REGULATION OF S-ADENOSYL-L-METHIONINE DECARBOXYLASE BY 1-AMINOOXY-3-AMINOPROPANE - ENZYME-KINETICS AND EFFECTS ON THE ENZYME-ACTIVITY IN CULTURED-CELLS

The kinetics of inactivation of adenosy lmethionine decarboxy lase of rat liver and of baby hamster kidney cells (BHK21/C31) by l-aminooxy-3-aminopropane was studied. The apparent dissociation constants (Kt) for the hepatic and BHK21/C13 enzymes were 1.5 and 2.0 mM and the times of half-inactivation at infinite concentration of the inhibitor (ri/2) were 1.2 and 3.8 min, respectively. Treatment of BHK21/C13 with 0.5 mM l-aminooxy-3-aminopropane prevented cell growth and depleted the cells of putrescine and spermidine within 1 day. The depletion of spermidine resulted in increased activity of S-adenosy 1-methionine decarboxylase which was due, at least partly, to the increase in the half-life of the enzyme activity. Because spermine levels were not significantly affected, it appears that spermidine is the principal feedback regulator of S-adenosylmethionine decarboxylase. So, l-aminooxy-3-aminopropane is a very weak inhibitor of S-adenosylmethionine decarboxylase and the cellular effects can be correlated primarily with its inhibitory effects on ornithine decarboxylase and spermidine synthase. In cell-free systems, however, l-aminooxy-3-aminopropane is likely to find use in unraveling the reaction mechanism of S-adenosylmethionine decarboxylase. © 1990 COPYRIGHT, 1990 BY THE JOURNAL OF BIOCHEMISTRY.