Tricarboxylic acid cycle TCA Cycle Krebs cycle Citric
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 v Site: mitochondrial matrix v Oxidation of acetyl Co. A Co 2 + H 2 O v Occurs in a cyclic manner, generate ATP v Two carbon, acetyl Co. A + 4 carbon, Oxaloacetate = 6 carbon tricarboxylic acid, citrate
Cis-aconitate is a transient one with very short half-life. Immediate H 2 O added to it and forms Isocitrate CO 2 · 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 FADH 2 = 2 ATP] 2 ATP x 1 = 2 ATP Step 7 1 GTP = 1 ATP x 1 = 1 ATP Therefore 1 acetyl Co. A gives 12 ATP Two acetyl Co. A 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 Co. A by TCA cycle 24 ATP Net Gain = 38 ATP
Amphibolic nature of TCA cycle Non essential aa Aspartate Acetyl Co. A Purines , Transamination Pyrimidines. Oxaloacetate Citrate Acetyl Co. A 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 +CO 2 + ATP carboxylase oxaloacetate + ADP + Pi Pyruvate +CO 2 + NADPH + Malic enzyme Malate Inhibitors that inhibit the enzymes of TCA cycle are: Aconitase fluoroacetate a- Ketoglutarate DH Arsenite Non-competitive Succinate DH Malonate }- competitive
Regulation of TCA cycle 1. Citrate synthase: inhibited by ATP, NADH, acyl Co. A and succinyl Co. A 2. Isocitrate dehydrogenase: Inhibited by ATP and NADH and activated by ADP 3. -KG dehydrogenase inhibited by NADH & succinyl Co. A The availability of ADP: Important for proceeding the TCA cycle if not oxidation of NADH and FADH 2 through election transport chain stops. Accumulation of NADH and FADH 2, inhibit the enzymes of TCA cycle. Ref: Essentials of Biochemistry/Handbook of Biochemistry
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