Concerning the nonspecificity of methylation inhibitors

Most of the evidence for the essential participation of S-adenosylmethionine (AdoMet)-mediated methylation reactions in eukaryotic cell functions derives from the use of chemical probes that have been found to be inhibitory to these various cell functions and that are also known to be inhibitory, in a direct or an indirect manner, to some cellular methylation reaction(s). Compounds most often employed experimentally as methylation reaction probes include adenosine (Ado), 3-deazaadenosine (c3Ado), 5'-deoxy-5'-S-isobutylthioadenosine (SIBA) and 5'-deoxy-5'-S-isobutylthio-3-deazaadenosine (c3SIBA). The use of all these compounds as methylation reaction probes is based upon the findings of numerous investigators that S-adenosylhomocysteine (AdoHcy) is a potent inhibitor of many AdoMet-utilizing methyltransferases (see review by Borchardt, 1977). In many of the studies employing Ado and c3Ado, L-homocysteine (Hcy) has been observed to potentiate the physiological effects of these nucleosides (e.g., Ishizaka et al., 1980; Morita et al., 1981; Pike et al., 1978; Rabe et al., 1980; Zimmerman et al., 1978). This potentiation by Hcy has been interpreted as additional evidence that Ado and c3Ado are affecting cell function as the result of an intracellular buildup of AdoHcy or S-3-deazaadenosylhomocysteine (c3AdoHcy), respectively, and consequent inhibition of one or more methyltransferases.KeywordsMethylation ReactioncAMP PhosphodiesteraseAffect Cell FunctioncAMP MetabolismAdenosine Deaminase InhibitorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.