[The role of vitamin K3 in the hydroxylation of benz(a)pyrene in rat liver mitochondria after induction with 3-methylcholanthrene and phenobarbital].
The "fast" phase reduction of microsomal cytochromes P-450 and P-448 and their benz(a)pyrene (BP) hydroxylase activity was investigated as a function of menadione concentrations. Within a narrow concentration range (1.5-3 microM) menadione activates cytochrome P-448 reduction and the BP hydroxylase activity. At higher concentrations menadione inhibits cytochromes P-450 and P-448 reduction and BP hydroxylation with participation of the both cytochromes. These data suggest that menadione molecules present in membrane lipids serve as an additional electron carrier to cytochrome P-448, the active site of which is embedded into lipids. The activating effect is unobserved is case of cytochrome P-450 with an active site localized in the aqueous phase. The number of different BP metabolites formed at low (3 microM) menadione concentrations in the microsomes of rats induced with 3-methylcholanthrene (MC) and phenobarbital (PB) was compared. In PB-induced microsomes the amount of 7,8-dihydrodiol rises whereas the total content of BP metabolites decreases. Contrariwise, in MC-induced microsomes the synthesis of all BP metabolites is augmented. Menadione has a very weak effect on the ratio of different BP metabolites in PB- and MC-microsomes, but strongly inhibits the formation of more polar metabolites. This results in a marked reduction of the number of "dangerous" BP diolepoxides.
Izotov
M V
MV
Shcherbakov
V M
VM
Devichenskiĭ
V M
VM
Lugovaia
L V
LV
Benediktova
S A
SA
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003580:Cytochromes / Q000096:biosynthesis; D004790:Enzyme Induction; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009249:NADP; D010084:Oxidation-Reduction; D010634:Phenobarbital; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D014812:Vitamin K / Q000494:pharmacology*
D003580:Cytochromes; D014812:Vitamin K; D001564:Benzo(a)pyrene; D009249:NADP; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital
Uchastie vitamina K3 v gidroksilirovanii benz(a)pirena v mikrosomakh pecheni krys pri induktsii 3-metilkholantrenom i fenobarbitalom.