Menadione inhibition of benzo(a)pyrene metabolism in whole cells, microsomes and reconstituted systems.
Menadione is known to decrease the mixed function oxidase mediated metabolism of a number of substrates in microsomal systems. 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. Menadione has a high affinity for the NADPH dependent cytochrome P-450 reductase and acts as a competitive inhibitor of cytochrome P-450 reductase in the metabolism of benzo(a)pyrene. This is the mechanism of inhibition of aryl hydrocarbon hydroxylase by menadione in reconstituted systems. In a whole cell system and at low concentrations of menadione, depletion of reduced pyridine nucleotides is the initial inhibitory event.
I J
IJ
Sadowski
J A
JA
Wright
D
D
Ollmann
L G
LG
Israels
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002460:Cell Line; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014812:Vitamin K / Q000494:pharmacology*
D014812:Vitamin K; D001564:Benzo(a)pyrene; D006899:Mixed Function Oxygenases