Pyruvate Oxidation A 0 1 2 3 A 9 04 04 9 8 9 43 04 01 2 3 Pyruvate OH NAD CoA SH 43 5 0 NADH CO2 9 04 Acetyl CoA O C O C O CH3 637 6 5 0 Pyruvate Dehydrogenase Complex CoA S C CH3 3 NAD FAD GDP Pi TCA Cycle CoA SH 3 NADH FADH2 GTP 2 CO2 Proteins in the Pyruvate Dehydrogenase Complex E1 Pyruvate dehydrogenase Pyruvate decarboxylase E2 Dihydrolipoyl acetyltransferase E3 Dihydrolipoyl dehydrogenase Protein X E1 kinase Phospho E1 phosphatase Eukaryotes gram positive prokaryotes Gram negative prokaryotes E coli Eukaryotic ribosome Prokaryotic ribosome Size megaDa E1 peptides E2 peptides E3 peptides 10 120 2 tetramers 60 trimers 24 dimers 4 6 24 24 12 4 2 4 RNA 6880 bases and 84 polypeptides 2 7 3 RNA 4860 bases and 57 polypeptides NH2 H N N N H3C S H3C S S H N Lipoamide E2 Thiamin pyrophosphate O Lys E2 O O O P O P O O O O O H3C N H3C NH N N O O N O P O P O CH2 O O OH OH O O P O N O N O P O CH2 O O Flavin adenine dinucleotide FAD N O P O O P O CH2 N O OH N OH N N O H3C C CH3 OH OH HO CH O C NH O H H2C CH2 C N CH2 CH2 SH O OH O CH2 N N O N OH NH2 O NH2 N N CH2 O OH HO NH2 NH2 OH Nicotinamide adenine dinucleotide NAD Coenzyme A CoA SH Pyruvate Dehydrogenase Complex H Pyruvate NH2 N H3C N N N O O H3 C R H3C R H3C CH3 C R S SH H N Acetyl Lipoamide E2 N H3C Lys E2 O O N S R OH C S S H N S R Lys E2 Lipoamide E2 O Hydroxyethyl TPP E1 CoA SH Acetyl CoA C C CO2 O O OH O TPP E1 O P O P O O C S H3C O C O R S H3C Thiamin pyrophosphate TPP E1 H3C H H O O CoA S C CH3 HS SH H N S Cys Lys E2 Dihydrolipoamide E2 O S Cys Oxidized E3 FAD SH SH Cys Cys Reduced E3 FAD NAD NADH S Cys CH3 Cu H AsO4 H3C As O As O Arsenite R SH SH Cl S As Lipoamide Organic Arsenical Cl As Cl Cys O CH3 Trimethylarsine R As O S S Lipoamide H2C SH HC SH H2C OH Oxidized E3 FAD Tricarboxylic Acid TCA Cycle O Acetyl CoA H3C C S CoA Oxaloacetate Malate O 8 OH O O O NAD O O 1 H2C HO O CoA SH NADH O O C O O 2 O O O H2O 2 O 5 Succinyl CoA Synthetase H2C 6 Succinate Dehydrogenase HO 7 Fumarase 8 Malate Dehydrogenase FAD O Succinate O C 4 Ketoglutarate Dehydrogenase FADH2 6 H2C O 2 Aconitase 3 Isocitrate Dehydrogenase O Fumarate O cis Aconitate O H2O O 1 Citrate Synthase O O O O 7 H2O Citrate O O O O O CoA SH 5 H2C C O NADH CoA H2C O NAD C CoA SH H2C O O O Succinyl CoA S O O Isocitrate 3 NADH GDP Pi O O O NAD GTP C 4 O CO2 O O Ketoglutarate C O O O Oxalosuccinate 3 CO2 O O O 5869 5869 05 9 056 7 4 4 4 31 2 03 4 0 1 4 4 056 7 3 4 2 05 9 4 32 2 03 0 1 2 0 1 05 9 0 1 056 7 AB E0 D E0 D 056 7 C0 D B Porcine Sus scrofa citrate synthase bound to citrate pdb ID 1CTS and to both citrate and CoA pdb ID 2CTS 4 2 0 1 2 012 34 5 1 5 6 47 1 0 1 2 78 945 78 945 3 4 5 6 9 1 0 1 2 34 5 17 67 8 012 678 012 34 5 4 3 4 Reaction Acetate combustion G kJ mol Typical G in cells kJ mol 849 TCA cycle 40 115 Citrate synthase 31 4 53 9 Aconitase 6 7 0 8 Isocitrate Dehydrogenase 8 4 17 5 ketoglutarate dehydrogenase 30 43 9 Succinyl CoA synthetase 3 3 0 Succinate dehydrogenase 0 4 0 Fumarase 3 8 0 Malate dehydrogenase 29 7 0 Anaplerotic reactions CO2 ATP O Pi ADP O C O C O C O C O Pyruvate carboxylase CH3 CH2 C O O Oxaloacetate Pyruvate NH2 ATP O HO C O O O O P O P O P O CH2 O O O O Carboxyphosphate N N ADP O P O O Pi O O C C CH2 H N O O O O OH Pyruvate O O O O NH C N NH Carboxybiotinyl enzyme O C O C C CH2 C O HO Enolpyruvate O O N N O H N S Biotin Lys Enzyme H N Lys Enzyme S O O O O O C O Oxaloacetate O C C CH2 O CH2 C O O NH 4 NAD CH2 C O NADH CH2 CH2 H3 N CH C O C O Glutamate C O Glutamate dehydrogenase O ketoglutarate O O Aspartate NH2 N O N O P O CH2 O O HO O CH2 C O O N HN NH4 N OH AMP deaminase Adenosine Monophosphate AMP O N O P O C H2 O O HO O C H2 C O O O C CH NH O C CH N N OH Inosine Monophosphate IMP NH3 GTP N GDP Adenylosuccinate synthetase O N O P O C H2 O O HO N AMP N O O CH C O OH Adenylosuccinate lyase Adenylosuccinate monophosphate O C CH Fumarate