Abstract
Ornithine decarboxylase (ODC) is the initial enzyme in the polyamine synthetic pathway, and polyamines are required for cell proliferation. We have shown previously that nitric oxide (NO) inhibits ODC activity in Caco-2 cells and in crude cell lysate preparations. In this study we examined the mechanism by which NO inhibits the activity of purified ODC. NO, in the form of S-nitrosocysteine (CysNO), S-nitrosoglutathione (GSNO), or 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine (DEA/NO), inhibited enzyme activity in a concentration-dependent manner. CysNO (1 μM) inhibited ODC activity by approximately 90% and 3 μM GSNO by more than 70%. DEA/NO was less potent, inhibiting enzyme activity by 70% at a concentration of 30 μM. Inhibition of enzyme activity by CysNO, GSNO, or DEA/NO was reversible by addition of dithiothreitol or glutathione. Cuprous ion (Cu (I)) also reversed the inhibitory effect of these NO donor agents. The data presented here support the hypothesis that NO inhibits ODC activity via S-nitrosylation of a critical cysteine residue(s) on ODC.
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