"Inhibition of NADPH Oxidation and Related Drug Oxidation in Liver Micr" by Milos Chvapil, Janet C. Ludwig et al.
 

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.

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