title: 16 Inhibition of mammalian protein methyltransferases by 5'-methylthioadenosine (MTA): A mechanism of action of dietary same?
abstract: 5'-deoxy-5'-methylthioadenosine (5'-methylthioadenosine, MTA) is a naturally occurring metabolite. As an experimental reagent, it has proved useful in providing investigators a window onto the role of protein methylation reactions in intact cells, although its mode of action is poorly understood in most cases. This chapter reevaluates its utility as a reagent. It appears now that MTA is at best a poor direct inhibitor of methyltransferases and that its effectiveness in intact cells may depend on its ability to inhibit S-adenosyl-l-homocysteine hydrolase. This chapter reviews recent evidence that points to an important role for MTA as an intermediary in the beneficial pharmaceutical action of orally ingested S-adenosyl-l-methionine (AdoMet, SAMe). These new results suggest that oral AdoMet may function not by enhancing the activity of cellular methyltransferases, as has been previously surmised, but by inhibiting their action. Such inhibition, particularly of protein methyltransferases involved in intracellular communication, may attenuate signal transduction pathways otherwise leading to inflammatory damage to tissues.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute University of California, Los Angeles 405 Hilgard Avenue Los Angeles, CA 90095, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Clarke