BIOLOGICAL EFFECTS OF INHIBITORS OF S-ADENOSYLHOMOCYSTEINE HYDROLASE

S-Adenosylhomocysteine (AdoHcy), formed after the donation of the meth yl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed t o adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or anima ls normally results in an accumulation of cellular AdoHcy higher than those found in controls, which is often accompanied by a simultaneous rise in S-adenosylmethionine because of the feedback inhibition by Ado Hcy on most methylation reactions, AdoHcy hydrolase has become a tanta lizing pharmacological target for inhibition since its blockade can af fect:cellular methylation of phospholipids, proteins, small molecules, DNA, and RNA, Indeed, all of these different methylation reactions ha ve been found to be inhibitable by the nucleoside inhibitors/substrate s of AdoHcy hydrolase, Among the interesting effects are the activatio n of genes, induction of cellular differentiation, increased expressio n of transcription factors, and sometimes the repression of genes, Fur thermore, some of the nucleosides show remarkable antiviral activities in vitro and in vivo. However, the mode of action of the inhibitors a ppears complex, Although the inhibition of methylation might account f or some of the biological effects, the ability of some of the nucleosi de inhibitors to undergo metabolic phosphorylation to nucleotides may account for part of their biological activities, The defining mode of action responsible for their biological effects still awaits biochemic al elaboration, especially regarding their antiviral effects, inductio n of genes, or cellular differentiation. Published by Elsevier Science Inc.