Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultures of BHK-21/C13 cells, whose growth was inhibited by deprivation of serum, were stimulated to grow by addition of serum to the culture medium. Addition of MgCl(2) to the medium, to increase the concentration of Mg(2+) ions by 15mm, 30min before addition of serum, had no effect on the stimulation of cell growth, but inhibited the accumulation of cellular spermidine, so that the spermidine/spermine molar ratio was lower in these cultures than in cultures that had received no additional cations. The increase in the activity of ornithine decarboxylase that occurs 4-5h after serum ;step-up' was substantially diminished by increasing the concentration of Mg(2+) ions, but not of Na(+) or K(+) ions, in the medium by 30mm, 30min before addition of serum, and this inhibition was maintained for at least 24h. Methylglyoxal bis(guanylhydrazone), added to serum-deprived cultures to a concentration of 20mum, 30min before addition of serum, severely inhibited the increase in cell growth. The inhibitory effects of the drug were prevented by simultaneous addition of spermidine to the medium (to 100mum), and were partly prevented by the simultaneous addition of Mg(2+) ions (to 30mm). Mg(2+) ions were particularly effective in overcoming the inhibitory effect of methylglyoxal bis(guanylhydrazone) on the synthesis of DNA. Thus although a certain lack of specificity for cations exists in BHK-21/C13 cells, in that Mg(2+) ions can be substituted for polyamines, particularly spermidine, to some extent, there are cellular processes for which the requirement for polyamines as cations is specific.
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PMID:Polyamine replacement by magnesium ions in BHK-21/C13 cells. 44 20

The uptake, catabolism, and release of H-labeled 1-aminooxy-3-aminopropane, a new putrescine analog shown to be a potent polyamine antimetabolite, into and from baby hamster kidney cells (BHK21/C13) were studied. The results show that [3H]-1-aminooxy-3-aminopropane (APA) is not concentrated in the cell, does not compete with polyamines for transport and reveals no difference in uptake between polyamine-depleted and control cells. After a 12-h culture, 60% of APA was recovered intact in the culture media. At this time point, only 30% of the intracellular radioactivity was intact APA, showing that the drug is catabolized in the cells. This intracellular ratio persisted throughout the 4-day culture period. The metabolites of APA were not characterized further. The results indicate that the drug is not recognized as a polyamine by the cells and does not replace or interfere with the polyamines in cellular functions. Thus, its potent affinity to ornithine decarboxylase and spermidine synthase is likely to be due to close structural similarity with the intermediates formed in these reactions. This has implications for the mechanisms involved.
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PMID:Uptake of 3H-labeled 1-aminooxy-3-aminopropane by baby hamster kidney cells. 211 37

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.
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PMID:Regulation of S-adenosyl-L-methionine decarboxylase by 1-aminooxy-3-aminopropane: enzyme kinetics and effects on the enzyme activity in cultured cells. 234 68

1- or 3-methylated derivatives and oximes of 1-aminooxy-3-aminopropane (APA) with pyridoxal (PL) and pyridoxal 5'-phosphate (PLP) were synthesized to examine whether the stability of the parent APA molecule could be increased without loss of its inhibitory capacity towards ornithine decarboxylase. Preformed APA-PLP was more stable than APA and was not a substrate of cellular acetylating activity. The only detectable degradation mechanism of APA-PLP was a slow dephosphorylation to APA-PL, which was a substrate for cellular acetylating activity like the methylated APA derivatives. Methylation at the 1 or 3 position of APA did not increase its stability but markedly changed its inhibitory potency towards S-adenosylmethionine decarboxylase and spermidine synthase. Supplementation of cell growth media with 1 mM aminoguanidine markedly reduced the degradation rate of 1- or 3-Me-APA and APA. All the growth-retarding effects of the drugs were reversed by addition of 10-20 microM putrescine or spermidine to the growth media containing a drug concentration of 1 mM, except with APA-PL, which had signs of emergent toxicity at concentrations above 0.5 mM. APA-PL and APA-PLP were as good as APA and two orders of magnitude more effective than alpha-difluoromethylornithine (DFMO) in inhibiting DNA synthesis by BHK21/C13 cells.
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PMID:Derivatives of 1-aminooxy-3-aminopropane as polyamine antimetabolites: stability and effects on BHK21/C13 cells. 789 33