, @liver): stoichiometry G1P_c → G6P_c — Matches literature; Vf 8 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 17 — Matches literature; Haldane-derived Vr used 0.94117647 — Not directly comparable; Km {G1P_c 0.05, G6P_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• UGPase (@muscle): stoichiometry G1P_c + UTP_c → UDPGlc_c + 2 Pi_c — Matches literature; Vf 4 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {G1P_c 0.1, UTP_c 0.1} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycogenSynthase (@muscle): stoichiometry UDPGlc_c → GLY_c + UDP_c + H_c — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): UDP-glucose²⁻ → glycogen + UDP³⁻ + H⁺); Vf 0.001375 — Not directly comparable (calibrated well below a naive reuse of the former lumped step's Vf -- moving G6P_c from co-substrate to allosteric activator removed a self-limiting throttle the old stoichiometry had, so a naive Vf ran ~5-10x too fast at rest and drove cytosolic pH to ~8.6 within 90 minutes; see the deliberate-departures note. Cut a further ×0.2 from 0.0055 to match muscle's calcium-gated phosphorylase at rest: turnover ~20 µmol/kg/min; then ×1.25 when muscle began burning fat (OPEN-WORK 2.1a): at 0.0011 the store lost ~4.7 µmol glucosyl/kg/min at rest — inside the 0.3%/10 min gate only because the store is large — which left the muscle as lactate once fat slowed pyruvate oxidation; now stationary in flux terms); declared Vr 0 — Not directly comparable; Km {UDPGlc_c 0.2, GLY_c 50} — Insufficient context; inhibitors {AMP_c: Ki 0.05, Hill n 2} — Insufficient context; activators {G6P_c: Ka 0.5, Hill n 1.5, maximum fold 4} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• NucleosideDiphosphateKinase (@muscle): stoichiometry UDP_c + ATP_c → UTP_c + ADP_c — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Matches literature (NDK trades nucleotides of essentially equal phosphoanhydride bond energy); Haldane-derived Vr used 2 — Not directly comparable; Km {UDP_c 0.05, ATP_c 0.5, UTP_c 0.05, ADP_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Hexokinase (@muscle): stoichiometry GLC_c + ATP_c → G6P_c + ADP_c + H_c — Matches literature; Vf 0.38 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {GLC_c 0.05, ATP_c 0.5, G6P_c 0.05, ADP_c 0.5} — Insufficient context; inhibitors {G6P_c: Ki 0.05, Hill n 1.2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PGI (@muscle, @liver): stoichiometry G6P_c → F6P_c — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.35087719 — Matches literature; Haldane-derived Vr used 5.7 — Not directly comparable; Km {G6P_c 0.1, F6P_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• PGI (@rbc): stoichiometry G6P_c → F6P_c — Matches literature; Vf 0.4805 — Matches literature (the measured red-cell activity, 60.8 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 0.35087719 — Matches literature; Haldane-derived Vr used 1.369 — Not directly comparable; Km {G6P_c 0.1, F6P_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PFK1 (@muscle): stoichiometry F6P_c + ATP_c → F16BP_c + ADP_c + H_c — Matches literature; Vf 0.68 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {F6P_c 0.1, ATP_c 0.3} — Insufficient context; inhibitors {ATP_c: Ki 2, Hill n 2, H_c: Ki 0.0001, Hill n 2.5} — Insufficient context; activators {AMP_c: Ka 0.1, Hill n 2, maximum fold 10, F26BP_c: Ka 0.015, Hill n 2, maximum fold 4} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Aldolase (@muscle, @liver): stoichiometry F16BP_c → DHAP_c + GAP_c — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.08 — Matches literature; Haldane-derived Vr used 5 — Not directly comparable; Km {F16BP_c 0.05, DHAP_c 0.1, GAP_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• Aldolase (@rbc): stoichiometry F16BP_c → DHAP_c + GAP_c — Matches literature; Vf 0.02521 — Matches literature (the measured red-cell activity, 3.19 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 0.08 — Matches literature; Haldane-derived Vr used 0.06303 — Not directly comparable; Km {F16BP_c 0.05, DHAP_c 0.1, GAP_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• TPI (@muscle, @liver): stoichiometry DHAP_c → GAP_c — Matches literature; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.045454545 — Matches literature; Haldane-derived Vr used 110 — Not directly comparable; Km {DHAP_c 0.05, GAP_c 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• TPI (@rbc): stoichiometry DHAP_c → GAP_c — Matches literature; Vf 16.68 — Matches literature (the measured red-cell activity, 2111 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 0.045454545 — Matches literature; Haldane-derived Vr used 367 — Not directly comparable; Km {DHAP_c 0.05, GAP_c 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GAPDH (@muscle, @liver): stoichiometry GAP_c + Pi_c + NAD_c → BPG13_c + NADH_c + H_c — Matches literature; Vf 3.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 8e-05 — Matches literature (0.08 M⁻¹, ΔG°′ ≈ +6.3 kJ/mol at pH 7 [3], in mM⁻¹; it was entered as 0.08 in mM⁻¹, 1000× too favourable -- corrected in the red-cell stage); Haldane-derived Vr used 9.115e+04 — Not directly comparable; Km {GAP_c 0.05, Pi_c 0.3, NAD_c 0.08, BPG13_c 0.05, NADH_c 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• GAPDH (@rbc): stoichiometry GAP_c + Pi_c + NAD_c → BPG13_c + NADH_c + H_c — Matches literature; Vf 1.786 — Matches literature (the measured red-cell activity, 226 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 8e-05 — Matches literature (0.08 M⁻¹, ΔG°′ ≈ +6.3 kJ/mol at pH 7 [3], in mM⁻¹; it was entered as 0.08 in mM⁻¹, 1000× too favourable -- corrected in the red-cell stage); Haldane-derived Vr used 4.651e+04 — Not directly comparable; Km {GAP_c 0.05, Pi_c 0.3, NAD_c 0.08, BPG13_c 0.05, NADH_c 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PGK (@muscle, @liver): stoichiometry BPG13_c + ADP_c → PG3_c + ATP_c — Matches literature; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 3300 — Matches literature; Haldane-derived Vr used 0.02020202 — Not directly comparable; Km {BPG13_c 0.05, ADP_c 0.15, PG3_c 0.2, ATP_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• PGK (@rbc): stoichiometry BPG13_c + ADP_c → PG3_c + ATP_c — Matches literature; Vf 2.529 — Matches literature (the measured red-cell activity, 320 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 3300 — Matches literature; Haldane-derived Vr used 0.01022 — Not directly comparable; Km {BPG13_c 0.05, ADP_c 0.15, PG3_c 0.2, ATP_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PGM (@muscle, @liver): stoichiometry PG3_c → PG2_c — Matches literature; Vf 4 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.1 — Matches literature (the measured [2-PG]/[3-PG], 0.087–0.116 [93][94]; was 0.17, the textbook +4.4 kJ/mol); Haldane-derived Vr used 40 — Not directly comparable; Km {PG3_c 0.1, PG2_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• PGM (@rbc): stoichiometry PG3_c → PG2_c — Matches literature; Vf 0.298 — Matches literature (the measured red-cell activity, 37.71 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 0.1 — Matches literature (the measured [2-PG]/[3-PG], 0.087–0.116 [93][94]; was 0.17, the textbook +4.4 kJ/mol); Haldane-derived Vr used 2.98 — Not directly comparable; Km {PG3_c 0.1, PG2_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Enolase (@muscle, @liver): stoichiometry PG2_c → PEP_c + H2O_c — Matches literature; Vf 2.8 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 4.7 — Matches literature (from the measured ΔG°′ −2.8 kJ/mol at 25 °C and ΔH°′ +27 kJ/mol [92], extrapolated to 37 °C; was 0.5, the textbook +1.8 kJ/mol); Haldane-derived Vr used 0.595745 — Not directly comparable; Km {PG2_c 0.1, PEP_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• Enolase (@rbc): stoichiometry PG2_c → PEP_c + H2O_c — Matches literature; Vf 0.0426 — Matches literature (the measured red-cell activity, 5.39 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 4.7 — Matches literature (from the measured ΔG°′ −2.8 kJ/mol at 25 °C and ΔH°′ +27 kJ/mol [92], extrapolated to 37 °C; was 0.5, the textbook +1.8 kJ/mol); Haldane-derived Vr used 0.009064 — Not directly comparable; Km {PG2_c 0.1, PEP_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateKinase (@muscle): stoichiometry PEP_c + ADP_c + H_c → PYR_c + ATP_c — Matches literature; Vf 4.4 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {PEP_c 0.08, ADP_c 0.15, H_c 0.0001} — Insufficient context; inhibitors {ATP_c: Ki 2, Hill n 2} — Insufficient context; activators {F16BP_c: Ka 0.05, Hill n 2, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• PyruvateKinase (@rbc): stoichiometry PEP_c + ADP_c + H_c → PYR_c + ATP_c — Matches literature; Vf 0.1185 — Matches literature (the measured red-cell activity, 15 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Km {PEP_c 0.25, ADP_c 0.3, H_c 0.0001} — Insufficient context (the erythroid PK-R binds PEP and ADP more weakly than muscle's enzyme; first-pass within its S0.5 ~0.2–0.5 mM and ADP Km ~0.3); inhibitors {ATP_c: Ki 2, Hill n 2} — Insufficient context; activators {F16BP_c: Ka 0.05, Hill n 2, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• LactateDehydrogenase_c (@muscle, @liver): stoichiometry PYR_c + NADH_c + H_c → LAC_c + NAD_c — Matches literature; Vf 6 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 9.009e+07 — Matches literature (Williamson et al., K = 1.11e-11 M at 38 °C and ionic strength 0.25 [8]; was 3.6e+08, 4× high for body temperature); Haldane-derived Vr used 0.333000 — Not directly comparable; Km {PYR_c 0.1, NADH_c 0.03, H_c 0.0001, LAC_c 10, NAD_c 0.15} — Insufficient context; inhibitors {LAC_c: Ki 20, Hill n 1.2} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• LactateDehydrogenase_c (@rbc): stoichiometry PYR_c + NADH_c + H_c → LAC_c + NAD_c — Matches literature; Vf 1.581 — Matches literature (the measured red-cell activity, 200 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 9.009e+07 — Matches literature (Williamson et al., K = 1.11e-11 M at 38 °C and ionic strength 0.25 [8]; was 3.6e+08, 4× high for body temperature); Haldane-derived Vr used 0.087746 — Not directly comparable; Km {PYR_c 0.1, NADH_c 0.03, H_c 0.0001, LAC_c 10, NAD_c 0.15} — Insufficient context; inhibitors {LAC_c: Ki 20, Hill n 1.2} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• LactateTransport_c_to_b (@muscle, @rbc): stoichiometry LAC_c + H_c → LAC_b + H_b — Not directly comparable; Vf 0.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.5 — Insufficient context; Haldane-derived Vr used 0.2 — Not directly comparable; Km {LAC_c 1, LAC_b 1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BloodLactateConsumption: stoichiometry LAC_b + H_b → ∅ — Not directly comparable; Vf 0.04 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {LAC_b 1, H_b 1e-06, O2_b 0.003} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BloodLactateProduction: stoichiometry ∅ → LAC_b + H_b — Not directly comparable; Vf 0.038833 — No reliable literature value found (re-expressed ×0.950 from 0.035 for the full-mass tissues to 0.03325, then re-anchored ×1.143 after the muscle's per-kg recalibration stopped its resting lactate export, ×1.0065 after the red-cell stage and ×1.0018 when muscle began burning fat (OPEN-WORK 2.1a); then ×1.0136 to 0.038833 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; inhibitors {LAC_b: Ki 1, Hill n 2} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• MalateDehydrogenase_c (@muscle, @liver): stoichiometry MAL_c + NAD_c → OAA_c + NADH_c + H_c — Matches literature; Vf 0.25 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.6e-05 — Matches literature; Haldane-derived Vr used 4807.6923 — Not directly comparable; Km {MAL_c 0.08, NAD_c 0.1, OAA_c 0.05, NADH_c 0.08} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AspartateAminotransferase_c (@muscle, @liver): stoichiometry ASP_c + AKG_c → OAA_c + GLU_c — Matches literature; Vf 0.25 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.147 — Matches literature; Haldane-derived Vr used 2.8344671 — Not directly comparable; Km {ASP_c 0.9, AKG_c 0.1, OAA_c 0.05, GLU_c 3} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AspartateAminotransferase_m (@muscle, @liver): stoichiometry ASP_m + AKG_m → OAA_m + GLU_m — Matches literature; Vf 2.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.147 — Matches literature; Haldane-derived Vr used 28.344671 — Not directly comparable; Km {ASP_m 0.9, AKG_m 0.1, OAA_m 0.05, GLU_m 3} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OxoglutarateMalateCarrier (@muscle, @liver): stoichiometry MAL_c + AKG_m → MAL_m + AKG_c — Not directly comparable; Vf 0.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.5 — Not directly comparable; Km {MAL_c 0.4, AKG_m 0.1, MAL_m 0.4, AKG_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• AspartateGlutamateCarrier (@muscle, @liver): stoichiometry ASP_m + GLU_c + H_i + 148.14815 Dpsi_m → ASP_c + GLU_m + H_m — Not directly comparable; Vf 0.25 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.25 — Not directly comparable; Km {ASP_m 0.05, GLU_c 2.8, ASP_c 0.05, GLU_m 2.8} — Insufficient context; configuration {reversible yes, charge -1, home m, phosphate-proton tracking no} — Not directly comparable.
• G3PDH_cyt (@muscle, @liver): stoichiometry DHAP_c + NADH_c + H_c → G3P_c + NAD_c — Matches literature; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 10000 — Matches literature; Haldane-derived Vr used 0.041666667 — Not directly comparable; Km {DHAP_c 0.1, NADH_c 0.03, G3P_c 0.5, NAD_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• G3PDH_mito (@muscle): stoichiometry G3P_c + FAD_m → DHAP_c + FADH2_m — Matches literature; Vf 0.0125 — Not directly comparable (cut ×0.01 from 10 in the muscle stage, ×0.5 again in the red-cell stage once GAPDH's equilibrium constant was corrected, and ×0.25 (0.05 → 0.0125) with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3) so muscle pyruvate stays in range (~99 µM; G3P rises to ~0.61 mM against the measured ~0.25 [51]); originally calibrated to the measured resting muscle G3P [51]; see the NADH-shuttles section); declared Vr 0 — Not directly comparable; Keq 1.4e+07 — Matches literature (from the ~0.22 V two-electron drop from the DHAP/G3P couple, E°′ ≈ −0.19 V, to the ubiquinone-level flavin, ≈ +0.03 V [5]; was 2); Haldane-derived Vr used 1.785e-10 — Not directly comparable; Km {G3P_c 0.5, FAD_m 0.05, DHAP_c 0.1, FADH2_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.

• G3PDH_mito (@liver): stoichiometry G3P_c + FAD_m → DHAP_c + FADH2_m — Matches literature; Vf 0.09 — Not directly comparable (×0.6 of muscle's per mitochondrion since the red-cell stage — liver is the lowest-mGPDH tissue [55] — then ×3 (0.03 → 0.09) with the measured LDH constant (OPEN-WORK 4.3): the liver now takes up ~170 µmol/kg/min of lactate and its NADH load had dropped cytosolic NAD⁺/NADH to ~190; this puts it above muscle's capacity per liter of matrix, as a stand-in for the under-sized malate–aspartate shuttle; calibrated to the measured hepatic cytosolic NAD⁺/NADH [8]; see the NADH-shuttles section); declared Vr 0 — Not directly comparable; Keq 1.4e+07 — Matches literature (from the ~0.22 V two-electron drop from the DHAP/G3P couple, E°′ ≈ −0.19 V, to the ubiquinone-level flavin, ≈ +0.03 V [5]; was 2); Haldane-derived Vr used 1.287e-09 — Not directly comparable; Km {G3P_c 0.5, FAD_m 0.05, DHAP_c 0.1, FADH2_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• OM_Pyruvate (@muscle): stoichiometry PYR_c → PYR_i — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {PYR_c 0.1, PYR_i 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_Pyruvate (@liver): stoichiometry PYR_c → PYR_i — Not directly comparable; Vf 30 — Not directly comparable (×3, the liver's 3× mitochondrial outer membrane); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {PYR_c 0.1, PYR_i 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_Pi (@muscle): stoichiometry Pi_c → Pi_i — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {Pi_c 0.18, Pi_i 0.18} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_Pi (@liver): stoichiometry Pi_c → Pi_i — Not directly comparable; Vf 30 — Not directly comparable (×3, the liver's 3× mitochondrial outer membrane); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {Pi_c 0.18, Pi_i 0.18} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_ADP (@muscle): stoichiometry ADP_c → ADP_i — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {ADP_c 0.06, ADP_i 0.06} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_ADP (@liver): stoichiometry ADP_c → ADP_i — Not directly comparable; Vf 30 — Not directly comparable (×3, the liver's 3× mitochondrial outer membrane); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {ADP_c 0.06, ADP_i 0.06} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_ATP (@muscle): stoichiometry ATP_c → ATP_i — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {ATP_c 0.06, ATP_i 0.06} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_ATP (@liver): stoichiometry ATP_c → ATP_i — Not directly comparable; Vf 30 — Not directly comparable (×3, the liver's 3× mitochondrial outer membrane); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {ATP_c 0.06, ATP_i 0.06} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_H (@muscle): stoichiometry H_c → H_i — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {H_c 0.0001, H_i 0.0001} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OM_H (@liver): stoichiometry H_c → H_i — Not directly comparable; Vf 30 — Not directly comparable (×3, the liver's 3× mitochondrial outer membrane); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {H_c 0.0001, H_i 0.0001} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• MatrixProtonHomeostat (@muscle, @liver): stoichiometry H_i → H_m — Not directly comparable; Vf 50 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Keq 0.39810717 — No reliable literature value found; Haldane-derived Vr used 125.59432 — Not directly comparable; Km {H_i 0.0001, H_m 0.0001} — No reliable literature value found; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• PlasmaProtonHomeostat (@muscle, @liver, @rbc): stoichiometry H_c → H_b — Not directly comparable; Vf 0.5 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Keq 0.39810717 — No reliable literature value found; Haldane-derived Vr used 1.2559432 — Not directly comparable; Km {H_c 0.0001, H_b 0.0001} — No reliable literature value found; configuration {reversible yes, charge 0, home c, phosphate-proton tracking no} — Not directly comparable.
• PyruvateCarrier (@muscle, @liver): stoichiometry PYR_i + H_i → PYR_m + H_m — Matches literature; Vf 7.2 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 7.2 — Not directly comparable; Km {PYR_i 0.1, PYR_m 0.1} — Insufficient context; inhibitors {PYR_m: Ki 2, Hill n 1.5} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• PhosphateCarrier (@muscle, @liver): stoichiometry Pi_i + 2 H_i → Pi_m + 2 H_m — Does not match literature; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {Pi_i 0.2, Pi_m 0.2} — Insufficient context; inhibitors {Pi_m: Ki 4, Hill n 2} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• AdenineNucleotideTranslocase (@muscle): stoichiometry ATP_m + ADP_i + 148.14815 Dpsi_m → ATP_i + ADP_m — Not directly comparable; Vf 1.1 — Not directly comparable (base capacity ×0.1, restored up to 10× by the ADP activator in work); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 1.1 — Not directly comparable; Km {ATP_m 0.1, ADP_i 0.01, ATP_i 0.1, ADP_m 0.01} — Insufficient context; inhibitors {ATP_i: Ki 6, Hill n 2} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2, ADP_i: Ka 0.03, Hill n 2.2, maximum fold 10 — the in-vivo second-order ADP control of oxidative phosphorylation [46]} — Matches literature; configuration {reversible yes, charge -1, home m, phosphate-proton tracking no} — Not directly comparable.

• AdenineNucleotideTranslocase (@liver): stoichiometry ATP_m + ADP_i + 148.14815 Dpsi_m → ATP_i + ADP_m — Not directly comparable; Vf 11 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 11 — Not directly comparable; Km {ATP_m 0.1, ADP_i 0.01, ATP_i 0.1, ADP_m 0.01} — Insufficient context; inhibitors {ATP_i: Ki 6, Hill n 2} — Insufficient context; activators {ADP_i: Ka 0.08, Hill n 1.6, maximum fold 2, Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible yes, charge -1, home m, phosphate-proton tracking no} — Not directly comparable.
• AdenylateKinase_c (@muscle, @liver): stoichiometry ATP_c + AMP_c → 2 ADP_c — Matches literature; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.2727273 — Matches literature; Haldane-derived Vr used 4.4 — Not directly comparable; Km {ATP_c 0.1, AMP_c 0.05, ADP_c 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AdenylateKinase_m (@muscle, @liver): stoichiometry ATP_m + AMP_m → 2 ADP_m — Matches literature; Vf 50 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.2727273 — Matches literature; Haldane-derived Vr used 44 — Not directly comparable; Km {ATP_m 0.1, AMP_m 0.05, ADP_m 0.1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• CalciumUniporter (@muscle, @liver): stoichiometry Ca_c + 296.2963 Dpsi_m → Ca_m — Matches literature; Vf 0.03 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.15 — Not directly comparable; Km {Ca_c 0.001, Ca_m 0.005} — Insufficient context; configuration {reversible yes, charge -2, home m, phosphate-proton tracking no} — Not directly comparable.
• CalciumEffluxMito (@muscle, @liver): stoichiometry Ca_m → Ca_c — Matches literature; Vf 0.02 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {Ca_m 0.002} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• CalciumReuptake (@muscle, @liver): stoichiometry Ca_c → ∅ — Matches literature; Vf 0.03 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {Ca_c 0.001} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateDehydrogenase (@muscle): stoichiometry PYR_m + NAD_m + CoA_m → AcCoA_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- PYR⁻ + NAD⁻ + CoA⁴⁻ → AcCoA⁴⁻ + CO₂ + NADH²⁻ balances in charge and atoms as written (it carried one, which together with citrate synthase's missing one over-released 2 H⁺ per pyruvate oxidized); Alberty 2003); Vf 1.1 — Not directly comparable (×0.05 of the shared 22, to the measured total PDC activity of human vastus lateralis, ~3 mmol/min/kg wet [50]); declared Vr 0 — Not directly comparable; Km {PYR_m 0.08, NAD_m 0.1, CoA_m 0.007} — Insufficient context (CoA 7 µM from rat-heart PDC [47]); inhibitors {NADH_m: Ki 0.02, Hill n 2, AcCoA_m: Ki 0.013, Hill n 1, competitive with CoA_m [47]} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateDehydrogenase (@liver): stoichiometry PYR_m + NAD_m + CoA_m → AcCoA_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- PYR⁻ + NAD⁻ + CoA⁴⁻ → AcCoA⁴⁻ + CO₂ + NADH²⁻ balances in charge and atoms as written (it carried one, which together with citrate synthase's missing one over-released 2 H⁺ per pyruvate oxidized); Alberty 2003); Vf 22 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {PYR_m 0.08, NAD_m 0.1, CoA_m 0.05} — Insufficient context; inhibitors {NADH_m: Ki 0.02, Hill n 2, AcCoA_m: Ki 0.6, Hill n 1.5, GCG_b: Ki 15.625, Hill n 3 (post-absorptive re-anchor, liver follow-up: was 25) — a lumped stand-in for fasting PDK4 inactivation of hepatic PDH [38]} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateCarboxylase (@muscle, @liver): stoichiometry PYR_m + CO2_m + ATP_m → OAA_m + ADP_m + Pi_m + 2 H_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): pyruvate⁻ + CO₂ + ATP⁴⁻ + H₂O → OAA²⁻ + ADP³⁻ + Pi²⁻ + 2 H⁺; Alberty 2003); Vf 0.0093 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {PYR_m 0.08, CO2_m 0.02, ATP_m 0.08, OAA_m 0.05, ADP_m 0.08, Pi_m 0.2} — Insufficient context; inhibitors {OAA_m: Ki 0.8, Hill n 2, MAL_m: Ki 0.5, Hill n 2, CIT_m: Ki 1, Hill n 2} — Insufficient context; activators {AcCoA_m: Ka 0.08, Hill n 1.8, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Cataplerosis (@muscle): stoichiometry CIT_m → ∅ — Matches literature; Vf 0.0004 — Not directly comparable (an artificial drain; cut ×0.02 from 0.02, which was sized for a carboxylase loop at 58% of citrate-synthase flux and would remove ~80% of the cycle's flux at a physiological matrix citrate); declared Vr 0 — Not directly comparable; Km {CIT_m 0.5} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• CitrateSynthase (@muscle): stoichiometry AcCoA_m + OAA_m → CIT_m + CoA_m + H_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): AcCoA⁴⁻ + OAA²⁻ + H₂O → citrate³⁻ + CoA⁴⁻ + H⁺ -- the thioester hydrolysis releases one proton; Alberty 2003); Vf 24 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {AcCoA_m 0.01, OAA_m 0.005, CoA_m 0.05} — Insufficient context; inhibitors {CIT_m: Ki 5, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Aconitase (@muscle, @liver): stoichiometry CIT_m → ICIT_m — Matches literature; Vf 20 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.066666667 — Matches literature; Haldane-derived Vr used 300 — Not directly comparable; Km {CIT_m 0.08, ICIT_m 0.08} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• IsocitrateDehydrogenase (@muscle): stoichiometry ICIT_m + NAD_m → AKG_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- isocitrate³⁻ + NAD⁻ → AKG²⁻ + CO₂ + NADH²⁻ balances as written; Alberty 2003); Vf 8.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {ICIT_m 1.27, NAD_m 0.1}, isocitrate Hill coefficient 1.5 — Matches literature (human IDH3 with citrate bound: S0.5 1.27 mM, Hill ~1.5 [54]; NAD_m 0.1 against the measured S0.5 0.14 mM [54]); inhibitors {ATP_m: Ki 1.8, Hill n 1, NADH_m: Ki 0.02, Hill n 1, both competitive with NAD_m (ATP I₀.₅ 1.8 mM, bovine heart enzyme [48][49])} — Insufficient context; activators {ADP_m: Ka 0.2, Hill n 2, maximum fold 2, Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• IsocitrateDehydrogenase (@liver): stoichiometry ICIT_m + NAD_m → AKG_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- isocitrate³⁻ + NAD⁻ → AKG²⁻ + CO₂ + NADH²⁻ balances as written; Alberty 2003); Vf 8.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {ICIT_m 0.06, NAD_m 0.1} — Insufficient context; inhibitors {ATP_m: Ki 1.5, Hill n 2, NADH_m: Ki 0.02, Hill n 2} — Insufficient context; activators {ADP_m: Ka 0.2, Hill n 2, maximum fold 2, Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AlphaKGDehydrogenase (@muscle): stoichiometry AKG_m + NAD_m + CoA_m → SucCoA_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- AKG²⁻ + NAD⁻ + CoA⁴⁻ → succinyl-CoA⁵⁻ + CO₂ + NADH²⁻ balances as written; Alberty 2003); Vf 6.8 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {AKG_m 0.07, NAD_m 0.1, CoA_m 0.05} — Insufficient context; inhibitors {NADH_m: Ki 0.02, Hill n 1, competitive with NAD_m, SucCoA_m: Ki 0.5, Hill n 1, competitive with CoA_m — the measured mechanism; the Ki values are the shared model's} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• AlphaKGDehydrogenase (@liver): stoichiometry AKG_m + NAD_m + CoA_m → SucCoA_m + CO2_m + NADH_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton -- AKG²⁻ + NAD⁻ + CoA⁴⁻ → succinyl-CoA⁵⁻ + CO₂ + NADH²⁻ balances as written; Alberty 2003); Vf 6.8 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {AKG_m 0.07, NAD_m 0.1, CoA_m 0.05} — Insufficient context; inhibitors {NADH_m: Ki 0.02, Hill n 2, SucCoA_m: Ki 0.5, Hill n 1.5} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• SuccinylCoASynthetase (@muscle, @liver): stoichiometry SucCoA_m + ADP_m + Pi_m → SUC_m + ATP_m + CoA_m — Matches literature; Vf 8.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 3.8 — Matches literature; Haldane-derived Vr used 0.59649123 — Not directly comparable; Km {SucCoA_m 0.06, ADP_m 0.1, Pi_m 0.5, SUC_m 0.08, ATP_m 0.2, CoA_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• SuccinateDehydrogenase (@muscle, @liver): stoichiometry SUC_m + FAD_m → FUM_m + FADH2_m — Matches literature; Vf 8 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Matches literature; Haldane-derived Vr used 8 — Not directly comparable; Km {SUC_m 0.08, FAD_m 0.05, FUM_m 0.08, FADH2_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Fumarase (@muscle, @liver): stoichiometry FUM_m + H2O_m → MAL_m — Matches literature; Vf 44 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 4.4 — Matches literature; Haldane-derived Vr used 10 — Not directly comparable; Km {FUM_m 0.08, H2O_m 1, MAL_m 0.08} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• MalateDehydrogenase (@muscle, @liver): stoichiometry MAL_m + NAD_m → OAA_m + NADH_m + H_m — Matches literature; Vf 7 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.6e-05 — Insufficient context; Haldane-derived Vr used 134615 — Not directly comparable; Km {MAL_m 0.08, NAD_m 0.1, OAA_m 0.05, NADH_m 0.08} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ComplexI (@muscle, @liver): stoichiometry NADH_m + CoQ_m + 5 H_m → NAD_m + CoQH2_m + 4 H_i + 592.59259 Dpsi_m — Matches literature; Vf 0.18 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 7.4e+11 — Matches literature; Haldane-derived Vr used 4.86486e-13 — Not directly comparable; Km {NADH_m 0.05, CoQ_m 0.05, NAD_m 0.1, CoQH2_m 0.05} — Insufficient context; configuration {reversible yes, charge 4, home inferred, phosphate-proton tracking no, electron-transfer steepness 1, cap 40} — Not directly comparable.
• ComplexII (@muscle, @liver): stoichiometry FADH2_m + CoQ_m → FAD_m + CoQH2_m — Matches literature; Vf 8.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.85 — Insufficient context; Haldane-derived Vr used 2.9824561 — Not directly comparable; Km {FADH2_m 0.05, CoQ_m 0.05, FAD_m 0.05, CoQH2_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ComplexIII (@muscle, @liver): stoichiometry CoQH2_m + 2 CytC_ox_i + 2 H_m → CoQ_m + 2 CytC_red_i + 4 H_i + 296.2963 Dpsi_m — Matches literature; Vf 0.18 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 6.3e+06 — Matches literature; Haldane-derived Vr used 2.85714e-08 — Not directly comparable; Km {CoQH2_m 0.05, CytC_ox_i 0.05, CoQ_m 0.05, CytC_red_i 0.05} — Insufficient context; configuration {reversible yes, charge 2, home m, phosphate-proton tracking no, electron-transfer steepness 1, cap 40} — Not directly comparable.
• ComplexIV (@muscle, @liver): stoichiometry 2 CytC_red_i + 0.5 O2_m + 4 H_m → 2 CytC_ox_i + H2O_m + 2 H_i + 592.59259 Dpsi_m — Matches literature; Vf 0.18 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1.9e+18 — Matches literature; Haldane-derived Vr used 9.47368e-17 — Not directly comparable; Km {CytC_red_i 0.05, O2_m 0.001, CytC_ox_i 0.05} — Insufficient context; configuration {reversible yes, charge 4, home m, phosphate-proton tracking no, electron-transfer steepness 1, cap 40} — Not directly comparable.
• ATPSynthase (@muscle, @liver): stoichiometry ADP_m + Pi_m + 2.6666667 H_i + 395.06173 Dpsi_m → ATP_m + H2O_m + 1.6666667 H_m — Matches literature; Vf 13.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 7.3e-06 — Matches literature; Haldane-derived Vr used 4.62329e+06 — Not directly comparable; Km {ADP_m 0.05, Pi_m 0.8, ATP_m 0.1} — Insufficient context; activators {Ca_m: Ka 0.001, Hill n 2, maximum fold 2} — Matches literature; configuration {reversible yes, charge -2.6666667, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ProtonLeak (@muscle, @liver): stoichiometry H_i + 148.14815 Dpsi_m → H_m — Matches literature; Vf 0.011 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {H_i 0.0001} — Insufficient context; activators {Dpsi_m: Ka 175, Hill n 4, maximum fold 25} — Insufficient context; configuration {reversible no, charge -1, home m, phosphate-proton tracking no} — Not directly comparable.
• ROS_Generation_Q (@muscle, @liver): stoichiometry 2 O2_m + CoQH2_m → 2 O2super_m + CoQ_m + 2 H_m — Matches literature; Vf 0.004 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {O2_m 0.02, CoQH2_m 0.05, O2super_m 0.01, CoQ_m 0.05} — Insufficient context; activators {CoQH2_m: Ka 0.15, Hill n 2, maximum fold 2, Dpsi_m: Ka 180, Hill n 2, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• SOD_m (@muscle, @liver): stoichiometry 2 O2super_m + 2 H_m → H2O2_m + O2_m — Matches literature; Vf 2.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {O2super_m 0.01, H2O2_m 0.01, O2_m 0.02} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PeroxideDetox_m (@muscle, @liver): stoichiometry 2 H2O2_m → 2 H2O_m + O2_m — Matches literature; Vf 1.8 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {H2O2_m 0.01, H2O_m 1, O2_m 0.02} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OxygenSupply: stoichiometry ∅ → O2_b — Not directly comparable; Vf 0.13737 — No reliable literature value found (re-anchored ×1.035 when muscle began burning fat (OPEN-WORK 2.1a) — fat needs ~15% more O₂ per ATP than glucose; the ceiling: 25× the resting supply, sized from VO₂max less the unmodeled tissues' share — see the narrative; before that re-expressed ×1.187 from 0.02 for the full-mass tissues, re-anchored ×1.242 to 0.029493 when the liver's O₂ use was brought to its literature rate, then ×0.567 when the muscle's was, ×0.981 after the liver follow-up and ×1.0044 at the red-cell stage, to 0.0164864; then ×1.0122 to 0.13737 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; Km {O2_b 0.1} — No reliable literature value found; inhibitors {O2_b: Ki 0.05172, Hill n 6 — Ki solved so the resting supply is unchanged} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OxygenUptake (@muscle, @liver): stoichiometry O2_b → O2_m — Matches literature; Vf 0.8 (liver), 3.2 in muscle — Not directly comparable (an artificial capillary-delivery stand-in; muscle's ×4 so its transport does not bind before whole-body delivery does — ~4.1 mmol O₂/kg/min at the blood O₂ of hard exercise, against the ~3.7 averaged over all muscle at the whole-body ceiling, human muscle mitochondrial capacity ~6, and ~13–18 in fully perfused knee-extensor muscle [Andersen & Saltin 1985, J Physiol 366:233]); declared Vr 0 — Not directly comparable; Km {O2_b 0.05} — Insufficient context; inhibitors {O2_m: Ki 0.015 (liver), 0.007344 in muscle — solved so the muscle's resting uptake is unchanged, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• CO2Export (@muscle, @liver): stoichiometry CO2_m → CO2_b — Matches literature; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 10 — Not directly comparable; Km {CO2_m 0.1, CO2_b 0.1} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• CO2Removal: stoichiometry ∅ → CO2_b — Matches literature; Vf 0.183204 — Not directly comparable (re-expressed ×1.080 from 0.12 for the full-mass tissues, re-anchored ×1.424 to 0.18447 after the liver's per-kg recalibration, then ×1.062 after the muscle's and ×0.981 after the liver follow-up, then ×0.930 when muscle began burning fat (OPEN-WORK 2.1a): resting muscle RQ fell from ~0.99 to ~0.81; then ×1.0257 to 0.183204 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — Not directly comparable; Keq 1.2 — Insufficient context; Haldane-derived Vr used 0.183204 — Not directly comparable; Km {CO2_b 1.2} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlucoseTransport_c_to_b (@muscle): stoichiometry GLC_c → GLC_b — Matches literature; Vf 0.00036 — Not directly comparable (cut ×0.12 from 0.004, which ran ~70% saturated and took up ~10× the measured resting leg glucose uptake [42]; ~9 µmol/kg/min against ~7 while the muscle had no fat oxidation; then ×0.75 when muscle began burning fat (OPEN-WORK 2.1a) to the measured ~7 µmol/kg/min [42] — resting uptake is transport-limited, so the capacity sets it); declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.00036 — Not directly comparable; Km {GLC_c 5, GLC_b 5} — Insufficient context; activators {INS_b: Ka 100, Hill n 2, maximum fold 6} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• InsulinSecretion: stoichiometry ∅ → INS_b — Not directly comparable; Vf 0.6 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {INS_b 1} — No reliable literature value found; activators {GLC_b: Ka 5, Hill n 2, maximum fold 8} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• InsulinClearance: stoichiometry INS_b → ∅ — Not directly comparable; Vf 10 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {INS_b 100} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlucagonSecretion: stoichiometry ∅ → GCG_b — Not directly comparable; Vf 2.5 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {GCG_b 1} — No reliable literature value found; inhibitors {GLC_b: Ki 5, Hill n 2} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlucagonClearance: stoichiometry GCG_b → ∅ — Not directly comparable; Vf 5 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {GCG_b 50} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• G6PDehydrogenase (@muscle): stoichiometry G6P_c + NADP_c → P6GL_c + NADPH_c + H_c — Matches literature; Vf 0.008 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {G6P_c 0.067, NADP_c 0.0037} — Matches literature; inhibitors {NADPH_c: Ki 0.0031, Hill n 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• G6PDehydrogenase (@liver): stoichiometry G6P_c + NADP_c → P6GL_c + NADPH_c + H_c — Matches literature; Vf 0.01 — Not directly comparable (cut from a "major producer" scale to near muscle's own low-capacity level -- see the deliberate-departures note below); declared Vr 0 — Not directly comparable; Km {G6P_c 0.067, NADP_c 0.0037} — Matches literature; inhibitors {NADPH_c: Ki 0.0031, Hill n 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Phosphogluconolactonase (@muscle, @rbc): stoichiometry P6GL_c + H2O_c → P6G_c + H_c — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {P6GL_c 0.02, H2O_c 1} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PhosphogluconateDehydrogenase (@muscle, @rbc): stoichiometry P6G_c + NADP_c → Ru5P_c + CO2_b + NADPH_c — Matches literature; Vf 0.05 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {P6G_c 0.03, NADP_c 0.004} — Matches literature; inhibitors {NADPH_c: Ki 0.0031, Hill n 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PhosphogluconateDehydrogenase (@liver): stoichiometry P6G_c + NADP_c → Ru5P_c + CO2_b + NADPH_c — Matches literature; Vf 0.01 — Not directly comparable (calibration-capped, see G6PDehydrogenase @liver above); declared Vr 0 — Not directly comparable; Km {P6G_c 0.03, NADP_c 0.004} — Matches literature; inhibitors {NADPH_c: Ki 0.0031, Hill n 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• NADPHConsumption_liver (@liver): stoichiometry NADPH_c + (−1) H_c → NADP_c — Not directly comparable (the proton integer is set by the reference forms (OPEN-WORK 5.1): NADPH⁴⁻ + H⁺ → NADP³⁻ + 2[H], the convention GlutathioneReductase uses); Vf 0.0000015 — No reliable literature value found (set so the resting NADPH/NADP⁺ settles near 0.9 — measured at the true rest, ~15 h in, since the hepatic NADP(H) pool turns over that slowly; a labeled modeling device standing in for unmodeled hepatic lipogenesis/cholesterol synthesis, see the deliberate-departures note below); declared Vr 0 — No reliable literature value found; Km {NADPH_c 0.05} — No reliable literature value found; activators {INS_b: Ka 40, Hill n 2, maximum fold 3 — real hepatic lipogenesis is insulin-driven (SREBP-1c)} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• RibosePhosphateIsomerase (@muscle, @liver, @rbc): stoichiometry Ru5P_c → R5P_c — Matches literature; Vf 0.5 — Not directly comparable (set high so the step is never rate-limiting; the resting PPP flux is governed by G6PD); Keq 1.2 (R5P/Ru5P) — Matches literature [27] (measured at 38 °C, pH 7.0, 1 mM free Mg²⁺; older room-temperature, Mg-free measurements give ~3); Km {Ru5P_c 0.5, R5P_c 0.5} — No reliable literature value found (first-pass; no human-erythrocyte Km table was obtainable, and the measured constants found are bacterial); configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• RibulosePhosphateEpimerase (@muscle, @liver, @rbc): stoichiometry Ru5P_c → X5P_c — Matches literature; Vf 0.5 — Not directly comparable (not rate-limiting, see above); Keq 1.82 (X5P/Ru5P) — Matches literature [27] (same conditions; other measurements range 1.4–2.2); Km {Ru5P_c 0.5, X5P_c 0.5} — No reliable literature value found (first-pass; the measured constant found, 0.22 mM, is from spinach and is not adopted); configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• TransketolaseI (@muscle, @liver, @rbc): stoichiometry X5P_c + R5P_c → S7P_c + GAP_c — Insufficient context; Vf 0.5 — Not directly comparable; Keq 1.2 — Insufficient context (traces to early Racker/Horecker equilibria of about 1; the secondary tables that list these do not preserve each quotient's direction, so it is not re-confirmed); Km {X5P_c 0.2, R5P_c 0.4, S7P_c 0.2, GAP_c 0.1} — No reliable literature value found (first-pass); configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable. The two transketolase steps are one enzyme acting twice, written as two reactions because the engine keys on reaction name.
• Transaldolase (@muscle, @liver, @rbc): stoichiometry S7P_c + GAP_c → E4P_c + F6P_c — Insufficient context; Vf 0.5 — Not directly comparable; Keq 1.05 — Insufficient context (matches the Venkataraman & Racker 1961 value at 37 °C, pH 7.4, no Mg²⁺; not re-confirmed against a same-direction physiological-condition measurement); Km {S7P_c 0.2, GAP_c 0.1, E4P_c 0.1, F6P_c 0.3} — No reliable literature value found (first-pass); configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• TransketolaseII (@muscle, @liver, @rbc): stoichiometry X5P_c + E4P_c → F6P_c + GAP_c — Insufficient context; Vf 0.5 — Not directly comparable; Keq 10 — Insufficient context (near the Datta & Racker 1961 value of ~11.9 at 25 °C, pH 7.6; not re-confirmed); Km {X5P_c 0.2, E4P_c 0.1, F6P_c 0.3, GAP_c 0.1} — No reliable literature value found (first-pass); configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• R5PNucleotideDrain (@muscle, @liver): stoichiometry R5P_c → ∅ — Not directly comparable (a labeled artificial boundary standing in for unmodeled de-novo nucleotide synthesis via PRPP); Vf 0.002 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {R5P_c 0.05} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

• R5PNucleotideDrain (@rbc): stoichiometry R5P_c → ∅ — Not directly comparable (a labeled artificial boundary standing in for unmodeled de-novo nucleotide synthesis via PRPP); Vf 0.0001 — No reliable literature value found (×0.05 in the red cell, which makes no nucleotides de novo -- only PRPP for salvage; at the shared value it took ~18% of the cell's glucose carbon); declared Vr 0 — No reliable literature value found; Km {R5P_c 0.05} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlutathioneReductase (@muscle, @rbc): stoichiometry GSSG_c + NADPH_c + H_c → 2 GSH_c + NADP_c — Matches literature; Vf 1 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {GSSG_c 0.065, NADPH_c 0.0085} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlutathionePeroxidase (@muscle, @rbc): stoichiometry 2 GSH_c + H2O2_c → GSSG_c + 2 H2O_c — Not directly comparable; Vf 5 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {GSH_c 1.33, H2O2_c 0.005} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BasalROSProduction (@muscle): stoichiometry ∅ → H2O2_c — Matches literature; Vf 1e-06 — Not directly comparable; declared Vr 0 — Not directly comparable; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• OxidativeChallenge (@muscle, @rbc): stoichiometry ∅ → H2O2_c — Matches literature; Vf 0 — Not directly comparable; declared Vr 0 — Not directly comparable; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Catalase (@muscle, @rbc): stoichiometry H2O2_c → H2O_c + 0.5 O2_b — Matches literature; Vf 0.2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {H2O2_c 1} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• MalicEnzyme_c (@muscle): stoichiometry MAL_c + NADP_c → PYR_c + CO2_b + NADPH_c — Matches literature; Vf 0.2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {MAL_c 1, NADP_c 0.005} — Insufficient context; inhibitors {NADPH_c: Ki 0.0003, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• CitrateMalateCarrier (@muscle): stoichiometry CIT_m + MAL_c → CIT_c + MAL_m — Matches literature (the citrate/malate antiport mechanism); Vf 0.3 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Matches literature (electroneutral antiport, no chemistry); Haldane-derived Vr used 0.3 — Not directly comparable; Km {CIT_m 0.5, MAL_c 0.4, CIT_c 0.1, MAL_m 0.4} — Insufficient context; inhibitors {NADPH_c: Ki 0.001, Hill n 2} — No reliable literature value found (a labeled modeling device, not a real regulatory mechanism of SLC25A1 -- see the deliberate-departures note); configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• Aconitase_c (@muscle): stoichiometry CIT_c → ICIT_c — Matches literature; Vf 0.3 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.0666667 — Matches literature (same value as the matrix Aconitase, isoform-independent thermodynamics); Haldane-derived Vr used 4.5 — Not directly comparable; Km {CIT_c 0.08, ICIT_c 0.08} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• IsocitrateDehydrogenase_c (@muscle): stoichiometry ICIT_c + NADP_c → AKG_c + CO2_b + NADPH_c — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): no net proton, as the matrix isoform); Vf 0.2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {ICIT_c 0.065, NADP_c 0.049} — Insufficient context; inhibitors {NADPH_c: Ki 0.0003, Hill n 2, AKG_c: Ki 0.6, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycogenPhosphorylase (@liver): stoichiometry GLY_c + Pi_c → G1P_c — Matches literature; Vf 0.35 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {GLY_c 2, Pi_c 5, G1P_c 0.05} — Insufficient context; inhibitors {ATP_c: Ki 4, Hill n 2, G6P_c: Ki 0.5, Hill n 2, INS_b: Ki 13, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 10)} — Insufficient context; activators {AMP_c: Ka 0.05, Hill n 2, maximum fold 1.15 — the liver isozyme's weak AMP response [37]; GCG_b: Ka 18.75, Hill n 2, maximum fold 4 (post-absorptive re-anchor, liver follow-up: was 30) — a lumped stand-in for the glucagon/PKA cascade} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• UGPase (@liver): stoichiometry G1P_c + UTP_c → UDPGlc_c + 2 Pi_c — Matches literature; Vf 4 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {G1P_c 0.1, UTP_c 0.1} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycogenSynthase (@liver): stoichiometry UDPGlc_c → GLY_c + UDP_c + H_c — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): UDP-glucose²⁻ → glycogen + UDP³⁻ + H⁺); Vf 0.0055 — Not directly comparable (see @muscle above for the calibration finding; the liver keeps the pre-cut value); declared Vr 0 — Not directly comparable; Km {UDPGlc_c 0.2, GLY_c 50} — Insufficient context; inhibitors {AMP_c: Ki 0.05, Hill n 2, GCG_b: Ki 15, Hill n 2 — glucagon/PKA inactivation of hepatic glycogen synthase [4], added in the liver follow-up} — Insufficient context; activators {G6P_c: Ka 0.5, Hill n 1.5, maximum fold 4, INS_b: Ka 32.5, Hill n 2, maximum fold 4 (post-absorptive re-anchor, liver follow-up: was 25)} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• NucleosideDiphosphateKinase (@liver): stoichiometry UDP_c + ATP_c → UTP_c + ADP_c — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Matches literature; Haldane-derived Vr used 2 — Not directly comparable; Km {UDP_c 0.05, ATP_c 0.5, UTP_c 0.05, ADP_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Hexokinase (@liver): stoichiometry GLC_c + ATP_c → G6P_c + ADP_c + H_c — Not directly comparable (idled, Vf 0 -- the liver runs Glucokinase instead, below); declared Vr 0 — Not directly comparable; Km {GLC_c 0.05, ATP_c 0.5, G6P_c 0.05, ADP_c 0.5} — Insufficient context; inhibitors {G6P_c: Ki 0.05, Hill n 1.2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Glucokinase (@liver): stoichiometry GLC_c + ATP_c → G6P_c + ADP_c + H_c — Matches literature; Vf 0.0273 — Not directly comparable (the GKRP-sequestered floor; ~0.11 when fully fed through the insulin activator, the previous ungated 0.12); declared Vr 0 — Not directly comparable; Km {GLC_c 10, ATP_c 0.5, G6P_c 0.05, ADP_c 0.5} — Matches literature (GLC_c Km; the other two are inert Michaelis-Menten leftovers unused by this irreversible reaction, kept for parity with the enzyme it replaces); inhibitors {GCG_b: Ki 12, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 35; GKRP sequestration set to the measured cycling)} — Insufficient context; activators {INS_b: Ka 65, Hill n 2, maximum fold 5 (post-absorptive re-anchor, liver follow-up: was 50)} — Insufficient context (a lumped stand-in for GKRP release/sequestration; fasting glucose cycling ~16% vs 14% measured [34]); configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PFK1 (@liver): stoichiometry F6P_c + ATP_c → F16BP_c + ADP_c + H_c — Matches literature; Vf 0.4 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {F6P_c 0.1, ATP_c 0.3} — Insufficient context; inhibitors {ATP_c: Ki 2, Hill n 2, H_c: Ki 0.0001, Hill n 2.5} — Insufficient context; activators {AMP_c: Ka 0.1, Hill n 2, maximum fold 10, F26BP_c: Ka 0.015, Hill n 2, maximum fold 4} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateKinase (@liver): stoichiometry PEP_c + ADP_c + H_c → PYR_c + ATP_c — Matches literature; Vf 1.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {PEP_c 0.08, ADP_c 0.15, H_c 0.0001} — Insufficient context; inhibitors {ATP_c: Ki 2, Hill n 2, GCG_b: Ki 7.5, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 12)} — Insufficient context; activators {F16BP_c: Ka 0.05, Hill n 2, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• LactateTransport_c_to_b (@liver): stoichiometry LAC_c + H_c → LAC_b + H_b — Not directly comparable; Vf 1.4 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 2.5 — Insufficient context; Haldane-derived Vr used 0.56 — Not directly comparable; Km {LAC_c 1, LAC_b 1} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Cataplerosis (@liver): stoichiometry CIT_m → ∅ — Matches literature; Vf 0 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {CIT_m 0.5} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• CitrateSynthase (@liver): stoichiometry AcCoA_m + OAA_m → CIT_m + CoA_m + H_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): AcCoA⁴⁻ + OAA²⁻ + H₂O → citrate³⁻ + CoA⁴⁻ + H⁺ -- the thioester hydrolysis releases one proton; Alberty 2003); Vf 24 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {AcCoA_m 0.01, OAA_m 0.005, CoA_m 0.05} — Insufficient context; inhibitors {CIT_m: Ki 5, Hill n 2, CIT_m: Ki 1, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PyruvateCarboxylase_GNG (@liver): stoichiometry PYR_m + CO2_m + ATP_m → OAA_m + ADP_m + Pi_m + 2 H_m — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): as the shared carboxylase); Vf 0.186 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {PYR_m 0.08, CO2_m 0.02, ATP_m 0.08} — Insufficient context; inhibitors {INS_b: Ki 32.5, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 25), CIT_m: Ki 3, Hill n 2} — Insufficient context; activators {GCG_b: Ka 18.75, Hill n 2, maximum fold 6 (post-absorptive re-anchor, liver follow-up: was 30), AcCoA_m: Ka 0.08, Hill n 1.8, maximum fold 2} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• PEPCK_m (@liver): stoichiometry OAA_m + ATP_m → PEP_m + ADP_m + CO2_m — Matches literature; Vf 2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {OAA_m 0.008, ATP_m 0.1} — Insufficient context; inhibitors {INS_b: Ki 13, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 10)} — Insufficient context; activators {GCG_b: Ka 18.75, Hill n 1.5, maximum fold 4 (post-absorptive re-anchor, liver follow-up: was 30)} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• PEP_Carrier (@liver): stoichiometry PEP_m → PEP_c — Matches literature; Vf 30 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 30 — Not directly comparable; Km {PEP_m 0.05, PEP_c 0.05} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• FructoseBisphosphatase1 (@liver): stoichiometry F16BP_c + H2O_c → F6P_c + Pi_c — Matches literature; Vf 0.15 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {F16BP_c 0.02, H2O_c 1} — Insufficient context; inhibitors {F26BP_c: Ki 0.002, Hill n 2, AMP_c: Ki 0.05, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Glucose6Phosphatase (@liver): stoichiometry G6P_c + H2O_c → GLC_c + Pi_c — Matches literature; Vf 0.12 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {G6P_c 0.2, H2O_c 1} — Insufficient context; inhibitors {INS_b: Ki 130, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 100)} — Insufficient context; activators {GCG_b: Ka 18.75, Hill n 1.5, maximum fold 3 (post-absorptive re-anchor, liver follow-up: was 30)} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• F26BP_Synthesis (@liver): stoichiometry F6P_c + ATP_c → F26BP_c + ADP_c + H_c — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): F6P²⁻ + ATP⁴⁻ → F26BP⁴⁻ + ADP³⁻ + H⁺, as PFK-1); Vf 0.3 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {F6P_c 0.1, ATP_c 0.3} — Insufficient context; inhibitors {GCG_b: Ki 18.75, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 30), F26BP_c: Ki 0.03, Hill n 2} — Insufficient context; activators {INS_b: Ka 130, Hill n 2, maximum fold 5 (post-absorptive re-anchor, liver follow-up: was 100)} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• F26BP_Degradation (@liver): stoichiometry F26BP_c + H2O_c → F6P_c + Pi_c — Matches literature; Vf 0.6 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {F26BP_c 0.01, H2O_c 1} — Insufficient context; activators {GCG_b: Ka 18.75, Hill n 2, maximum fold 5 (post-absorptive re-anchor, liver follow-up: was 30)} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycerolSupply: stoichiometry ∅ → GLYC_b — Not directly comparable; Vf 0.000126735 — No reliable literature value found (calibrated numerically so resting blood glycerol settles near ~0.06 mM against GlycerolKinase's draw; re-expressed ×0.6429 from 0.000191 when the liver went to its full real mass; re-anchored ×1.0326 when muscle began burning fat (OPEN-WORK 2.1a); then ×1.0001 to 0.000126735 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; inhibitors {GLYC_b: Ki 0.1, Hill n 2; INS_b: Ki 40, Hill n 2} — No reliable literature value found; activators {GCG_b: Ka 30, Hill n 2, maximum fold 3 — the same adipose lipolytic event FattyAcidSupply stands in for} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlycerolKinase (@liver): stoichiometry GLYC_b + ATP_c → G3P_c + ADP_c + H_c — Matches literature (the integer protons are audited against the species' reference forms (OPEN-WORK 5.4): glycerol + ATP⁴⁻ → G3P²⁻ + ADP³⁻ + H⁺); Vf 0.005 — Not directly comparable (a liver-cytosol-normalised rate; a naive blood/cytosol volume match against GlycerolSupply overshoots what the liver's pyruvate/citrate sinks can absorb at rest, so this is calibrated well under that naive value -- see the code comment); declared Vr 0 — Not directly comparable; Km {GLYC_b 0.1, ATP_c 0.1} — Insufficient context; configuration {reversible no, charge 0, home c, phosphate-proton tracking no} — Not directly comparable.
• AlanineSupply: stoichiometry ∅ → ALA_b — Not directly comparable; Vf 0.000192162 — No reliable literature value found (×1.51 after the liver follow-up opened alanine transaminase at rest; calibrated numerically so resting blood alanine settles near ~0.44 mM against AlanineTransaminase's draw; re-expressed ×0.6429 from 0.00021 when the liver went to its full real mass; re-anchored ×1.0081 when muscle began burning fat (OPEN-WORK 2.1a); then ×1.00003 to 0.000192162 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; inhibitors {ALA_b: Ki 0.5, Hill n 2; INS_b: Ki 40, Hill n 2} — No reliable literature value found; activators {GCG_b: Ka 30, Hill n 2, maximum fold 3 — the glucose-alanine cycle's fasting/exercise mobilisation} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AlanineTransaminase (@liver): stoichiometry ALA_b → PYR_c — Does not match literature (lumped; the real reaction is ALA + AKG ⇌ PYR + GLU, see the deliberate-departures note above); Vf 0.005 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {ALA_b 1} — Insufficient context; inhibitors {INS_b: Ki 52, Hill n 2 (post-absorptive re-anchor, liver follow-up: was 40)} — Insufficient context; activators {GCG_b: Ka 18.75, Hill n 1.5, maximum fold 3 (post-absorptive re-anchor, liver follow-up: was 30)} — Insufficient context; configuration {reversible no, charge 0, home c, phosphate-proton tracking no} — Not directly comparable.
• FattyAcidSupply: stoichiometry ∅ → FA_b — Not directly comparable; Vf 0.00647388 — No reliable literature value found (originally 0.0020187, calibrated so the net hormone multiplier at the resting poise reproduced the previous 0.0015 supply; re-expressed ×0.6429 when its only consumer, the liver, went to its full real mass; re-anchored ×2.99 when the liver's O₂ use — ~3/4 of it from fat — was brought to its literature rate; re-anchored ×1.678 when muscle began burning fat (OPEN-WORK 2.1a) — muscle now draws blood fatty acid for ~55% of its resting O₂; then ×0.9930 to 0.00647388 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): re-anchored); declared Vr 0 — No reliable literature value found; inhibitors {FA_b: Ki 0.4, Hill n 2; INS_b: Ki 40, Hill n 2 — insulin is the dominant antilipolytic signal} — No reliable literature value found; activators {GCG_b: Ka 30, Hill n 2, maximum fold 3 — glucagon/fasting lipolytic drive} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BetaOxidation (@liver): stoichiometry FA_b + CoA_m + NAD_m + FAD_m + H2O_m → AcCoA_m + NADH_m + FADH2_m + H_m — Not directly comparable; Vf 0.2 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {FA_b 0.1, CoA_m 0.1, NAD_m 0.1, FAD_m 0.05} — Insufficient context; inhibitors {INS_b: Ki 40, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• BetaOxidation (@muscle): stoichiometry as @liver — Not directly comparable; Vf 0.02 (0.002 × 10 per liter of matrix) — Not directly comparable (FIRST-PASS, calibrated to the resting fuel mix: muscle RQ ~0.81, ~55% of resting O₂ from fat, against a lean human leg RQ of 0.83 and 59% [81] and a forearm RQ of ~0.76 [82]; the liver's copy runs 0.2 with 3× the mitochondria: at rest a hepatocyte burns ~25× the fat per kg); declared Vr 0 — Not directly comparable; Km as @liver — Insufficient context; inhibitors {INS_b: Ki 40, Hill n 2 — the CPT1/malonyl-CoA abstraction the liver's copy carries; hyperinsulinemia with hyperglycemia cuts human leg long-chain fat oxidation ~80% [83], and at the model pancreas's ~90 pM ceiling this gate gives ~72%} — Insufficient context; activators {Ca_c: Ka 0.0002, Hill n 2, maximum fold 6 — contraction-induced fatty-acid uptake (CD36 translocation, falling malonyl-CoA), the phosphorylase-kinase constants; FIRST-PASS fold, sized so the muscle draws what the adipose stand-in can supply} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• Thiolase (@liver): stoichiometry 2 AcCoA_m → AcAcCoA_m + CoA_m — Not directly comparable; Vf 10 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 0.02 — Does not match literature (first-pass; the measured synthesis equilibrium is ~1e-5, see deliberate departures above); Haldane-derived Vr used 5.55556 — Not directly comparable; Km {AcCoA_m 0.3, AcAcCoA_m 0.02, CoA_m 0.05} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• HMGCoASynthase (@liver): stoichiometry AcAcCoA_m + AcCoA_m + H2O_m → HMGCoA_m + CoA_m + H_m — Not directly comparable (the proton integers are audited against the species' reference forms, OPEN-WORK 5.4: AcAcCoA⁴⁻ + AcCoA⁴⁻ + H₂O → HMG-CoA⁵⁻ + CoA⁴⁻ + H⁺; the acetyl-CoA thioester hydrolysis releases one); Vf 6 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {AcAcCoA_m 0.02, AcCoA_m 0.3, H2O_m 1} — Insufficient context; inhibitors {INS_b: Ki 35, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• HMGCoALyase (@liver): stoichiometry HMGCoA_m → AcAc_m + AcCoA_m — Not directly comparable; Vf 3 — Not directly comparable (retuned 10x slower than an initial 30, a numerical-conditioning fix, not a biological one: HMG-CoA's own quasi-steady-state relative to this Km was thousands of times faster than the live simulation path's ~0.1 s reporting frame, so the chunked solver could overshoot it below zero on every restart; the net ketogenesis flux, which this pass-through step does not control, is unaffected); declared Vr 0 — Not directly comparable; Km {HMGCoA_m 0.02} — Insufficient context; configuration {reversible no, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• BDH (@liver): stoichiometry AcAc_m + NADH_m + H_m → BHB_m + NAD_m — Matches literature; Vf 20 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 20.3 — Insufficient context; Haldane-derived Vr used 9.8522167 — Not directly comparable; Km {AcAc_m 0.1, NADH_m 0.05, BHB_m 0.1, NAD_m 0.5} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• AcetoacetateExport (@liver): stoichiometry AcAc_m → AcAc_b — Matches literature; Vf 15 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 15 — Not directly comparable; Km {AcAc_m 0.2, AcAc_b 0.2} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• BHBExport (@liver): stoichiometry BHB_m → BHB_b — Matches literature; Vf 15 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 15 — Not directly comparable; Km {BHB_m 0.2, BHB_b 0.2} — Insufficient context; configuration {reversible yes, charge 0, home m, phosphate-proton tracking no} — Not directly comparable.
• AcetoacetateDisposal: stoichiometry AcAc_b + H_b → ∅ — Matches literature (oxidizing a ketone anion takes up a proton, the bicarbonate the kidney and muscle regenerate; OPEN-WORK 5.1); Vf 0.000387545 — Not directly comparable (re-expressed ×0.6429 from 0.0005 with its only producer, the full-mass liver; re-anchored ×0.533, one scale for both disposals, after the liver's per-kg recalibration to 0.00017117, then ×0.883 after the muscle's, whose glycerol-3-phosphate shuttle fix also reduced the liver cytosol, then ×0.860 after the liver follow-up and ×0.774 after the red-cell stage, then ×0.842 when muscle began burning fat (OPEN-WORK 2.1a): with blood glucose ~2% higher, insulin is slightly higher and the liver makes a little less ketone, then ×1.0035 after the proton integers were audited and corrected (OPEN-WORK 5.4), one scale for both; then ×4.558 to 0.000387545 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): the extra lactate the liver now oxidizes feeds its acetyl-CoA and raised resting ketogenesis about 4-fold, which this artificial disposal balances (one scale for both disposals); the liver's pyruvate split and ketogenic gating, which a real liver would carry, are an open item); declared Vr 0 — Not directly comparable; Km {AcAc_b 0.2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BHBDisposal: stoichiometry BHB_b + H_b → ∅ — Matches literature (as acetoacetate; OPEN-WORK 5.1); Vf 0.000387545 — Not directly comparable (re-expressed ×0.6429 from 0.0005 with its only producer, the full-mass liver; re-anchored ×0.533, one scale for both disposals, after the liver's per-kg recalibration to 0.00017117, then ×0.883 after the muscle's, whose glycerol-3-phosphate shuttle fix also reduced the liver cytosol, then ×0.860 after the liver follow-up and ×0.774 after the red-cell stage, then ×0.842 when muscle began burning fat (OPEN-WORK 2.1a): with blood glucose ~2% higher, insulin is slightly higher and the liver makes a little less ketone, then ×1.0035 after the proton integers were audited and corrected (OPEN-WORK 5.4), one scale for both; then ×4.558 to 0.000387545 with the measured LDH, enolase and PGM equilibrium constants (OPEN-WORK 4.3): one scale for both disposals, as above); declared Vr 0 — Not directly comparable; Km {BHB_b 0.2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlucoseTransport_c_to_b (@liver): stoichiometry GLC_c → GLC_b — Matches literature; Vf 0.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.5 — Not directly comparable; Km {GLC_c 17, GLC_b 17} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• Hexokinase (@rbc): stoichiometry GLC_c + ATP_c → G6P_c + ADP_c + H_c — Matches literature; Vf 0.01407 — Matches literature (the measured red-cell activity, 1.78 IU/g Hb [56]); declared Vr 0 — Not directly comparable; Km {GLC_c 0.05, ATP_c 0.5, G6P_c 0.05, ADP_c 0.5} — Insufficient context; inhibitors {G6P_c: Ki 0.015, Hill n 1, BPG23_c: Ki 4, Hill n 1, GSH_c: Ki 3, Hill n 1 — the erythrocyte hexokinase's (HK1) product inhibition and its 2,3-BPG and glutathione inhibitors [57]; first-pass constants within their reported orders} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PFK1 (@rbc): stoichiometry F6P_c + ATP_c → F16BP_c + ADP_c + H_c — Matches literature; Vf 0.08702 — Matches literature (the measured red-cell activity, 11.01 IU/g Hb [56]); declared Vr 0 — Not directly comparable; Km {F6P_c 0.1, ATP_c 0.3} — Insufficient context; inhibitors {ATP_c: Ki 2, Hill n 2, H_c: Ki 0.0001, Hill n 2.5, BPG23_c: Ki 0.5, Hill n 1 — 2,3-BPG feedback [57], first-pass, set so PFK runs at ~1% of its measured capacity as in the intact cell} — Insufficient context; activators {AMP_c: Ka 0.1, Hill n 2, maximum fold 10, F26BP_c: Ka 0.015, Hill n 2, maximum fold 4} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• GlucoseTransport_c_to_b (@rbc): stoichiometry GLC_c → GLC_b — Matches literature; Vf 0.5 — Not directly comparable; declared Vr 0 — Not directly comparable; Keq 1 — Insufficient context; Haldane-derived Vr used 0.5 — Not directly comparable; Km {GLC_c 1.5, GLC_b 1.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• ATPConsumption (@rbc): stoichiometry ATP_c + H2O_c → ADP_c + Pi_c + H_c — Not directly comparable; Vf 0.00084 — No reliable literature value found (an artificial demand; raised from 0.0006 in the red-cell stage to ~2.2 mmol ATP per L of cells per hour, the net yield of the measured glucose use through glycolysis less the 2,3-BPG shunt); declared Vr 0 — No reliable literature value found; Km {ATP_c 0.2, H2O_c 1, ADP_c 0.2, Pi_c 0.2, H_c 0.0001} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• PhosphateSupply (@rbc): stoichiometry ∅ → Pi_c — Not directly comparable; Vf 0.1 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Keq 1 — No reliable literature value found; Haldane-derived Vr used 0.01 — Not directly comparable; Km {Pi_c 0.1} — No reliable literature value found; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• AdenylateKinase_c (@rbc): stoichiometry ATP_c + AMP_c → 2 ADP_c — Matches literature; Vf 2.039 — Matches literature (the measured red-cell activity, 258 IU/g Hb at 37 °C [56]); declared Vr 0 — Not directly comparable; Keq 2.2727273 — Matches literature; Haldane-derived Vr used 4.486 — Not directly comparable; Km {ATP_c 0.5, AMP_c 0.1, ADP_c 0.5} — Insufficient context; configuration {reversible yes, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• NADPHConsumption (@rbc): stoichiometry NADPH_c + (−1) H_c → NADP_c — Not directly comparable (the proton integer is set by the reference forms (OPEN-WORK 5.1): as the liver's twin); Vf 0.0001 — No reliable literature value found; declared Vr 0 — No reliable literature value found; Km {NADPH_c 0.05} — No reliable literature value found; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BisphosphoglycerateMutase (@rbc): stoichiometry BPG13_c → BPG23_c + H_c — Matches literature (BPG13⁴⁻ → BPG23⁵⁻ + H⁺; with the phosphatase the shunt then costs the proton PGK's ATP-forming step would have taken up; 2,3-BPG is not a buffering species in the pH inversion, so the proton goes straight to the free pool; OPEN-WORK 5.1); Vf 0.02 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {BPG13_c 0.05} — Insufficient context; inhibitors {BPG23_c: Ki 4.5, Hill n 2} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BisphosphoglyceratePhosphatase (@rbc): stoichiometry BPG23_c + H2O_c → PG3_c + Pi_c — Matches literature; Vf 0.0006 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {BPG23_c 5, H2O_c 1} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• G6PDehydrogenase (@rbc): stoichiometry G6P_c + NADP_c → P6GL_c + NADPH_c + H_c — Matches literature; Vf 0.05 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {G6P_c 0.067, NADP_c 0.0037} — Matches literature; inhibitors {NADPH_c: Ki 0.0031, Hill n 2} — Matches literature; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• BasalROSProduction (@rbc): stoichiometry ∅ → H2O2_c — Matches literature; Vf 5e-05 — Not directly comparable; declared Vr 0 — Not directly comparable; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.
• HemoglobinOxidation (@rbc): stoichiometry Hb_c + H2O2_c → HbOx_c + H2O_c — Matches literature; Vf 0.1 — Not directly comparable; declared Vr 0 — Not directly comparable; Km {Hb_c 5, H2O2_c 0.02} — Insufficient context; configuration {reversible no, charge 0, home inferred, phosphate-proton tracking no} — Not directly comparable.

Initial-condition register

Every literature starting value follows — the anchors the resting seed is built from (see Starting concentrations); the seeded rest itself is a model output and is not registered. Labels describe evidential comparability of the numerical start state, not whether the metabolite itself is physiological.

Shared/blood

• LAC_b = 0 mM — Insufficient context.
• GLC_b = 5 mM — Insufficient context.
• INS_b = 40 mM — Insufficient context.
• GCG_b = 17 mM — Insufficient context.
• O2_b = 0.1 mM — Insufficient context.
• CO2_b = 1 mM — Insufficient context.
• H_b = 3.98e-05 mM — Matches literature.
• Buffer_b = 16 mM — Insufficient context.
• BufferH_b = 8 mM — Insufficient context.
• FA_b = 0.4 mM — Insufficient context.
• AcAc_b = 0.05 mM — Insufficient context.
• BHB_b = 0.1 mM — Insufficient context.
• GLYC_b = 0.05 mM — Matches literature (fasting-human arterial glycerol, ~0.03-0.1 mM).
• ALA_b = 0.4 mM — Matches literature (fasting-human plasma alanine, ~0.3-0.45 mM).

Muscle

• GLY_muscle_c = 220 mM — Matches literature (~100 mmol glucosyl units per kg wet muscle, the 1.5–1.8 g/100 g of resting human muscle on a mixed diet [45], in per-liter-of-cytosol units; was 80).
• G1P_muscle_c = 0 mM — Insufficient context.
• UTP_muscle_c = 0.2 mM — Insufficient context.
• UDP_muscle_c = 0.01 mM — Insufficient context.
• UDPGlc_muscle_c = 0.3 mM — Insufficient context.
• GLC_muscle_c = 0.1 mM — Insufficient context.
• G6P_muscle_c = 0 mM — Insufficient context.
• F6P_muscle_c = 0 mM — Insufficient context.
• F16BP_muscle_c = 0 mM — Insufficient context.
• DHAP_muscle_c = 0 mM — Insufficient context.
• GAP_muscle_c = 0 mM — Insufficient context.
• G3P_muscle_c = 0.08 mM — Insufficient context.
• BPG13_muscle_c = 0 mM — Insufficient context.
• PG3_muscle_c = 0 mM — Insufficient context.
• PG2_muscle_c = 0 mM — Insufficient context.
• PEP_muscle_c = 0 mM — Insufficient context.
• PYR_muscle_c = 0 mM — Insufficient context.
• ATP_muscle_c = 8 mM — Matches literature.
• ADP_muscle_c = 0.015 mM — Insufficient context.
• AMP_muscle_c = 0.002 mM — Insufficient context.
• PCr_muscle_c = 30 mM — Matches literature.
• Cr_muscle_c = 10 mM — Insufficient context.
• NAD_muscle_c = 0.7 mM — Insufficient context.
• NADH_muscle_c = 0.001 mM — Insufficient context.
• LAC_muscle_c = 0 mM — Insufficient context.
• MAL_muscle_c = 0.5 mM — Insufficient context.
• OAA_muscle_c = 0.005 mM — Insufficient context.
• ASP_muscle_c = 1.5 mM — Insufficient context.
• GLU_muscle_c = 6 mM — Insufficient context.
• AKG_muscle_c = 0.1 mM — Insufficient context.
• Pi_muscle_c = 3 mM — Matches literature.
• H2O_muscle_c = 55500 mM — Insufficient context.
• H_muscle_c = 69.691435 mM — Insufficient context.
• Ca_muscle_c = 0.0001 mM — Matches literature.
• PYR_muscle_i = 0 mM — Insufficient context.
• ATP_muscle_i = 7.8 mM — Insufficient context.
• ADP_muscle_i = 0.02 mM — Insufficient context.
• Pi_muscle_i = 0.5 mM — Insufficient context.
• H_muscle_i = 68.626027 mM — Insufficient context.
• CytC_ox_muscle_i = 0.187 mM — Insufficient context.
• CytC_red_muscle_i = 0.013 mM — Insufficient context.
• PYR_muscle_m = 0.05 mM — Insufficient context.
• CoA_muscle_m = 0.6 mM — Insufficient context.
• AcCoA_muscle_m = 0.05 mM — Insufficient context.
• OAA_muscle_m = 0.005 mM — Insufficient context.
• CIT_muscle_m = 0.35 mM — Insufficient context.
• ICIT_muscle_m = 0.02 mM — Insufficient context.
• AKG_muscle_m = 0.1 mM — Insufficient context.
• SucCoA_muscle_m = 0.02 mM — Insufficient context.
• SUC_muscle_m = 0.3 mM — Insufficient context.
• FUM_muscle_m = 0.05 mM — Insufficient context.
• MAL_muscle_m = 0.5 mM — Insufficient context.
• ASP_muscle_m = 1 mM — Insufficient context.
• GLU_muscle_m = 5 mM — Insufficient context.
• ATP_muscle_m = 5.8 mM — Insufficient context.
• ADP_muscle_m = 0.2 mM — Insufficient context.
• AMP_muscle_m = 0 mM — Insufficient context.
• NAD_muscle_m = 0.42 mM — Insufficient context.
• NADH_muscle_m = 0.08 mM — Insufficient context.
• FAD_muscle_m = 0.198 mM — Insufficient context.
• FADH2_muscle_m = 0.002 mM — Insufficient context.
• CoQ_muscle_m = 1.967 mM — Insufficient context.
• CoQH2_muscle_m = 0.033 mM — Insufficient context.
• Pi_muscle_m = 5 mM — Insufficient context.
• H2O_muscle_m = 55500 mM — Insufficient context.
• H_muscle_m = 45.950042 mM — Insufficient context.
• CO2_muscle_m = 0.05 mM — Insufficient context.
• O2_muscle_m = 0.03 mM — Insufficient context.
• Ca_muscle_m = 0.0002 mM — Matches literature.
• Dpsi_muscle_m = 160 mV — Insufficient context.
• O2super_muscle_m = 0 mM — Insufficient context.
• H2O2_muscle_m = 0 mM — Insufficient context.
• NADP_muscle_c = 0.166 mM — Insufficient context.
• NADPH_muscle_c = 0.164 mM — Insufficient context.
• GSH_muscle_c = 1 mM — Insufficient context.
• GSSG_muscle_c = 0.005 mM — Insufficient context.
• P6GL_muscle_c = 0.001 mM — Insufficient context.
• P6G_muscle_c = 0.025 mM — Insufficient context.
• Ru5P_muscle_c = 0.008 mM — Insufficient context.
• H2O2_muscle_c = 1e-07 mM — Insufficient context.
• CIT_muscle_c = 0.35 mM — Insufficient context.
• ICIT_muscle_c = 0.033 mM — Insufficient context.

Liver

• GLY_liver_c = 560 mM — Matches literature (207 ± 22 mmol per liter of liver after an overnight fast, human ¹³C-MRS [35], in per-liter-of-cytosol units).
• G1P_liver_c = 0 mM — Insufficient context.
• UTP_liver_c = 0.2 mM — Insufficient context.
• UDP_liver_c = 0.01 mM — Insufficient context.
• UDPGlc_liver_c = 0.3 mM — Insufficient context.
• GLC_liver_c = 5 mM — Insufficient context.
• G6P_liver_c = 0.12 mM — Insufficient context.
• F6P_liver_c = 0.055 mM — Insufficient context.
• F16BP_liver_c = 0.01 mM — Insufficient context.
• DHAP_liver_c = 0 mM — Insufficient context.
• GAP_liver_c = 0 mM — Insufficient context.
• G3P_liver_c = 0.08 mM — Insufficient context.
• BPG13_liver_c = 0 mM — Insufficient context.
• PG3_liver_c = 0 mM — Insufficient context.
• PG2_liver_c = 0 mM — Insufficient context.
• PEP_liver_c = 0.01 mM — Insufficient context.
• PYR_liver_c = 0.04 mM — Insufficient context.
• ATP_liver_c = 4.8 mM — Matches literature.
• ADP_liver_c = 0.015 mM — Insufficient context.
• AMP_liver_c = 0.003 mM — Insufficient context.
• NAD_liver_c = 0.7 mM — Insufficient context.
• NADH_liver_c = 0.001 mM — Insufficient context.
• LAC_liver_c = 0.7 mM — Insufficient context.
• MAL_liver_c = 0.5 mM — Insufficient context.
• OAA_liver_c = 0.005 mM — Insufficient context.
• ASP_liver_c = 1.5 mM — Insufficient context.
• GLU_liver_c = 6 mM — Insufficient context.
• AKG_liver_c = 0.1 mM — Insufficient context.
• Pi_liver_c = 3 mM — Matches literature.
• H2O_liver_c = 55500 mM — Insufficient context.
• H_liver_c = 68.978518 mM — Insufficient context.
• Ca_liver_c = 0.0001 mM — Matches literature.
• PYR_liver_i = 0 mM — Insufficient context.
• ATP_liver_i = 7.8 mM — Insufficient context.
• ADP_liver_i = 0.02 mM — Insufficient context.
• Pi_liver_i = 0.5 mM — Insufficient context.
• H_liver_i = 68.626027 mM — Insufficient context.
• CytC_ox_liver_i = 0.187 mM — Insufficient context.
• CytC_red_liver_i = 0.013 mM — Insufficient context.
• PYR_liver_m = 0.05 mM — Insufficient context.
• CoA_liver_m = 0.6 mM — Insufficient context.
• AcCoA_liver_m = 0.05 mM — Insufficient context.
• OAA_liver_m = 3e-05 mM — Insufficient context (seeded at the liver's own resting level; the shared 0.005 started a citrate-synthase burst that emptied acetyl-CoA).
• CIT_liver_m = 0.35 mM — Insufficient context.
• ICIT_liver_m = 0.02 mM — Insufficient context.
• AKG_liver_m = 0.1 mM — Insufficient context.
• SucCoA_liver_m = 0.02 mM — Insufficient context.
• SUC_liver_m = 0.3 mM — Insufficient context.
• FUM_liver_m = 0.05 mM — Insufficient context.
• MAL_liver_m = 0.04 mM — Insufficient context (seeded at the liver's own resting level, with OAA_liver_m).
• ASP_liver_m = 1 mM — Insufficient context.
• GLU_liver_m = 5 mM — Insufficient context.
• ATP_liver_m = 5.8 mM — Insufficient context.
• ADP_liver_m = 0.2 mM — Insufficient context.
• AMP_liver_m = 0 mM — Insufficient context.
• NAD_liver_m = 0.42 mM — Insufficient context.
• NADH_liver_m = 0.08 mM — Insufficient context.
• FAD_liver_m = 0.198 mM — Insufficient context.
• FADH2_liver_m = 0.002 mM — Insufficient context.
• CoQ_liver_m = 1.967 mM — Insufficient context.
• CoQH2_liver_m = 0.033 mM — Insufficient context.
• Pi_liver_m = 5 mM — Insufficient context.
• H2O_liver_m = 55500 mM — Insufficient context.
• H_liver_m = 45.951679 mM — Insufficient context.
• CO2_liver_m = 0.05 mM — Insufficient context.
• O2_liver_m = 0.03 mM — Insufficient context.
• Ca_liver_m = 0.0002 mM — Matches literature.
• Dpsi_liver_m = 160 mV — Insufficient context.
• O2super_liver_m = 0 mM — Insufficient context.
• H2O2_liver_m = 0 mM — Insufficient context.
• F26BP_liver_c = 0.008 mM — Insufficient context.
• PEP_liver_m = 0.02 mM — Insufficient context.
• AcAcCoA_liver_m = 0.001 mM — Insufficient context (trace ketogenesis intermediate; seed only, settles ~1.8e-4 mM).
• HMGCoA_liver_m = 4e-05 mM — Insufficient context (trace ketogenesis intermediate; seeded near where it settles, ~3.7e-5 mM, so a run does not start by draining it below zero).
• AcAc_liver_m = 0.02 mM — Insufficient context.
• BHB_liver_m = 0.05 mM — Insufficient context.
• NADP_liver_c = 0.166 mM — Insufficient context.
• NADPH_liver_c = 0.164 mM — Insufficient context.
• P6GL_liver_c = 0.001 mM — Insufficient context.
• P6G_liver_c = 0.025 mM — Insufficient context.
• Ru5P_liver_c = 0.008 mM — Insufficient context.
• R5P_liver_c = 0.01 mM — Insufficient context.
• X5P_liver_c = 0.01 mM — Insufficient context.
• S7P_liver_c = 0.008 mM — Insufficient context.
• E4P_liver_c = 0.005 mM — Insufficient context.

Rbc

• GLC_rbc_c = 5 mM — Insufficient context.
• G6P_rbc_c = 0.074 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• F6P_rbc_c = 0.026 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• F16BP_rbc_c = 0.11 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• DHAP_rbc_c = 0.42 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• GAP_rbc_c = 0.019 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• BPG13_rbc_c = 0.0014 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• PG3_rbc_c = 0.19 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• PG2_rbc_c = 0.033 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• PEP_rbc_c = 0.015 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• PYR_rbc_c = 0.05 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• BPG23_rbc_c = 4.35 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• ATP_rbc_c = 1.73 mM — Matches literature (seeded at the cell's settled rest, red-cell stage).
• ADP_rbc_c = 0.083 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• AMP_rbc_c = 0.0017 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• NAD_rbc_c = 0.1219 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• NADH_rbc_c = 0.00013 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• LAC_rbc_c = 0.41 mM — Insufficient context (seeded at the cell's settled rest, red-cell stage).
• Pi_rbc_c = 1 mM — Matches literature.
• H2O_rbc_c = 55500 mM — Insufficient context.
• H_rbc_c = (re-seeded from the cell's phosphate pools) mM — Insufficient context.
• NADP_rbc_c = 0.166 mM — Insufficient context.
• NADPH_rbc_c = 0.164 mM — Insufficient context.
• GSH_rbc_c = 3.2 mM — Insufficient context.
• GSSG_rbc_c = 0.016 mM — Insufficient context.
• P6GL_rbc_c = 0.001 mM — Insufficient context.
• P6G_rbc_c = 0.025 mM — Insufficient context.
• Ru5P_rbc_c = 0.008 mM — Insufficient context.
• H2O2_rbc_c = 1e-07 mM — Insufficient context.
• Hb_rbc_c = 5 mM — Insufficient context.
• HbOx_rbc_c = 0 mM — Insufficient context.

Global constants, compartments, and proton bookkeeping

• Compartment-volume fractions: c 0.7, i 0.02, m 0.07, b 1; matrix capacity scale 10 — Not directly comparable (the fractions are modelling geometry; the scale is derived).
• Blood pool volume (BLOOD_POOL_VOLUME_L): one unit of b = 14 L of extracellular fluid — Matches literature (inside the 11.7–17.3 L adult-male range [28]; the point within it is a modelling choice).
• Organ sizes: skeletal muscle 29 kg, liver 1.8 kg, red cells 2.3 L — Matches literature (ICRP 89 reference adult male [28]).
• Intracellular water: skeletal muscle 0.65 L/kg [29], red cells 0.717 L per L of cells [30] — Matches literature; liver 0.50 L/kg — Insufficient context (a modelling estimate from total liver water and the extracellular/sinusoidal fraction [31]; no single human value found).
• Liver mitochondrial volume (LIVER_MITOCHONDRIAL_VOLUME_SCALE): intermembrane space + matrix 3× the reference geometry (0.06 + 0.21 of cell water, cytosol 0.70), mitochondria 28% of the modeled hepatocyte — Matches literature (22–28% by stereology [39][31], rat; human biopsies show no principal difference [40]; human vastus lateralis ~5% [41]; the point within the range is a modelling choice).
• Red-cell cytosol (RBC.cytosol_volume_scale): 1/0.70 of the reference cytosol -- all of the cell's water is cytosol, since a mature red cell has no organelles — Matches literature (no mitochondria or nucleus).
• Tissue mass factors (whole-body intracellular water ÷ pool volume): muscle 1.3464, liver 0.064286, red cells 0.11779 — Not directly comparable (derived from the three constants above).
• Thermal voltage 26.71 mV — Matches literature at the model temperature; inner-membrane capacitance 0.00675 mM charge mV⁻¹ — Insufficient context; proton reference 0.0001 mM — Not directly comparable.
• Generic intracellular buffer total 100 mM and pKa 7.3 — Matches literature at the stated reduced-model buffer-capacity level; pH inversion bounds 2–12 and tolerance 1e-13 — Not directly comparable.
• Phosphate-group pKa values: Pi 6.82, ATP 6.48, ADP 6.38, AMP 6.22, G1P 6.11, G6P 6.11, F6P 6.11, F16BP 6.05/6.65, F26BP 6.05/6.65, GAP 6.45, DHAP 6.45, G3P 6.66, BPG13 6.6, PG3 6.21, PG2 7, PEP 6.35 — Matches literature for the stated physiological-ionic-strength convention.
• Numerical guards: positivity smoothing 1e-09 (evaluated in a cancellation-free form below zero, so it never rounds to exactly 0), logarithm floor 1e-30, maximum electrical exponent 200, mechanistic-argument clamp 30 — Not directly comparable.

Register interpretation

The register is deliberately conservative. “Matches literature” means the value or relation is supportable within the explicit convention shown; it does not imply that a reduced rate law reproduces a full enzyme mechanism. “Insufficient context” means the literature contains potentially comparable numbers but Fluxion lacks one or more required qualifiers. “No reliable literature value found” is reserved mainly for artificial boundary/control capacities. “Not directly comparable” covers fitted capacities, Haldane consequences, numerical settings, and lumped reactions whose model variable is not a single measurable biochemical constant.

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