Oct 1, 1975

Explanation of the stimulation of microsomal N-demethylation reactions by soluble supernatant fraction

Research Communications in Chemical Pathology and Pharmacology
D L Cinti

Abstract

Addition of the cell soluble supernatant fraction to an assay medium containing NADPH generating system, mixed function oxidase substrate and microsomes, resulted in a stimulation of drug metabolism ranging from 12-75%. This stimulation was observed only when the supply of DADPH generating system (isocitric dehydrogenase or glucose 6 phosphate dehydrogenase) was insufficient, leading to a NADPH oxidation rate which was greater than the rate of reduction of NADP+ during the oxidation of a drug. Hence, under our assay conditions, the soluble supernate (SS) is only providing sufficient NADPH generator, and possibly relieving inhibition by the generated NADP+. Finally, microsomal lipid peroxidation measurements under these same conditions indicate negligible to no peroxidation activity in the absence of SS.

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Mentioned in this Paper

Aminopyrine N-Demethylase
Microsomes
G6PD
Ethylmorphine-N-Demethylase
Glucosephosphate Dehydrogenase
Microsomes, Liver
Oxidation
Dealkylation
Soluble
Supernatant

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