CHM362H5 Lecture Notes - Lecture 23: Methylmalonyl-Coa, Epimerase And Racemase, Citric Acid Cycle

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2 Jan 2016
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Breakdown of odd-numbered fatty acids: odd-carbon fatty acids are metabolized by -oxidation. 3-c fragment - propionyl-coa: propionyl-coa is converted to succinyl-coa, succinyl-coa is a tca cycle intermediate. Reaction 1:to l-methylmalonyl coa: carboxylation at a-c of propionyl-coa. D-methylmalonyl coa: catalyzed by biotin-dependent enzyme, propionyl-coa carboxylase. Reaction 2: conversion of d-methylmalonyl coa to l-methylmalonyl. Reaction 3: methylmalonyl-coa mutase converts to l- methylmalonyl coa to succinyl-coa, vitamin b12-dependent. Methylmalonyl coa epimerase: epimerase reaction involves formation of a carbanion at a-c position, reversible dissociation of acidic a-h. Pka for -h is 21: if binding of h to -anion is diffusion limited, then -h dissociation is rate limiting. Koff = ka x kon = (10-21m)(10-9 m-1sec-1) = 10-12sec-1. Conversion of succinyl-coa to acetyl-coa: succinyl-coa derived from propionyl-coa can enter the tca cycle, but tca cycle intermediates are catalytic. Oxidation of mono-unsaturated fatty acids: oleic acid, palmitoleic acid, normal -oxidation for three cycles, cis- 3 acyl-coa cannot be utilized by acyl-coa dehydrogenase.

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