The Respiratory Balance Sheet

Bringing together the ATP-equivalent yield of every stage of aerobic respiration -- glycolysis, the oxidative decarboxylation (link reaction) of pyruvic acid, the TCA cycle, and the electron transport system -- gives what is conventionally called the respiratory balance sheet: an account of the total number of ATP molecules generated from the complete oxidation of one molecule of glucose to carbon dioxide and water.

Glycolysis, occurring in the cytoplasm, yields a net two molecules of ATP by substrate-level phosphorylation (four generated, two consumed) together with two molecules of NADH, for each glucose molecule respired. The oxidative decarboxylation of the two resulting pyruvic acid molecules, occurring in the mitochondrial matrix, yields no ATP directly but generates a further two molecules of NADH. The TCA cycle, turning twice per glucose molecule (once for each of the two acetyl CoA molecules produced), yields two further molecules of ATP (as GTP) by substrate-level phosphorylation, together with six molecules of NADH and two molecules of FADH2.

Adding these together gives a total, before any contribution from the electron transport system, of four ATP captured directly by substrate-level phosphorylation, together with ten molecules of NADH and two molecules of FADH2 still carrying their electrons unused. It is the oxidation of these ten NADH and two FADH2 molecules by the electron transport system, described in the previous section, that generates by far the largest share of the total ATP yield, through oxidative phosphorylation.

Using the conventional, commonly taught conversion factors of roughly three ATP per NADH oxidised and roughly two ATP per FADH2 oxidised, the ten NADH molecules would together yield approximately 30 ATP and the two FADH2 molecules a further approximately 4 ATP, giving an oxidative-phosphorylation total of around 34 ATP; adding this to the four ATP already captured by substrate-level phosphorylation gives a widely cited overall total of approximately 36 to 38 ATP molecules generated from the complete aerobic oxidation of one glucose molecule.

This figure is deliberately given as a range rather than a single fixed number, and that is not an oversight: the exact total genuinely does vary, both between textbook conventions and, more fundamentally, for real biochemical reasons. Chief among these is that the two NADH molecules produced by glycolysis are generated in the cytoplasm, not inside the mitochondrion, and must be shuttled across the mitochondrial membrane before their electrons can be delivered to the electron transport system; depending on which of two shuttle mechanisms a particular cell uses, this cytoplasmic NADH may be effectively converted, in transit, into the mitochondrial equivalent of either NADH (via the malate-aspartate shuttle, preserving the full three-ATP yield) or FADH2 (via the glycerol-3-phosphate shuttle, reducing its yield to about two ATP), which alone can shift the grand total by two ATP. More modern, precisely measured P/O ratios (the number of ATP generated per pair of electrons, or per oxygen atom, consumed) give somewhat lower conversion factors of roughly 2.5 ATP per NADH and 1.5 ATP per FADH2, which would bring the overall total down further, to a range closer to 30 to 32 ATP. …