= Glycolysis cofactor recycling
In the payoff stage of <glycolysis>, <oxidation> of <glyceraldehyde 3-phosphate> is coupled to <reduction> of <NAD+>. Each <NADH> carries a two-<Electron> reducing equivalent. The formal half-<chemical equation>
$$
\mathrm{NAD}^{+}+\mathrm H^{+}+2e^-\longrightarrow\mathrm{NADH}
$$
makes the <Electron> count explicit: two <NADH> per <glucose> carry four <Electrons>. This is <redox> bookkeeping, not a claim that free <Electrons> travel through the <chemical solution> or that <NADH> is itself <ATP>.
<Fermentation> can return <NADH> to <NAD+> by reducing an organic <substrate>; reduction of <pyruvate> to <lactate> is one example. In aerobic <cellular respiration>, reducing equivalents reach an <electron transport chain>, reducing molecular <oxygen>. Other forms of <cellular respiration> use other <electron acceptors>, so absence of <oxygen> does not uniquely imply <fermentation>.<Biology 2e by Mary Ann Clark and others>[§7.2, step 6 and its NAD+ regeneration paragraph; §7.5, opening comparison of fermentation and anaerobic respiration, Lactic Acid Fermentation and Figure 7.16 caption]{ref}
\Image[/glycolysis-nad-regeneration.png]
{title=Sustained <glycolysis> needs <NAD+> regeneration and continuing <ADP> supply}
{description=Original pool-and-process schematic, not an anatomical map. <Fermentation> and respiratory <oxidation> are alternative routes for recycling reducing equivalents, not simultaneous obligatory reactions. The respiratory box groups transport and <electron transport chain> steps. The lower ledger shows two net <ATP> per <glucose>; separate <ATP> use can return <ADP> and <inorganic phosphate>. Recycling material carriers does not supply an independent source of <energy>.}
The need for <NAD+> regeneration follows from a finite-pool argument. In a hypothetical closed preparation with $12\,\mathrm{\mu mol}$ of initially oxidized <NAD+> and no regeneration, at most $6\,\mathrm{\mu mol}$ of <glucose> can complete the two <NAD+>-consuming conversions per <glucose>. This is an upper bound even with excess <glucose>, not a predicted stopping time: other limitations can stop the preparation earlier. With an intact fixed <nicotinamide adenine dinucleotide> pool and no side reactions, converting <NAD+> into <NADH> preserves their sum but depletes the usable oxidized form.
<ATP> recycling imposes a second condition. <Glycolysis> needs some initial <ATP> for investment and consumes two net <ADP> and two <inorganic phosphate> per completed <glucose>. In a closed ideal preparation with only $8\,\mathrm{\mu mol}$ of initial <ADP>, no other source of <ADP>, and enough initial <ATP> and <inorganic phosphate>, at most $4\,\mathrm{\mu mol}$ of <glucose> can finish. This bound follows from the net <ADP> consumption, even though investment temporarily produces additional <ADP>. Initial investment also means that adequate final inventories alone cannot guarantee the route can start.
For continued operation at fixed carrier inventories, other <chemical reactions> must match the two net <ATP> formed per <glucose> with <ATP> use that restores <ADP> and <inorganic phosphate>, or exchange must supply those <reactants>. <ATP> <hydrolysis> coupled to cellular work is one route. Thus <glycolysis> can sustain useful <energy coupling> while neither its <ATP> inventory nor its <NADH> inventory grows indefinitely; matter cycles while <glucose> supplies fresh chemical <free energy>.
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