Figure 16-1 Map of the major metabolic pathways in a typical cell.Figure 21-1 Reactions of the citric acid cycle.Slide 3Figure 21-6 The five reactions of the PDC.Figure 21-3a Electron micrographs of the E. coli pyruvate dehydrogenase multienzyme complex. (a) The intact complex. (b) The dihydrolipoyl transacetylase (E2) “core” complex.Figure 21-4 Structural organization of the E. coli PDC.Table 21-1 The Coenzymes and Prosthetic Groups of Pyruvate Dehydrogenase.Slide 8Figure 21-7 Interconversion of lipoamide and dihydrolipoamide.Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Figure 21-14 Catalytic reaction cycle of dihydrolipoyl dehydrogenase.Figure 21-16 The reaction transferring an electron pair from dihydrolipoyl dehydrogenase’s (E3) redox-active disulfide in its reduced form to the enzyme’s bound flavin ring.Figure 21-17a Factors controlling the activity of the PDC. (a) Product inhibition.Figure 21-17b Factors controlling the activity of the PDC. (b) Covalent modification in the eukaryotic complex.Slide 20Table 21-2 Standard Free Energy Changes (DG°¢) and Physiological Free Energy Changes (DG) of Citric Acid Cycle Reactions.Figure 21-18a Conformational changes in citrate synthase. (a) Space-filling drawing showing citrate synthase in the open conformation. (b) Space-filling drawing showing citrate synthase in the closed, substrate-binding conformation.Figure 21-19 Mechanism and stereochemistry of the citrate synthase reaction.Figure 21-20 Mechanism and stereochemistry of the aconitase reaction.Figure 21-21 Probable reaction mechanism of isocitrate dehydrogenase.Figure 21-22a Reactions catalyzed by succinyl-CoA synthetase. Formation of succinyl phosphate, a “high-energy” mixed anhydride.Figure 21-22b Reactions catalyzed by succinyl-CoA synthetase. Formation of phosphoryl–His, a “high-energy” intermediate.Slide 28Figure 21-23 Covalent attachment of FAD to a His residue of succinate dehydrogenase.Figure 21-24 Possible mechanisms for the hydration of fumarate as catalyzed by fumarase.Figure 21-25 Regulation of the citric acid cycle.Slide 32Figure 21-26 Amphibolic functions of the citric acid cycle.Figure 16-1 Map of the major metabolic pathways in a typical cell.Page 550Figure 21-1 Reactions of the citric acid cycle. Page 766AcetylCo A + 3 NAD+ + FAD + GDP + Pi2 CO2 + 3 NADH + FADH2 + GTP + CoATCA Cycle :Pyruvate + Coenzyme A + NAD+ Acetyl CoA + CO2 + NADHPyruvate Dehyrdogenase Reaction:Figure 21-6The five reactions of the PDC. Page 770Figure 21-3a Electron micrographs of the E. coli pyruvate dehydrogenase multienzyme complex. (a) The intact complex. (b) The dihydrolipoyl transacetylase (E2) “core” complex.Noncovalent assn. of prtoeins catalyzing sequential stepsFigure 21-4 Structural organization of the E. coli PDC.Page 769E2 Dihydrolypoly transacetlyase core(trimers)PDH: 24 Subunits (E1)(as dimers)24 subunits12 dihydrolypoyl dehydrogenase (E3)(as dimers)a+bEven more complex in yeast and mammals!Table 21-1 The Coenzymes and Prosthetic Groups of Pyruvate Dehydrogenase.Page 768Figure 21-2 Chemical structure of acetyl-CoA.G = -31.5 kJ/molFigure 21-7 Interconversion of lipoamide and dihydrolipoamide.Page 771Electron sink nature of TPP delocalizes the negative charge on the carbanion intermediateWhere have you seen this reaction before?Rxn 1: PyruvateDecarboxylase!Attack of carbanionon disulfide followedby TPP eliminationRxn 2: Transferof acetyl group toLipoamideRxn 3: Transfer of acetyl group to CoARxn 4:reoxidation of LARxn 5: E3 is reoxidezed by NAD+.Swings around among active sitesFigure 21-14 Catalytic reaction cycle of dihydrolipoyl dehydrogenase. Page 778Figure 21-16 The reaction transferring an electron pair from dihydrolipoyl dehydrogenase’s (E3) redox-active disulfide in its reduced form to the enzyme’s bound flavin ring. Page 780FAD acts like an electron conduit between reduced disulfide and NAD+.Figure 21-17a Factors controlling the activity of the PDC. (a) Product inhibition.Page 781Products drive the red reactions backwards!Figure 21-17b Factors controlling the activity of the PDC.(b) Covalent modification in the eukaryotic complex.Page 781Figure 21-1 Reactions of the citric acid cycle. Page 766Table 21-2 Standard Free Energy Changes (DG°¢) and Physiological Free Energy Changes (DG) of Citric Acid Cycle Reactions.Page 790Figure 21-18a Conformational changes in citrate synthase. (a) Space-filling drawing showing citrate synthase in the open conformation. (b) Space-filling drawing showing citrate synthase in the closed, substrate-binding conformation.Page 782Figure 21-19 Mechanism and stereochemistry of the citrate synthase reaction.Page 783Figure 21-20 Mechanism and stereochemistry of the aconitase reaction.Page 784Reversible rxnFigure 21-21 Probable reaction mechanism of isocitrate dehydrogenase.Page 785Mn+2or Mg+2Intermediate identified by site specific mutagenesis of active site to slow the rxn rateFigure 21-22a Reactions catalyzed by succinyl-CoA synthetase. Formation of succinyl phosphate, a “high-energy” mixed anhydride. Page 787succinateFigure 21-22b Reactions catalyzed by succinyl-CoA synthetase. Formation of phosphoryl–His, a “high-energy” intermediate.Page 787Succinate  Fumarate+ FAD + FADH2Enzyme?OO-HHOO__Inhibited byMalonateFumarate, malate or OAA  succinate in presence of malonateFigure 21-23 Covalent attachment of FAD to a His residue of succinate dehydrogenase.Figure 21-24 Possible mechanisms for the hydration of fumarate as catalyzed by fumarase.Page 788Figure 21-25 Regulation of the citric acid cycle.Page 791COO-CH3-+CoASH CH3C=OCoASHWhen in the TCA cycle would this label be lost as CO2?Figure 21-26 Amphibolic functions of the citric acid cycle.Page