8.5 : The Citric Acid Cycle

The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three NADH molecules, one FADH₂ molecule, and two CO₂ molecules.

Acetyl CoA is the point-of-entry into the citric acid cycle, which occurs in the inner membrane (i.e., matrix) of mitochondria in eukaryotic cells or the cytoplasm of prokaryotic cells. Prior to the citric acid cycle, pyruvate oxidation produced two acetyl CoA molecules per glucose molecule. Hence, the citric acid cycle runs twice per glucose molecule.

The citric acid cycle can be partitioned into eight steps, each yielding different molecules (italicized below).

With the help of catalyzing enzymes, one acetyl CoA (2-carbon) reacts with oxaloacetic acid (4-carbon), forming the 6-carbon molecule citrate.

Next, citrate is converted into one of its isomers, isocitrate, through a two-part process in which water is removed and added.

The third step yields α-ketoglutarate (5-carbon) from oxidized isocitrate. This process releases CO₂ and reduces NAD⁺ to NADH.

The fourth step forms the unstable compound succinyl CoA from α-ketoglutarate, a process that also releases CO₂ and reduces NAD⁺ to NADH.

The fifth step produces succinate (4-carbon) after a phosphate group replaces the CoA group of succinyl CoA. This phosphate group is passed on to ADP (or GDP) to form ATP (or GTP).

The sixth step forms fumarate (4-carbon) from the oxidation of succinate. This reaction reduces FAD to FADH₂.

The seventh step, in which water is added to fumarate, generates malate (4-carbon).

The final step produces oxaloacetate, the compound that reacts with acetyl CoA in step one, from the oxidation of malate. In the process, NAD⁺ is reduced to NADH.

The NADH and FADH₂ produced in the citric acid cycle provide electrons in the electron transport chain and, hence, aid the production of additional ATP.