Citric acid cycle: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Citrate, alpha-ketoglutarate, succinate, fumarate, malate: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

The citric acid cycle is a chain of enzyme steps in the mitochondrion that forms citrate, alpha-ketoglutarate, succinate, fumarate and malate. It breaks acetyl-CoA down to CO₂ and loads electron carriers for the respiratory chain.

The pathway step by step

1. Pyruvate → Acetyl-CoA PDH complex · Vitamin B1 (TPP), Lipoic acid The pyruvate dehydrogenase complex removes one carbon atom as CO₂ and transfers the rest to coenzyme A. It needs thiamine (vitamin B1) and lipoic acid. Source 3
2. Acetyl-CoA → Citrate Citrate synthase · Oxaloacetate Citrate synthase joins acetyl-CoA with oxaloacetate to form citrate. With six carbon atoms, it is the largest station of the cycle. Source 1
3. Citrate → Isocitrate Aconitase · Iron-sulphur cluster Aconitase shifts an OH group within the molecule. This produces isocitrate, which is easier to convert in the next step. Source 1
4. Isocitrate → Alpha-ketoglutarate Isocitrate DH · NAD⁺ Isocitrate dehydrogenase splits off CO₂ and loads NAD⁺ to NADH. Alpha-ketoglutarate is also the starting material for the amino acid glutamate. Source 1, 2
5. Alpha-ketoglutarate → Succinyl-CoA α-KG dehydrogenase · Vitamin B1 (TPP), NAD⁺ A second enzyme complex splits off CO₂ again; it also works with thiamine. Succinyl-CoA is, in addition, a building block for the red blood pigment. Source 1
6. Succinyl-CoA → Succinate Succinate thiokinase · GDP Releasing the bond to coenzyme A frees energy; the cell first stores it as GTP. Succinate remains. Source 1
7. Succinate → Fumarate Succinate DH · FAD Succinate dehydrogenase is also part of the respiratory chain. It removes two hydrogen atoms and transfers them to FAD. Source 1
8. Fumarate → Malate Fumarase · Water Fumarase adds a water molecule across the double bond. This produces malate. Source 1
9. Malate → Oxaloacetate Malate DH · NAD⁺ Malate dehydrogenase loads NAD⁺ to NADH once more. The resulting oxaloacetate picks up the next acetyl-CoA – and the cycle starts again. Source 1

Cofactors in this pathway

• Vitamin B1 (thiamine) — As thiamine pyrophosphate, cofactor of the PDH complex and alpha-ketoglutarate dehydrogenase Source 3, 1
• NAD⁺ — Accepts electrons at three steps of the cycle and becomes NADH in the process Source 1In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Vitamin B2 (FAD) — As FAD, electron carrier of succinate dehydrogenase and the dehydrogenase complexes Source 1, 3
• Coenzyme A — Carries the acetyl and succinyl groups between the enzymes of the cycle Source 1, 3
• Lipoic acid — Cofactor in the PDH complex and in alpha-ketoglutarate dehydrogenase Source 3
• Iron — Part of the iron-sulphur centres of aconitase and succinate dehydrogenase Source 1In the ORY catalogue as a laboratory value: Eisen
• Magnesium — Binds thiamine pyrophosphate in the active site of the PDH complex Source 3In the ORY catalogue as a laboratory value: Magnesium

Sources

1. Arnold PK, Finley LWS. Regulation and function of the mammalian tricarboxylic acid cycle. J Biol Chem 2023 · PubMed 36581208
2. Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 2020 · PubMed 31900386
3. Patel MS, Nemeria NS, Furey W et al. The pyruvate dehydrogenase complexes: structure-based function and regulation. J Biol Chem 2014 · PubMed 24798336

Related pathways

• Branched-chain amino acids — succinyl-coa
• GABA, glutamate and glutamine — succinate
• Lactate and pyruvate — oxaloacetate
• Threonine — succinyl-coa
• Vitamin B12 — succinyl-coa

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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