Vitamin leucine aminomutase

Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase (Figure 45-14) are vitamin Bj2-dependent enzymes. Methylmalonyl CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and, rarely, fatty acids with an odd number of carbon atoms—or directly from propionate, a major product of microbial fer-... 

In mammals, there are only three vitamin B12 -dependent enzymes methionine synthetase, methylmalonyl CoA mutase, and leucine aminomutase. The enzymes use different coenzymes methionine synthetase uses methylcobal-amin, and cobalt undergoes oxidation during the reaction methylmalonyl CoA mutase and leucine aminomutase use adenosylcobalamin and catalyze the formation of a 5 -deoxyadenosyl radical as the catalytic intermediate. 

Leucine catabolism also occurs by a second, minor pathway. The first step in this pathway is catalyzed by leucine aminomutase (Poston, 1984). Leucine ami-nomutasc is one of the three vitamin Bjj-requiring enzymes in mammalian tissues. 

Vitamin Bu is unique among all the vitamins in that it is the largest and most complex and because it contains a metal ion. 1 hismetal ion is cobalt. Cobalt occurs in three oxidation states Co, Co, and Co. The medicinal forms of the vitamin are cyanocobalamin and hydnoxocobalamin. In cyanocobalamin, a molecule of Cyanide is complexed to the Co atom. Cyanocobalamin is readily converted in the body to the cofactor forms methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin contains cobalt in the Co slate, where it acts as a cofactor for methionine synthase. 5 Deoxyadenosylcobalamin, which contains cobalt in the Co state, is the cofactor for methylmalonyl-CoA mutase. Vitamin Btj is also a cofactor for leucine aminomutase, anen7yme used in leucine metabolism (Poston, 1984). This enzyme appears not to have a vital function in metabolism. No more... 

In 1980 Poston (PI) proposed that vitamin B12 was required for the conversion of the branched-chain amino acid p-leucine to leucine. He found circulating P-leucine levels elevated in patients with vitamin B12 deficiency. The concentration of leucine on the other hand was found to be much lower. He suggested that 2,3-aminomutase, which catalyzes the interconversion of P-leucine and leucine, is a vitamin B12-dependent enzyme which is consequently reduced in patients with pernicious anemia. The enzyme has been found in the liver of several animals and in human leucocytes, and in vitro experiments have shown it to be adenosylcobalamin dependent (P2). 

Poston (1984) showed that, in isolated rat tissues, about 5% of the catabolic flux of leucine was by way of aminomutase action to yield /S-leucine, and then isobutyryl CoA, with the remainder provided by the more conventional a-transamination pathway leading to the formation of isovaleryl CoA. In patients suffering from vitamin B12 deficiency, there is an elevation of plasma /S-leucine, suggesting that the aminomutase may act to metabolize /S -leucine arising from intestinal bacteria, rather than as a pathway for leucine catabolism. 

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