Tricarboxylic acid cycle (TCA Cycle) lect 11.pdf

Objectives At the end of this topic the students should be able to: 1. Describe further processing of acetyl in TCA cycle 2. Calculate the energy yield per turn of the cycle Prof S Nayak Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle] [Citric acid cycle] Is the final common oxidative pathway for...

Objectives At the end of this topic the students should be able to: 1. Describe further processing of acetyl in TCA cycle 2. Calculate the energy yield per turn of the cycle Prof S Nayak 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 Prof S Nayak Prof S Nayak 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 Prof S Nayak 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 Prof S Nayak 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 Prof S Nayak 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 Prof S Nayak }- 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, Dr S Nayak Prof S Nayak