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Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle] [Citric acid cycle]

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

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Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle] [Citric acid cycle]

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  1. 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 • Twocarbon, acetyl CoA + 4 carbon, Oxaloacetate = 6 carbon tricarboxylic acid, citrate

  2. 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

  3. 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

  4. Amphibolic nature of TCA cycle Non essential aa Aspartate Acetyl CoA Purines , Transamination Pyrimidines. Oxaloacetate Citrate Acetyl CoA Fatty acids, steroids Pyruvate Malate  -KG Transanimation Succinyl COA Glutamate Heme Non-essential a a, purines

  5. 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

  6. Regulation of TCA cycle • 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

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