Lecture 05

Lecture 05 - Lecture 5 Citric Acid Cycle (Krebs Cycle) 1...

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1 Lecture 5 Citric Acid Cycle (Krebs Cycle)
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2 Hans Krebs 1900-1981 Nobel Prize in Physiology or Medicine, 1953
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3 Glycolysis Glucose (6 carbons) converted to two molecules of pyruvate (3 carbons) And then two molecules of Acetyl-CoA (2 carbons)
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4 Everything feeds into the citric acid cycle What comes out? Energy NADH = (2.5 ATP) FADH 2 = (1.5 ATP) GTP = (ATP) 2 Carbons 2 Carbons Takes place in mitochondrion
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5 Coenzyme A (CoA) Derived from Vitamin B 5 High-energy thioester bond to acyl or acetyl groups
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6 Acetyl-Coenzyme A (Acetyl-CoA) Derived from Vitamin B 5 High-energy thioester bond to acyl or acetyl groups CH 3 —C ~ O
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7 Overview of the Citric Acid Cycle Acetyl group oxidative decarboxylation oxidative decarboxylation Regenerate oxaloacetate 8 electrons transferred to NAD + and FAD => 9 ATP
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8 Citric Acid Cycle and oxidative phosphorylation generate 90% of the energy
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9 What happens to pyruvate? Complete oxidation (aerobic) Muscles (anaerobic) Yeast (anaerobic) Pyruvate Dehydrogenase Pyruvate Decarboxylase Lactate Dehydrogenase
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10 Pyruvate dehydrogenase complex coverts pyruvate to acetyl-coA Pyruvate + CoA + NAD + -> acetyl-CoA + CO 2 + NADH + H + Link between glycolysis and citric acid cycle
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11 Pyruvate dehydrogenase complex is a large and integrated complex
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12 covert pyruvate to acetyl-coA Co-factors: TPP, lipoic acid, FAD CoA, NAD + Forms carbanion (C - )
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13 Mechanism: decarboxylation E 1
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14 Mechanism: decarboxylation Electron sink Acidic, pk a =10
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15 Mechanism: oxidation Hydroxyethyl group gets oxidized Form a high energy thioester bond E 1 E 2
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16 Mechanism: formation of acetyl CoA E 2 The high energy thioester bond is preserved
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17 Mechanism: oxidize dihydrolipoamide to lipoamide Two electrons transferred to FAD then to NAD + E 3
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18 Lipoamide cofactor Cyclic disulfide Oxidized Reduced Disulfide bond Inhibited by Arsenic
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19
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20 Structure of the complex 8 E2 trimer 24 E1 tetramer 12 E3 dimer
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Lecture 05 - Lecture 5 Citric Acid Cycle (Krebs Cycle) 1...

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