16 TCA and ETC Regulation Glucose tolerance and Insulin Resistance-1

16 TCA and ETC Regulation Glucose tolerance and Insulin Resistance-1

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TCA and ETC Regulation Glucose Tolerance Insulin Resistance HNFE 3025 Fall 2009
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TCA Cycle 3 Non-Equilibrium Reactions 2
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Regulation of the TCA Cycle Substrate regulation Acetyl CoA NAD + THINK…. .Where from-elec transport chain Regulation of three non-equilibrium reactions Citrate Synthase NADH is a negative allosteric effector WHY? Citrate is a competitive inhibitor for oxaloacetate Isocitrate DH NADH is a negative allosteric effector Ca 2+ is an activator Why do we continually find that calcium is important in regulating metabolism? α -Ketogluterate DH NADH is a negative allosteric effector Succinyl CoA is a competitive inhibitor for CoA Ca 2+ is an activator 3
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Regulation of the TCA Cycle To keep the TCA cycle functioning, oxaloacetate (need it to begin the TCA) and intermediates that can form oxaloacetate must be replenished Oxaloacetate, fumarate, succinyl-CoA, and - α ketoglutarate can all be formed from certain amino acids The single most important mechanism for ensuring ample oxaloacetate is the reaction from pyruvate via pyruvate carboxylase 4
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Pyruvate Carboxylase Important for gluconeogenesis(in liver) Acetyl-CoA (muscle) positively regulates pyruvate carboxylase Accelerating oxaloacetate formation with increasing levels of acetyl-CoA from sources other than glycolysis e.g., FFAs and AAs 5 Fig. 3-20, p. 89
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β α α γ Succinate:CoQ Oxidoreductase (Complex II) b Cyt c Cyt bc1 Cyt bc1 COX
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16 TCA and ETC Regulation Glucose tolerance and Insulin Resistance-1

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