TCA Cycle (Krebs cycle or tricarboxylic acid)

The citric acid cycle (Krebs cycle or tricarboxylic acid) is the most important metabolic pathway for the energy supply to the body.
About 65-70% of the ATP is synthesized in Krebs cycle only.
Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O. Krebs cycle is the final common oxidative pathway for carbohydrates, fats or amino acids, through acetyl CoA.

1. TCA/Citric acid/Krebs Cycle Mr. S Maheen Abdul Rahman, M. Pharm. Assistant Professor Department of Pharmaceutical Chemistry PA College of Pharmacy (PACP) Mangalore, Karnataka.

2. TCA cycle The citric acid cycle ( Krebs cycle or tricarboxylic acid ) is the most important metabolic pathway for the energy supply to the body. About 65-70% of the ATP is synthesized in Krebs cycle only. Citric acid cycle essentially involves the oxidation of acetyl CoA to CO 2 and H 2 O. Krebs cycle is the final common oxidative pathway for carbohydrates, fats or amino acids , through acetyl CoA.

3. The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. This cycle not only supplies energy but also provides many intermediates required for the synthesis of amino acids, glucose, heme etc. The citric acid cycle was proposed by Hans Adolf Krebs in 1937, based on the studies of oxygen consumption in pigeon breast muscle. The cycle is named in his honor (Nobel Prize for Physiology and Medicine in 1953 .)

4. Reactions of TCA cycle Oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase complex This step is a connecting link between glycolysis and TCA cycle Formation of citrate Citrate is isomerized to isocitrate Isocitrate to oxalosuccinate Formation of a -ketoglutarate Conversion of a -ketoglutarate to succinyl CoA 6. Formation of succinate 7. Conversion of succinate to fumarate 8. Formation of malate 9. Conversion of malate to oxaloacetate

5. Total Number of ATP produced in TCA Cycle = 24 (2 NADH)

6. Summary of TCA Cycle: Acetyl CoA + 3 NAD+ + FAD + CDP + Pi + 2H2O 2CO2 + 3NADH + 3H+ + FADH2 + GTP + CoA Net ATP synthesis in glycolysis in aerobic condition 8 Pyruvate dehydrogenase (2 NADH, ETC, oxidative phosphorylation 6 Total ATP in TCA cycle 24 Total ATP per mole of glucose under aerobic condition 38

7. TCA cycle (enzyme-aconitase) is inhibited by fluorocitrate . The compound fluoroacetate, as such, is a harmless substrate. But it is converted to a toxic fluorocitrate by cellular metabolism. This is a suicide reaction committed by the cell, and thus fluoroacetate is regarded as a suicide substrate. Fluoroacetate- a suicide substrate : The inhibitor fluoroacetate is first activated to fluoro acetyl CoA which then condenses with oxaloacetate to form fluorocitrate.

8. Anaplerosis or anaplerotic reactions: The reactions concerned to replenish or to fill up the intermediates of citric acid cycle are called anaplerotic reactions or Anaplerosis.

9. REFERENCE BOOK: Textbook of biochemistry by Satyanarayana and chakrapani