Inhibition of NADPH Oxidation and Related Drug Oxidation in Liver Microsomes by Zinc
Document Type
Article
Publication Date
8-1-1976
Description
Rat liver microsomes were incubated in the presence of zinc and the rate of NADPH oxidation and related metabolism of aniline and ethylmorphine by appropriate oxidases were studied. A competitive mechanism of the inhibition of NADPH oxidation by zinc was found, with Vmax = 10.3 nmoles NADP/min/mg of protein and Ki amounting to 7.22 μM zinc. In microsomes dialyzed against EDTA, addition of Mn2+ but not of Mg2+ enhanced the rate of NADPH oxidation. A complex relation of Zn2+ and Mn2+ in liver microsomes was found, the data not obeying the rigorous treatment for enzyme kinetics. The activity of aniline hydroxylase and ethylmorphine-N-demethylase was inhibited by zinc; 50 per cent inhibition was reached at 60 and 55 μM Zn2+ respectively. Another microsomal enzyme, glucose 6-phosphatase, independent of NADPH, was not affected by zinc. The content and spectral characteristics of cytochrome P-450 were not affected by zinc. It is concluded that Zn2+ inhibits oxidation of NADPH and prevents this pyridine nucleotide from functioning in the microsomal electron transport system. The possibility that Zn2+ may interfere with other ions or enzymes involved in microsomal electron transport cannot be excluded.
Citation Information
Chvapil, Milos; Ludwig, Janet C.; Sipes, I. Glenn; and Misiorowski, Ronald L.. 1976. Inhibition of NADPH Oxidation and Related Drug Oxidation in Liver Microsomes by Zinc. Biochemical Pharmacology. Vol.25(15). 1787-1791. https://doi.org/10.1016/0006-2952(76)90417-2 PMID: 8050 ISSN: 0006-2952