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Molecular Pharmacology, Vol 8, 189-196, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

An Approach Measurement of the Stoichiometric Relationship between Hepatic Microsomal Drug Metabolism and the Oxidation of Reduced Nicotinamide Adenine Dinucleotide Phosphate

B. STRIPP 1, N. ZAMPAGLIONE 1, M. HAMRICK 1, and J. R. GILLETTE 1

1 Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health Bethesda, Maryland 20014

Various methods for estimating the stoichiometric relationship between drug oxidation and NADPH oxidation in hepatic microsomes are discussed. Of these, two methods give values approaching 1:1 for a number of type I substrates. One method relates the metabolism to the substrate-dependent NADPH oxidation corrected for CO-sensitive, endogenous NADPH oxidation. The correction was obtained by measuring the rate of NADPH oxidation in an atmosphere of 9:1 CO-O2. The other method relates the CO-sensitive drug oxidation to CO-sensitive NADPH-oxidation.

Submitted on November 8, 1971







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