17-TCAcycle - 1 Berg • Tymoczko • Stryer Biochemistry...

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Unformatted text preview: 1 Berg • Tymoczko • Stryer Biochemistry Sixth Edition Chapter 17: The Citric Acid Cycle Copyright © 2007 by W. H. Freeman and Company The Citric Acid Cycle • Glycolysis produces just 2 ATP molecules • Aerobic metabolism of glucose → CO 2 gives more ATP • Main part called the citric acid cycle - Tricarboxylic acid (TCA) cycle cycle - Krebs cycle - 2 The Citric Acid Cycle • Pyruvate must be converted to acetyl-CoA • Pyruvate + coenzyme A + NAD + → acetyl-CoA + CO + NADH CO 2 + NADH • Acetyl-CoA then enters the citric acid cycle, which occurs inside mitochondria The Citric Acid Cycle • Citric acid cycle the "metabolic hub" of the cell 6 carbon tricarboxylic acid cell - Fuels aerobically oxidized - A source of precursors for amino acids nucleotide acids, nucleotide bases, porphyrin - 3 The Citric Acid Cycle • How does the citric acid cycle connect to other metabolic pathways? The Citric Acid Cycle • Pyruvate + coenzyme A + NAD + → acetyl-CoA + CO 2 + NADH - Pyruvate transported through membrane protein - Pyruvate transported through membrane protein into mitochondria - Pyruvate dehydrogenase complex catalyzes this irreversible reaction • Complex of 3 enzymes • Member of a large family with masses from 4 million to Member of a large family, with masses from 4 million to 10 million daltons • 4 The Citric Acid Cycle The Citric Acid Cycle 5 Mechanism of Pyruvate → Acetyl CoA • Pyruvate + CoA + NAD + → Acetyl CoA + CO 2 + NADH + H + - Requires 5 coenzymes • Catalytic cofactors: thiamine pyrophosphate (TPP), lipoic acid, and FAD FAD • Stoichiometric cofactors: CoA and NAD+ - Mechanism of Pyruvate → Acetyl CoA 6 Mechanism of Pyruvate → Acetyl CoA • Decarboxylation - Catalyzed by E 1 of pyruvate dehydrogenase complex complex Mechanism of Pyruvate → Acetyl CoA • Oxidation - Catalyzed by the pyruvate dehydrogenase component of the dehydrogenase component of the complex (E 1 ) - 7 Mechanism of Pyruvate → Acetyl CoA • Transfer to CoA - Catalyzed by dihydrolipoyl transacetylase (E 2 ) Thioester bond remains in produc - Thioester bond remains in product - Mechanism of Pyruvate → Acetyl CoA • Step 4: Dihydrolipoamide oxidized to lipoamide - Catalyzed by dihydrolipoyl dehydrogenase (E 3 ) 2 e transferred to FAD then to NAD + - 2 e- transferred to FAD then to NAD + - - 8 Mechanism of Pyruvate → Acetyl CoA • Complex structure of the complex 12 E 3 ( αβ ) N-terminus 24 E 1 ( α 2 β 2 ) 8 E 2 ( α 3 ) Mechanism of Pyruvate → Acetyl CoA • Advantages of a compact multienzyme complex...
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17-TCAcycle - 1 Berg • Tymoczko • Stryer Biochemistry...

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