Methyl malonyl-coA-mutase

Free radical reactions Once thought to be rare, the homolytic cleavage of covalent bonds to generate free radicals has now been found in a range of biochemical processes. Some examples are the reactions of methyl-malonyl-CoA mutase (see Box 17-2), ribonucleotide reductase (see Fig. 22-41), and DNA photolyase (see Fig. 25-25). 

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.

Mancia, F., and Evans, P. R., 1998, Conformational changes on substrate binding to methyl-malonyl CoA mutase and new insights into the free radical mechanism. Structure 6 7119720. 

The 5-deoxyadenosyl cobalamin and methyl cobalamin function as coenzyme forms and are required for the action of several enzymes. Methyl malonyl CoA mutase uses 5-deoxyadenosyl cobalamin as coenzyme. Methyl cobalamin functions as a carrier of methyl group to homocysteine and convert it to methionine... 

The related cobalt cofactor vitamin B12 (8), the coenzyme of methyl-malonyl CoA mutase and homocysteine transmethylase, contains a... 

Propionyl-CoA and L-methylmalonyl-CoA are intermediates in the conversion of these amino acids to succinyl-CoA. Methyl-malonyl-CoA mutase is a vitamin B 12-requiring enzyme. Note that threonine is also degraded via the propionyl-CoA/suc-cinyl-CoA pathway (see Figure 15.4). 

About ten coenzyme Bi2-dependent enzymes are now known (see Table 1) [6, 25,153,173]. These enzymes are four carbon skeleton mutases (methyl-malonyl-CoA mutase [174], glutamate mutase [175,176], methylene glutarate mutase [175] and isobutyryl-CoA mutase [177]), diol dehydratase [178],... 

The homolytic cleavage of the Co - C bond of the protein-boimd organo-metallic cofactor AdoCbl (2) is the initial step of the coenzyme Bi2-catalyzed enzymatic reactions. Halpern quoted that adenosyl cobamides can be considered as reversibly functioning sources for organic radicals [119]. A neutral aqueous solution of 2 is remarkably stable with a half-Ufe of 10 s (in the dark at room temperature), but decomposes, mainly with the homolysis of the Co-C bond, at higher temperatures [119,123]. The coenzyme B12-catalyzed enzyme reactions occur with maximal rates of approximately 100 s [173,239]. Rapid formation of Co(ll)corrins occurs only with addition of substrate to a solution of holoenzyme (or of apoenzymes and 2), as demonstrated in most of the known coenzyme Bi2-dependent enzymes, e.g., in methyl-malonyl-CoA mutase [121], glutamate mutase [202] and ribonucleotide reductase [239]. 

Enzymes with vitamin B12 its coenzyme in human metabolism. (1) With adenosylcobalamine methyl-malonyl CoA-mutase (EC 5.4.99.2) leucine-2,3-ami-nomutase (EC 5.4.3.7) (2) with methylcobalamine tetrahydropteroyltriglutamate methyltransferase (EC 2.1.1.13). 

Of possible biological interest is the report, based on a model reaction study with hydroxocobalamine, that the coenzyme-B, 2-dependent methyl-malonyl-CoA mutase reaction could involve intramolecular addition of a primary radical to a thioester group. The cyclopropyloxy radical so formed in a Cy3/Cy4 case would open to the carbethoxy-substituted and hence stabilized radical to give the rearranged product. ... 

In humans, cobalamins are essential coenzymes for two cellular enzymes. One is the mitochondrial enzyme, methyl malonyl-coA-mutase, which converts methylmalonic acid (MMA) to succinyl-CoA. The other is the cytoplasmic methionine syntase, which converts homocysteine (Hey) to methionine (reviewed by Banerjee 2006). An insufficient amount of cobalamin in the cells, therefore, leads to increase levels of MMA and total homocysteine (tHcy). 

The methylmalonic acidemias [14, 15] are a family of disorders in the metaboUsm of branched-chain amino acids in which the activity of methyl-malonyl-CoA mutase is defective. They may be divided into mutase apoen-zyme defects and defects in cofactor synthesis or cobalamin metabolism. 

Goodman, S.I., McCabe, E.R.B., Fennessey, P.V., Miles, B.S., Mace, J.W. and Jellum, E. (1978), Methylmalonic/j8-hydroxy- -valeric acidemia due to methyl-malonyl CoA mutase deficiency. Clin. Chim. Acta, 87,441. 

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