PMID: 2497733Apr 15, 1989Paper

Cellular characterization of a new irreversible inhibitor of S-adenosylmethionine decarboxylase and its use in determining the relative abilities of individual polyamines to sustain growth and viability of L1210 cells

The Biochemical Journal
Debora L KramerCarl W Porter

Abstract

S-(5'-Deoxy-5'-adenosyl)methylthioethylhydroxylamine (AMA) is an irreversible inhibitor of S-adenosylmethionine (AdoMet) decarboxylase, which is designed to bind covalently the pyruvate residue at the enzyme active site. In the present study the cellular effects of AMA were characterized for the first time in cultured L1210 leukaemia cells. At the approximate IC50 (concn. giving 50% inhibition; 100 microM), AMA decreased spermidine and spermine by more than 80% at 48 h while increasing putrescine more than 10-fold. As an indication of enzyme specificity, growth inhibition was fully prevented with exogenous spermidine. When compared with the irreversible inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (DFMO), at similar growth-inhibitory concentrations, AMA was less cytotoxic, as determined by colony-formation efficiency. In combination with AMA, DFMO eliminated the rise in putrescine and decreased growth in an additive manner. The near-total depletion of intracellular polyamine pools achieved with the drug combination provided an opportunity to examine the relative abilities of individual polyamines to support growth and viability. Of the three exogenously supplied polyamines, only spermidine fully sustained...Continue Reading

Citations

May 1, 1993·Journal of Cellular Physiology·D L KramerC W Porter
Feb 1, 1994·Journal of Cellular Physiology·M E TomeE W Gerner
Dec 22, 2006·Bioorganicheskaia khimiia·A R SimonianA R Khomutov
Aug 1, 1991·Annals of Medicine·J JänneP Leinonen
Feb 5, 2014·Biochemistry. Biokhimii︠a︡·M A KhomutovS N Kochetkov
Feb 3, 1995·The Journal of Biological Chemistry·D KramerC W Porter
Jan 25, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·Q YuanL R Johnson
Dec 21, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·Q YuanL R Johnson
Dec 20, 2007·The Journal of Biological Chemistry·Debora L KramerCarl W Porter
Dec 1, 1992·Pharmacology & Therapeutics·A E Pegg, P P McCann
Jun 1, 1992·Microbiological Reviews·R H DavisP Coffino
Jan 5, 2001·Journal of Medicinal Chemistry·R A Casero, P M Woster
May 1, 1990·Archives of Biochemistry and Biophysics·J Pitkin, R H Davis

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