Model Studies for the B12 Dependent Methyltransferases
Methytransferases having coenzyme B12 and other Co-eorrinoids as cofactors, catalyze important methyl transfer reactions (1,2). The synthesis of methionine, in most animals including mammals and many bacteria, involves the transfer of the methyl group from Me-tetrahydrofolate to Cob(I)alamin and subsequently to homocysteine (3). In acetogenic bacteria, the transfer from Me-tetrahydrofolate to Co(I) is followed by further reaction with CO and RSH in a Co-Ni dependent enzyme (4). In methanogenic bacteria, corrinoids are involved in the synthesis of coenzyme M and can use methanol and Me-tetrahydrofolate as methyl sources. Methanol is also the methyl donor in other acetogenic bacteria (5). The enzymatic reaction catalyzed by methionine synthase is shown in Scheme 1; in the first half-reaction, Co(I) acts as a supernucleophile for the substrate bearing the CH3-group, Me-THF, whereas it becomes an efficient leaving group in the second half-reaction. In the latter step, the methyl cob(III)alamin reacts with homocysteine to form methionine and regenerate the Cob(I)alamin (6).
KeywordsPyridine Methionine Thiol Homocysteine Clostridium
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