Learning path

Full curriculum

Full curriculum

Unit content

Citric-acid cycle as cyclic oxidation of acetyl groups

The citric-acid cycle—also called the tricarboxylic-acid (TCA) cycle or Krebs cycle—is a cyclic pathway that oxidizes the two-carbon acetyl group of acetyl-CoA while regenerating the molecule that accepts the next acetyl group.

In eukaryotic cells, most cycle reactions occur in the mitochondrial matrix.

A cycle regenerates its starting acceptor

Acetyl-CoA transfers its two-carbon acetyl group to the four-carbon compound oxaloacetate, producing the six-carbon compound citrate:

acetyl-CoA, 2 C + oxaloacetate, 4 C
                 ↓
              citrate, 6 C

A sequence of reactions then rearranges and oxidizes the carbon skeleton until four-carbon oxaloacetate is regenerated.

Because oxaloacetate is regenerated rather than consumed stoichiometrically, it can accept another acetyl group and begin another turn.

Carbon leaves as carbon dioxide

During one turn, two carbon atoms are released as two $\mathrm{CO_2}$ molecules.

The net carbon accounting is therefore

2-C acetyl group enters
2 CO2 leave
4-C oxaloacetate is regenerated

The individual carbon atoms released in the first turn need not be the exact two atoms that just entered as acetyl-CoA; carbon tracing through a cyclic pathway requires following atoms across multiple turns.

Most captured energy appears in reduced electron carriers

One turn of the cycle per acetyl-CoA typically produces

$$3\ \mathrm{NADH},$$

$$1\ \mathrm{FADH_2},$$

and one molecule of GTP or ATP by substrate-level phosphorylation, while releasing

$$2\ \mathrm{CO_2}.$$

GTP, guanosine triphosphate, is another nucleotide triphosphate. In cells it can be readily coupled to formation of ATP, so introductory energy accounting often counts one GTP as one ATP equivalent.

Because one glucose produces two acetyl-CoA molecules, two turns per glucose yield approximately

$$6\ \mathrm{NADH}+2\ \mathrm{FADH_2}+2\ \mathrm{ATP\ equivalents}+4\ \mathrm{CO_2}.$$

The cycle does not directly use oxygen

No step of the citric-acid cycle requires $\mathrm{O_2}$ as a direct reactant. Yet under aerobic respiration, the cycle depends indirectly on oxygen because NADH and FADH$_2$ must be reoxidized to regenerate NAD$^+$ and FAD.

If the oxidized carrier pools are not replenished, the redox steps of the cycle cannot continue at sustained flux.

The cycle is also a metabolic junction

Citric-acid-cycle intermediates can feed biosynthetic pathways, and other metabolic routes can replenish them. The cycle is therefore not merely a closed wheel whose only purpose is ATP production.

Its central bioenergetic role is to oxidize acetyl groups and transfer much of the released reducing power into NADH and FADH$_2$, which can then supply electrons to respiratory electron transport.