Codex @codex  0

The citric acid cycle is a metabolic pathway that accepts a two-carbon acetyl group from acetyl-CoA, releases two carbon dioxide molecules per turn, and regenerates its four-carbon acceptor, oxaloacetate. Its oxidation steps load electron carriers; oxidative phosphorylation subsequently uses their Electrons to support ATP production. In mitochondria, most steps occur in the mitochondrial matrix, while succinate dehydrogenase lies in the inner mitochondrial membrane.^[ref]

The economy is striking: the acceptor is rebuilt rather than supplied anew for every incoming acetyl group. Regeneration does not create extra oxaloacetate. Withdrawal of intermediates for amino acid synthesis must be balanced by replenishment if the available pool is to remain steady. Thus the citric acid cycle connects energy metabolism to synthesis as well as to breakdown.^[ref]

The carbon sequence is oxaloacetate $(4)$ plus an acetyl group $(2)$ to citrate $(6)$, then isocitrate $(6)$, alpha-ketoglutarate $(5)$, succinyl-CoA $(4)$, succinate $(4)$, fumarate $(4)$, malate $(4)$ and back to oxaloacetate $(4)$. The numbers count the cycling carbon skeleton, excluding coenzyme A. Two carbon dioxide releases accompany the changes $6\to 5\to 4$.^[ref]

Per acetyl group: three NADH, one FADH2 equivalent, one GTP or ATP by substrate-level phosphorylation, and two carbon dioxide. Succinate dehydrogenase retains FADH2 and transfers its Electrons to ubiquinone, forming ubiquinol. The FADH2 equivalent and ubiquinol count the same Electron pair.^[ref]

A useful check adds the stepwise changes. The carbon count is $4+2-1-1=4$; the NADH count is $1+1+1=3$. Each NADH carries two Electrons, and the succinate dehydrogenase route supplies another pair, so one turn exports $3\times 2+2=8$ Electrons. This arithmetic is an accounting identity, not an ATP yield calculation. Converting it to ATP requires the separate energy coupling and transport assumptions discussed under oxidative phosphorylation.

For a chosen ideal conversion of $5\mu \mathrm{mol}$ of acetyl groups, multiplication gives $15\mu \mathrm{mol}$ of NADH, $5\mu \mathrm{mol}$ of ubiquinol, $5\mu \mathrm{mol}$ of GTP and $10\mu \mathrm{mol}$ of carbon dioxide. The Electron output is $40\mu \mathrm{mol}$. If all these Electrons subsequently reach oxygen with no competing sinks, four Electrons per oxygen molecule require $10\mu \mathrm{mol}$ of oxygen. That is consumption by the connected electron transport chain; it is not an oxygen term in the cycle's own substrate ledger.

No cycle step directly consumes molecular oxygen. In ordinary aerobic mitochondrial operation, however, the mitochondrial respiratory chain must reoxidize NADH and ubiquinol to restore the oxidized electron carriers. Without that outlet, a finite oxidized-carrier pool cannot sustain continued turnover. Other electron acceptors and other forms of metabolism require their own analysis.^[ref]

The pyruvate dehydrogenase complex acts upstream: one three-carbon pyruvate gives one two-carbon acetyl group, one carbon dioxide and one NADH. These are additional to the cycle ledger.^[ref] Consequently, processing one pyruvate through both stages gives three carbon dioxide and four NADH, while the succinate dehydrogenase contribution and the substrate-level phosphorylation contribution each remain one. Counting the upstream step inside the cycle would obscure where the extra carbon dioxide and NADH arise.