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 adenosylmethionine decarboxylase of rat liver and of baby hamster kidney cells (BHK21/C31) by 1-aminooxy-3-aminopropane was studied. The apparent dissociation constants (Ki) 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 (tau 1/2) were 1.2 and 3.8 min, respectively. Treatment of BHK21/C13 with 0.5 mM 1-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-adenosylmethionine 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, 1-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, 1-aminooxy-3-aminopropane is likely to find use in unraveling the reaction mechanism of S-adenosylmethionine decarboxylase.
Hyvönen
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Department of Biochemistry, University of Kuopio, Finland.
Eloranta
T O
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D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002455:Cell Division; D002474:Cell-Free System; D002478:Cells, Cultured; D006224:Cricetinae; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines / Q000494:pharmacology*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors
D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines; D012436:S-Adenosylmethionine; C046252:1-aminooxy-3-aminopropane; D011436:Spermidine Synthase; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D013095:Spermidine; D011700:Putrescine