Radical Mechanisms in Adenosylmethionine- and Adenosylcobalamin-Dependent Enzymatic Reactions

A class of enzymatic reactions of S-adenosylmethionine (AdoMet) has recently been recognized, in which AdoMet plays a novel role by initiating free radical formation through the intermediate formation of 5′-deoxyadenosine-5′-yl, the 5′-deoxyadenosyl radical. The reactions are in this way related to adenosylcobalamin-dependent processes, which also depend on the formation of the 5′-deoxyadenosyl radical as an intermediate. The mechanisms by which the 5′-deoxyadenosyl radical is generated by the AdoMet- and adenosylcobalamin-dependent enzymes are very different. However, the functions of the 5′-deoxyadenosyl radical are similar in that in all cases it abstracts hydrogen from a substrate to form 5′-deoxyadenosine and a substrate-derived free radical. In this paper, the role of the 5′-deoxyadenosyl radical in the reaction of the adenosylcobalamin-dependent reactions will be compared with its role in the AdoMet-dependent reaction of lysine 2,3-aminomutase. The mechanism by which AdoMet is cleaved to the 5′-deoxyadenosyl radical at enzymatic sites will also be discussed.