Metabolism of diamantane by rat liver microsomal cytochromes P-450.
1. Diamantane binds to liver microsomes from phenobarbital-treated rats with an apparent Ks value of 5.2 x 10(-7) mol/l. This value being lower than that obtained for perhydrophenanthrene indicates that diamantane is very strongly bound to microsomal cytochrome P-450. 2. Metabolic studies show that liver microsomes from phenobarbital-treated rats readily metabolize diamantane to mono-, di- and possibly tri-hydroxy derivatives, whereas liver microsomes from beta-naphthoflavone-induced rats do not bind this hydrocarbon or metabolize it. 3. Reconstituted cytochromes P-450 b and e were more efficient in the hydroxylation of diamantane than liver microsomes; metabolites formed by the reconstituted system do not include all the products formed by microsomes, which indicates the involvement of forms of cytochrome P-450 other than the isozymes b and e.
Hodek
P
P
Department of Biochemistry, Charles University, Czechoslovakia.
Janscák
P
P
Anzenbacher
P
P
Burkhard
J
J
Janků
J
J
Vodicka
L
L
D000218:Adamantane / Q000493:pharmacokinetics*; D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D000218:Adamantane; D010634:Phenobarbital