S-adenosylmethionine decarboxylase: structure, function and regulation by polyamines.

Introduction The aminopropyl groups in spermidine and spermine are obtained from S-adenosylmethionine (AdoMet) after its decarboxylation by the action of the enzyme S-adenosylmethionine decarboxylase (AcloMetDC) [ 1,2]. Once decarboxylated, AdoMet no longer serves as a methyl donor. AdoMetDC is, therefore, not only critical for polyamine biosynthesis but plays a key role in determining the disposition of the cellular AdoMet pools. AdoMetDC is very highly regulated with activity responding to stimuli that induce changes in polyamine content and to changes in the polyamine pools. The importance of such regulation in the disposition of AdoMet can be demonstrated by inhibiting the synthesis of polyamines with a-difluoromethylornithine. This prevents the synthesis of putrescine, and the aminopropyltransferases that form spermidine and spermine cannot then use the decarboxylated AdoMet (dcAdoMet). The decrease in polyamine concentration, however, leads to an elevation in AdoMetDC activity at a time when utilization of dcAdoMet is prevented. The combined effects of these changes are to increase decarboxylated AdoMet from approx. 1-2% of the AdoMet to 400% of the AdoMet content [2]. This paper provides an overview of the structure, function and regulation of mammalian AdoMetDC. Several more detailed reviews of this enzyme and the polyamine pathway are available and provide complete citation lists for this topic [3-61.