Abstract
1. 1. Menadione is known to decrease the mixed function oxidase mediated metabolism of a number of substrates in microsomal systems. 2. 2. The present study examines the effect of menadione on benzo(a)pyrene metabolism in whole cells, microsomes and a semi-purified reconstituted mixed function oxidase system. 3. 3. Menadione has a high affinity for the NADPH dependent cytochrome - P450 reductase and acts as a competitive inhibitor of cytochrome P-450 reductase in the metabolism of benzo(a)pyrene. 4. 4. This is the mechanism of inhibition of aryl hydrocarbon hydroxylase by menadione in reconstituted systems. 5. 5. In a whole cell system and at low concentrations of menadione, depletion of reduced pyridine nucleotides is the initial inhibitory event.
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