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Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle] [Citric acid cycle] Is the final common oxidative pathway for carbohydrates, fats and amino acids Along with energy, cycle supplies many intermediates required for the synthesis of amino acids, glucose, heme etc Site: mitochondrial matrix Oxidation of acetyl CoA Co2 + H2O Occurs in a cyclic manner, generate ATP Two carbon, acetyl CoA + 4 carbon, Oxaloacetate = 6 carbon tricarboxylic acid, citrate Cis-aconitate is a transient one with very short half-life. Immediate H2O added to it and forms Isocitrate CO2 Isocitrate oxalosuccinate -ketoglutatrate. It is an oxidative decarboxylation Oxalosuccinate is unstable so it undergoes spontaneous decarboxylation to from -KG TCA is both catabolic and anabolic amphibolic Energetics of TCA Cycle Steps 4, 6, 10 3 NADH 1 NADH = 3 ATP] 3 ATP x 3 = 9 ATP Step 8 1 FADH2 1 FADH2 = 2 ATP] 2 ATP x 1 = 2 ATP Step 7 1 GTP 1 GTP = 1 ATP 1 ATP x 1 = 1 ATP Therefore 1 acetyl CoA gives 12 ATP Therefore 1 acetyl CoA gives 12 ATP Two acetyl CoA in citric acid cycle produces 24 ATP Energetics of complete oxidation of glucose Aerobic glycolysis 8 ATP Oxidation of 2 pyruvate = 6 ATP Oxidation of 2 Acetyl CoA by TCA cycle 24 ATP Net Gain = 38 ATP Amphibolic nature of TCA cycle Non essential aa Aspartate Acetyl CoA Purines , Transamination Pyrimidines. Oxaloacetate Citrate Acetyl CoA Fatty acids, steroids Pyruvate -KG Transanimation Succinyl COA Glutamate Malate Heme Non-essential a a, purines Anaplerosis The reactions concerned to replenish the intermediates of TCA cycle are called anaplerotic reactions or anaplerosis Pyruvate +CO2 + ATP carboxylase oxaloacetate + ADP + Pi Pyruvate +CO2 + NADPH + H + Malic enzyme Malate Inhibitors that inhibit the enzymes of TCA cycle are: Aconitase fluoroacetate - Ketoglutarate DH Arsenite Non-competitive Succinate DH Malonate }- competitive Regulation of TCA cycle 1. Citrate synthase: inhibited by ATP, NADH, acyl CoA and succinyl CoA 2. Isocitrate dehydrogenase: Inhibited by ATP and NADH and activated by ADP 3. -KG dehydrogenase inhibited by NADH & succinyl CoA The availability of ADP: Important for proceeding the TCA cycle if not oxidation of NADH and FADH2 through election transport chain stops. Accumulation of NADH and FADH2, inhibit the enzymes of TCA cycle. Ref: Essentials of Biochemistry/Handbook of Biochemistry