Tricarboxylic acid cycle

The cycle is also called Krebs' cycle, after Hans Krebs, who first worked it out, or the citric acid cycle. It runs in the mitochondrial matrix.

It starts when the acetyl group (2C) condenses with oxaloacetic acid (OAA, 4C) and water to give citric acid (6C). Citrate synthase catalyses this, and CoA is set free.

Citrate is isomerised to isocitrate. Two decarboxylations follow in succession, giving α-ketoglutaric acid (5C) and then succinyl-CoA; each releases one CO₂.

Succinyl-CoA is converted to succinic acid, making one GTP. This is substrate-level phosphorylation; in a coupled reaction the GTP becomes GDP as ADP becomes ATP.

The rest of the cycle oxidises succinic acid, via malic acid, back to OAA so the cycle can go on.

Each turn has three steps where NAD⁺ is reduced to NADH + H⁺ and one where FAD⁺ is reduced to FADH₂.

For the cycle to keep running, OAA must be continually replenished, and NAD⁺ and FAD⁺ must be regenerated from NADH and FADH₂.

Summary per pyruvic acid (matrix): pyruvic acid + 4NAD⁺ + FAD⁺ + 2H₂O + ADP + Pi → 3CO₂ + 4NADH + 4H⁺ + FADH₂ + ATP. This includes the link reaction.

Per glucose, counting the link reaction, the story so far is 8 NADH + H⁺, 2 FADH₂ and 2 ATP (from the cycle), with 6 CO₂ released. Neither O₂ nor the large ATP yield has appeared yet.