Chapter20

Chapter20 - BCH 4054 Chapter 20 Lecture Notes Slide 1...

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Chapter 20, page 1 BCH 4054 Chapter 20 Lecture Notes Slide 1 Chapter 20 The Tricarboxylic Acid Cycle Slide 2 TCA Cycle aka Krebs Cycle and Citric Acid Cycle • Occurs inside mitochondria (the matrix) • Overall reaction: Acetyl-CoA + 3 NAD + + CoQ + GDP + P i 2 CO 2 + 3 NADH + CoQH 2 + GTP + CoASH • Bridging reaction required that converts pyruvate to acetyl-CoA. Mitochondria have two membranes: inner and outer. The outer has pores and is permeable to many things. The inner is a permeability barrier which requires specific transporters for most compounds to move across it. The matrix is inside the inner membrane. Slide 3 Bridging Reaction: Pyruvate Acetyl-CoA • Catalyzed by Pyruvate Dehydrogenase • Overall reaction: Pyruvate + CoASH + NAD + Acetyl-CoA + NADH + CO 2 • Two cosubstrate coenzymes: • Coenzyme A and NAD + • Three prosthetic group coenzymes: • thiamine pyrophosphate, lipoic acid, FAD The reaction is an oxidative decarboxylation of an alpha keto acid.
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Chapter 20, page 2 Slide 4 Pyruvate Dehydrogenase • Multienzyme complex (See Figure p.646) • Multiple copies of three enzymes, each with a prosthetic group: 12 subunits FAD DLD Dihydrolipoyl Dehydrogenase 24 subunits (cubic core) Lipoic Acid TA Dihydrolipoyl Transacetylase 24 dimers Thiamine Pyrophosphate PDH Pyruvate Dehydrogenase Note the first subunit has the same name as the overall enzyme. Slide 5 Pyruvate Dehydrogenase, con’t. • Mechanism involves two covalent intermediates with the enzyme: • Addition of pyruvate to TPP and loss of CO 2 forms hydroxyethyl TPP . • (This same intermediate is formed by pyruvate decarboxylase in yeast alcoholic fermentation). • Transfer of hydroxyethyl group to lipoic acid to form acetyl lipoic acid. • (This is an internal oxidation-reduction: acetaldehyde is oxidized, lipoic acid is reduced.) • See mechanisms page 646. Slide 6 Pyruvate Dehydrogenase, con’t. • Note the role of lipoic acid as a swinging arm that can move to bind to three different active sites. It cycles through three chemical forms. • The overall reaction is irreversible. • The enzyme is found inside the mitochondria. Therefore pyruvate must cross the mitochondrial membrane.
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Chapter 20, page 3 Slide 7 ABC’s of the TCA Cycle • A: two carbon unit (acetyl-CoA) is A dded to four carbon carrier (oxaloacetate) to form six carbon intermediate (citrate) • B: six carbon intermediate is B roken Down to four carbon succinate.
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This note was uploaded on 05/22/2011 for the course BCH 4054 taught by Professor Logan/gilmer during the Spring '06 term at FSU.

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Chapter20 - BCH 4054 Chapter 20 Lecture Notes Slide 1...

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