Citric acid cycle

Last updated: August 15, 2022

Summarytoggle arrow icon

The citric acid cycle (TCA cycle; also known as the Krebs cycle) is an essential metabolic pathway at the end of the degradation of all nutrients that yield acetyl-CoA, including carbohydrates, lipids, ketogenic amino acids, and alcohol. Acetyl-CoA is a product of glycolysis (at high glucose levels) or beta-oxidation (at low glucose levels) and the first substrate of the TCA cycle. Over the course of the cycle, acetyl-CoA is oxidized to CO2 in 8 steps, and the energy that this generates is stored in FADH2, NADH+H+, and GTP. FADH2, NADH+H+ are then oxidized in the mitochondrial respiratory chain (electron transport chain), which ends in ATP synthesis. The intermediates of the TCA cycle are precursors for both anabolic and catabolic processes.

Overviewtoggle arrow icon



Citrate Is Krebs' Starting Substrate For Making Oxaloacetate

Each C2 unit is completely oxidized to CO2 and H2O. Oxaloacetate is recycled for the next TCA cycle.


Under anaerobic conditions, the TCA cycle is inhibited because the electron transport chain cannot regenerate NADH+H+ and FADH2!

Processtoggle arrow icon

TCA cycle reactions and enzymes
Enzyme Substrate Product Regulation
Citrate synthase (irreversible)
  • Inhibited by ATP


  • -
Isocitrate dehydrogenase (irreversible)

α-Ketoglutarate dehydrogenase (irreversible)

  • α-Ketoglutarate (5C)
Succinyl-CoA synthetase
  • -
Succinate dehydrogenase
  • -
Malate dehydrogenase
  • -

Anaplerotic reactions

Amphibolic centertoggle arrow icon

The TCA cycle provides precursors for both anabolic and catabolic processes.

Summary of TCA-related amphibolic processes

Metabolic pathway of

Anabolic precursor Catabolic precursor
Amino acids
Fatty acids
  • -

Clinical significancetoggle arrow icon

Referencestoggle arrow icon

  1. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. McGraw-Hill Medical ; 2017
  2. Kaplan. USMLE Step 1 Lecture Notes 2018: Biochemistry and Medical Genetics. Kaplan ; 2017
  3. Chatterjea M, Shinde R. Textbook of Medical Biochemistry. JP Medical Ltd ; 2011

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 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer