Methylmalonyl CoA racemase

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... 

Figure 28-7. The metabolism of branched-chain amino acids and odd-chain fatty acids via propionyl-CoA. Propionyl-CoA is converted to D-methylmalonyl-CoA by propionyl-CoA carboxylase. D,L-Methylmalonyl-CoA racemase catalyzes the conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA. L-methyl malonyl-CoA mutase, an adenosyicobalamin-requiring enzyme, converts L-methylmalonyl-CoA to succinyl-CoA.TCA cycle is citric acid cycle or Kreb s cycle.

Methylmalonic aciduria, Type I methylmalonyl CoA mutase deficiency Type II 5 -deoxyadenosylcabolamin deficiency Type IV methylmalonyl CoA racemase deficiency... 

Methylmalonyl-CoA racemase converts D-methylmalonyl-CoA to the L-isomer by labilization of an a-hydrogen atom, followed by uptake of a proton from the medium. 

In the first step, propionyl-CoA is carboxylated by propionyl-CoA carboxylase, an enzyme with a biotin cofactor. The product, L-methylmalonyl-CoA, is isomerized by methylmalonyl-CoA racemase to form D-methylmalonyl-CoA. In the last step, a hydrogen atom and the carbonyl-CoA group exchange positions. This unusual reaction is catalyzed by methylmalonyl-CoA mutase, an enzyme that requires vitamin B12. (Vitamin B12 is 5 deoxyadenosylcobalamin.)... 

R)-Methylmalonyl CoA mutase (coenzyme Bi2"d P dent), methylmalonyl CoA racemase ... 

Methylmalonyl-CoA racemase. The enzyme catalyzes the transformation of the isomer (b) of methylmalonyl-CoA to the isomer (a), which can be used at subsequent steps of propionic acid fermentation ... 

Fermentation of glucose, glycerol, and lactic acid by propionibacteria utilizing the succinate-propionate pathway. 1 (S)-methylmalonyl-CoA-pyruvate transcarboxylase, 2 malate dehydrogenase 3 fumarase, 4 fumarate reductase, 5 CoA transferase, 6 (R)-methylmalonyl-CoA mutase, and 7 methylmalonyl-CoA racemase... 

The final unique stage in the metabolism of L-isoleucine involves the cleavage of 2-methylacetoacetyl-CoA to acetyl-CoA and propionyl-CoA (Section 10.4). The propionyl-CoA is further metabolized to methylmalonyl-CoA by a biotin-dependent carboxylase and subsequently via succinyl-CoA into the tricarboxylic acid cycle. L-Valine is also metabolized ultimately to methylmalonyl-CoA (Section 10.4), and thus these two branched-chain amino acids form the major precursors of propionyl-CoA and methylmalonyl-CoA. Other precursors of propionyl-CoA include methionine, threonine, odd-carbon-number fatty acids and cholesterol. The methyhnalonyl-CoA produced by propionyl-CoA carboxylase occurs as the D(5)-enantiomer and is racemized to the L(/ )-enantiomer by methylmalonyl-CoA racemase. l(/ )-Methylmalonyl-CoA is then metabolized to succinyl-CoA by a vitamin B12-dependent mutase prior to introduction of the modified molecule into the tricarboxylic acid cycle. 

Carboxylation of propionyl-CoA leads to the formation of D(5)-methyl-malonyl-CoA. D-Methylmalonyl-CoA is converted by methylmalonyl-CoA racemase (EC 5.1.99.1) into the L(/ )-isomer which is in turn converted into succinyl-CoA by the vitamin B 12-dependent methylmalonyl-CoA mutase (EC 5.4.99.2) (formerly isomerase), the succinyl-CoA subsequently entering the tricarboxylic acid cycle. 

Methylmalonyl-CoA racemase deficiency McKusick (1978) 25112, type III Chalmers etal. (1980) type IV... 

Mazumder, R., Sasakawa, T., Kaziro, Y. and Ochoa, S. (1962), Metabolism of propionic acid in animal tissues. IX. Methylmalonyl CoA racemase. J. Biol. Chem., 372, 3065. 

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