lecture_23legge - 11/13/2009 Glycolysis III 11/10/09...

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11/13/2009 1 Glycolysis III 11/10/09 The metabolic fate of pyruvate The need to regenerate NAD + from NADH A. Homolactic fermentation: conversion of pyruvate to lactate O - O NH 2 O H R H S C O - O H NH 2 O H HO LDH Mammals have two different types of enzymes: Isozymes M type for muscle H type for heart CO CH 3 N + + H + R CH 3 N R + Pyruvate NADH L-Lactate NAD + Lactate dehydrogenase is a tetramer H4 has a low K m for pyruvate and is allosterically inhibited by high concentrations of pyruvate. M4 has a higher K m for pyruvate and is not allosterically regulated Although all five types can exist, H4, H3M, H2M2 HM3, M4 The M predominates in anaerobic muscle tissues which favor the formation of lactate while the H4 form predominates in aerobic tissues like heart where the formation of pyruvate from lactate is preferred Pro-R hydride is transferred from C4 of NADH to C2 of pyruvate with the concomitant transfer of a proton from His 195 All muscle lactate is transferred to the liver where it is turned back to glucose
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11/13/2009 2 Alcoholic fermentation A two step process: 1) Pyruvate decarboxylase requires thiamine pyrophosphate TPP as a cofactor. 2) Alcohol dehydrogenase requires Zn +2 as a cofactor Thiamine pyrophosphate The build up of negative charges seen in decarboxylation reactions on the carbonyl atom in the transition state is unstable and TPP helps stabilize the negative charge Reaction mechanism of pyruvate decarboxylation 1. Nucleophilic attack by the ylid from of TPP on the carbonyl 2. Departure of CO2 and resonance-
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This note was uploaded on 02/22/2011 for the course BCHS 3304 taught by Professor Johnson during the Spring '08 term at University of Houston.

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lecture_23legge - 11/13/2009 Glycolysis III 11/10/09...

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