Properties of human and rodent S-adenosylmethionine decarboxylase.

Abstract

S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the biosynthesis of the polyamines spermidine and spermine. Its product, decarboxylated S-adenosylmethionine (dcAdoMet) is used as an aminopropyl donor by spermidine synthase and spermine synthase (Williams-Ashman and Pegg, 1981; Pegg and McCann, 1982; Tabor and Tabor, 1984a). Once decarboxylated by the action of AdoMetDC, S-adenosylmethionine (AdoMet) becomes committed to polyamine production since methyltransferases use dcAdoMet very poorly, if at all (Pegg, 1984, 1986). In fact, the only known metabolic route for further metabolism of dcAdoMet apart for its use as an aminopropyltransferase substrate is its acetylation (Wagner et al., 1985; Pegg et al., 1986) The supply of dcAdoMet is normally regulated very tightly by the cellular polyamine content and this regulation is brought about by changes in the activity of AdoMetDC (Pegg, 1984). In this way, the cellular content of dcAdoMet is usually kept very low (about 1–3% of AdoMet content) as its synthesis is linked to the ability of the aminopropyltransferases to use it to form polyamines. Only when cellular polyamine metabolism is deranged by inhibition of the other enzymes in the polyamine biosynthetic pathway does the dcAdoMet content rise. Increases of several hundred fold occur when ornithine decarboxylase (ODC) activity is inhibited by drugs such as α-difluoromethylornithine (DFMO) and, only under these conditions, is the acetyl derivative of dcAdoMet formed in significant amounts (Pegg, 1986). The increased content of dcAdoMet is due to both an increase in the activity of AdoMetDC (Alhonen-Hongisto, 1980; Mamont et al., 1981; Pegg, 1984) and to the inability of the aminopropyltransferases to utilize the dcAdoMet formed by it because of the absence of putrescine and spermidine to serve as aminopropyl acceptors.