Lecture 17 Chapters 18 19 The Tricarboxylic Acid Cycle TCA a k a Kreb s cycle a k a Citric Acid Cycle CAC 1 Outline Overview of the process of complete oxidation of glucose glycolysis TCA Cycle Oxidative Phophorylation Preparatory step for TCA Cycle Pyruvate Acetyl CoA Reactions of the TCA Cycle 8 Regulation of the TCA Cycle TCA Cycle can also provide precursors for biosynthesis Anaplerotic reactions The glycoxylate cycle 2 1x 2x 2x 2x NADH 2x 2x 2x GTP Oxidative phosphorylation 2x 3 NADH 1 FADH2 3 4 The Decisive Step The Pyruvate Dehydrogenase Complex Pyruvate CoA NAD Acetyl CoA CO2 NADH H pyruvate 5 Preparation for the cycle The point of no return 6 7 Pyruvate Dehydrogenase Complex uses three Catalytic Coenzymes Prosthetic groups Thiamine pyrophosphate E1 TPP Thiazole ring E2 Lipoic acid E3 FAD 8 Lipoic Acid Lysine Lipoamide 9 Pyruvate Dehydrogenase Complex uses two Stoichiometric Coenzymes Coenzyme A mercaptoethalamine Bound to acetyl group Pantothenic acid NAD ATP 10 PDH Catalytic and Stoichiometric Coenzymes NAD E1 E3 CoA lipoamide E2 E2 11 The synthesis of acetyl CoA from pyruvate consists of three steps 1 2 3 12 Step 1 Decarboxylation E1 13 Step 2 Oxidation E1 Acetyl group is oxidized and transferred to one of lipoamide S The other S of lipoamide is reduced 14 Step 3 Formation of acetyl CoA E2 15 4 Reoxidation of dihydrolipoamide E3 16 5 Transfer of electrons to NAD E3 17 Flexible Linkages Allows Lipoamide to move between Active Sites http iai asm org content 28 3 to 18 Regulation of the PDH Complex Low blood glucose High energy charge High blood glucose Low energy charge 19 Allosteric Regulation of E2 and E3 Pyruvate CoA NAD Substrates Pyruvate dehydrogenase Acetyl CoA NADH Products E1 Pyruvate E2 NAD E3 Acetyl CoA NADH ATP 20 The Covalent Regulation of the Pyruvate Dehydrogenase Component E1 in Higher Eukaryotes E1 E1 21 active ATP inactive ADP Pyruvate dehydrogenase Pyruvate dehydrogenase P E1 E1 E2 Pyruvate dehydrogenase kinase Pyruvate dehydrogenase phosphatase E3 E2 E3 Pi H2 O 22 NAD HS CoA ADP Pyruvate active ATP High energy stimulates kinase NADH Acetyl CoA inactive ADP Pyruvate dehydrogenase Pyruvate dehydrogenase P E1 E1 E2 Pyruvate dehydrogenase kinase Pyruvate dehydrogenase phosphatase E3 insulin liver and adipose epinephrine E2 E3 Pi H2 O NAD Ca2 and HS CoA Low energy stimulates phosphatase 23 Advantages of Multienzyme Complexes Can pass substrate intermediate quickly and efficiently faster reaction and less side product Component assembled in best stoichiometry 24 The TCA cycle 3 NADH 1 FADH2 25 Two Phases of TCA Phase 1 Phase 2 26 TCA Reactions TCA provide a chemically feasible way of cleaving a two carbon compound CH3COO CO2 CO2 Reaction 1 Condensation 2 4 6 Reaction 2 Dehydration Rehydration First Stage Reaction 3 Decarboxylation Reaction 4 Decarboxylation Reaction 5 Substrate level Phosphorylation Reaction 6 Oxidation Second Stage Reaction 7 Hydration Reaction 8 Oxidation 27 Citrate Synthase forms citrate from oxaloacetate and acetyl coenzyme A Error in p 332 of textbook Used citrate instead of OAA G 31 4 kJ mol G 53 9 kJ mol 28 The mechanism of citrate synthase prevents undesirable reactions 29 Reaction 2 Citrate is isomerized into isocitrate Aconitase G 6 7 kJ mol 30 TCA Cycle Steps 3 4 Elimination of 2 Cs from Acetyl CoA 31 3 Isocitrate is oxidized and decarboxylated to ketoglutarate Isocitrate Dehydrogenase G 8 4 kJ mol G 17 5 kJ mol 32 Step 4 Succinyl CoA is formed by the oxidative decarboxylation of ketoglutarate ketoglutarate dehydrogenase complex G 30 kJ mol G 43 9 kJ mol 33 TCA Cycle Steps 5 8 Regeneration of Oxaloacetate and Harvest of Energy Rich Electrons 34 Reaction 5 Succinyl CoA to Succinate Succinyl CoA synthetase G 3 3 kJ mol G 0 35 Substrate level Phosphorylation by Succinyl CoA Synthetase Succinyl CoA Succinate Succinyl phosphate 1 2 Succinyl CoA synthetase ADP GDP ATP GTP phosphohistidine 3 http en wikipedia org wiki File Succinyl CoA Synthetase Mechanism Revised png 4 36 Oxaloacetate is regenerated Reactions 6 8 Succinate Dehydrogenase fumarase Malate dehydrogenase 37 The Net Reaction of the Citric Acid Cycle is 38 Fatty acid breakdown Regulation of the TCA Cycle Fatty acid synthesis Isocitrate Dehydrogenase KG Dehydrogenase 39 Learn regulated enzymes in each pathways Substrate Product Allosteric effector Posttranscriptional modifications Learn the products ATP NADH CO2 etc of each pathway and the steps at which they are generated 40 The Citric Acid Cycle is a Source of Biosynthetic Precursors 41 Anaplerotic filling up reactions 42 Two phases of TCA Phase 1 Phase 2 43 The glycoxylate cycle enables plants and bacteria to convert fats into carbohydrates 44 The Glycoxylate Cycle 45 Complete Oxidation of glucose The electrons from glucose oxidation feed into the electron transport pathway driving synthesis of ATP In mitochondiral matrix 46 Learning Goals Be able to list the coenzymes of the pyruvate dehydrogenase and the steps involved in the conversion of pyruvate to acetyl CoA Be able to recognize the intermediates and products of the citric acid cycle Understand how the pyruvate dehydrogenase complex and the citric acid cycle are regulated Know the roles of acetyl CoA and oxaloacetate Explain the differences between the citric acid cycle and the glyoxylate cycle 47
View Full Document
Unlocking...