Citric acid cycle


The citric acid 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 citric acid 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 citric acid cycle are precursors for both anabolic and catabolic processes.




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!


Acetyl-CoA + oxaloacetatecitrateisocitrateα-ketoglutaratesuccinyl-CoAsuccinatefumaratemalateoxaloacetate

Enzyme Substrate Product Regulation
Citrate synthase (irreversible)
  • Inhibited by ATP


  • -
Isocitrate dehydrogenase (irreversible)
  • α-Ketoglutarate
  • CO2
  • Inhibited by ATP and NADH inhibit
  • Stimulated by ADP and Ca2+ stimulate

α-Ketoglutarate dehydrogenase (irreversible)

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

Anaplerotic reactions

Amphibolic center

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

Metabolic pathway of

Anabolic precursor Catabolic precursor
Amino acids
Fatty acids
  • -

Clinical significance

  • Chatterjea M, Shinde R. Textbook of Medical Biochemistry. New Delhi, India: JP Medical Ltd; 2011.
  • Kaplan. USMLE Step 1 Lecture Notes 2018: Biochemistry and Medical Genetics. New York, NY: Kaplan; 2017.
  • Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
last updated 11/22/2018
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