The Birth and Demise of Hypotheses on Evolution of S-Adenosyl-Lmethionineand Adenosylcobalamin

Relationships between adenosylcobalamin and S-adenosyl-Lmethionine (SAM)-dependent enzymatic radical reactions are explored with a view toward determining their evolutionary relationships. Adenosylcobalamin is a Vitamin B12-coenzyme, and the vitamin deficiency causes pernicious anemia in humans. Methionine, the precursor of SAM, is a nutritionally essential amino acid. Evidence implicates both SAM and adenosylcobalamin in the generation of the 5’-deoxyadenosyl radical as the initiator of carbon-centered radical chemistry. However, expectations of the evolutionary superiority of the structurally and chemically complex adenosylcobalamin as an initiator of radical biochemistry are contradicted by available information. It is pointed out that adenosylcobalamin functions equally well aerobically and anaerobically, whereas SAM requires strong reducing conditions and electron transfer mediated by a [4Fe–4S]1+ cluster to initiate carboncentered radical chemistry.