TCA Cycle Biochem 4511 Figures Essential Biochemistry 3rd Ed Pratt and Cornely Principles of Biochemistry 5th Ed Moran et al Fundamentals of Biochemistry 2nd Ed Voet Voet and Pratt Overview of the Citric Acid Cycle In the citric acid cycle an acetyl group is condensed with oxaloacetate two CO2 are lost and oxaloacetate is regenerated Each round of the citric acid cycle generates three NADH one QH2 and one GTP ATP The TCA Cycle Malate Dehydrogenase In the malate dehydrogenase catalyzed reaction the final molecule of NADH is produced Go 29 7kJ mol The final product oxaloacetate can combine with acetyl CoA through the citrate synthase catalyzed reaction to restart the TCA cycle Regulation of the TCA Cycle Regulation of the TCA cycle occurs at the three irreversible steps Glyoxylate Cycle Biochem 4511 Figures Essential Biochemistry 3rd Ed Pratt and Cornely Principles of Biochemistry 5th Ed Moran et al Fundamentals of Biochemistry 2nd Ed Voet Voet and Pratt Glyoxylate Cycle Glyoxylate cycle allows some organisms primarily bacteria and plants to convert acetyl CoA into glucose Prohibited in humans An off shoot of the TCA cycle which proceeds without decarboxylation Two molecules of acetyl CoA consumed per turn to yield one molecule of oxaloacetate Requires two unique enzymes isocitrate lyase and malate synthase Acetyl CoA is the breakdown product from fatty acid degradation Generated oxaloacetate may be converted to glucose through gluconeogenesis Very low levels have been detected in some animals fetal rats Unique Reactions of the Glyoxylate Cycle Isocitrate Lyase Isocitrate Succinate Glyoxylate Malate Synthase CoA Glyoxylate Acetyl CoA Malate What is the net reaction of the glyoxylate cycle Which steps produce NADH NADH Which steps produce ubiquinol Which steps produce GTP ATP QH2 NADH The TCA Cycle is Not Always a Cycle Cataplerotic reactions deplete the components of the cycle Products are consumed in other pathways Anaplerotic reactions replenish the components of the cycle Products from other pathways are converted to substrates of the cycle TCA Cycle Can Be Rapidly Replenished Pyruvate from glycolysis can be converted to acetyl CoA AND oxaloacetate Pyruvate carboxylase the gluconeogenesis enzyme is activated by acetyl CoA If the energy charge is high lots of ATP oxaloacetate is converted into glucose If the energy charge is low little ATP oxaloacetate replenishes the citric acid cycle TCA Cycle Can Be Rapidly Replenished During exercise some pyruvate can be converted to ketoglutarate to boost the activity of the TCA cycle Many Amino Acids Interconvert with TCA Intermediates TCA cycle intermediates are precursors of other molecules Citrate Transport System Citrate and pyruvate cross the mitochondrial membrane via specific transport proteins Transport couples cytosolic metabolic pathways glycolysis with mitochondrial pathways TCA cycle This is the way to transport Acetyl CoA into cytosol for Amino Acid Biosynthesis from TCA Intermediates Total ATP Synthesis Potential of Glucose or x 1 NADH 2 5 ATP 1 QH2 1 5 ATP or xx ATP molecules Electrons transferred to NADH through glycolysis have two potential paths into the mitochondria which changes how many ATPs can be generated through electron transfer Net ATP yield of glucose catabolism xx or 32 depends on how electrons from cytoplasmic NADH are transported into the mitochondrial matrix 3 Phosphoglycerol Shuttle Muscle Malate Aspartate Shuttle Heart and Liver NADH FADH2 QH2 1 5 ATP NADH cyt NADH mit 2 5 ATP ATP Production The scheme on the right is another representation of total ATP production from glucose How many ATP can be generated from 1 Pyruvate 2 Acetyl CoA 3 ketoglutarate TCA Cycle Book Problems Problems 3 12 14 16 17 22 24 28 35 37 39 46 58 65 Need to know 1 5 steps of reactions by Pyruvate dehydrogenase 2 Enzymes cofactors reactants and products of each reaction in TCA cycle 3 Understand why TCA cycle is an energy generating 4 Understand anabolic and catabolic function of TCA cycle cycle 5 Understand the Glyoxylate Cycle