Effect of Temperature on the Relationship Between Hepatic Microsomal Cytochrome P-450 Reduction and Ethylmorphine Demethylation

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Abstract
The rate of reduction of hepatic microsomal cytochrome P-450 (NADPH-cytochrome P-450 reductase activity) was studied at temperatures ranging from 15 to 50°C. Ethylmorphine stimulated the initial , rate of cytochrome P-450 reduction at all temperaturesexamined. Parallel studies of the temperature dependence of microsomal ethylmorphine N-demethylase revealed a proportionality between ethylmorphine N-demethylase and cytochrome P-450 reductase activities at temperatures below 40°C. This finding is in accord with the view that the rate of microsomal P-450 reduction by NADPH is the rate-limiting step in the oxidation of drugs by microsomal enzymes.