Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces japonicus. II. Characterization of illudin S-metabolizing enzyme.
1. Enzyme systems responsible for formation of cyclopropane ring-cleavage metabolites (M1 and M2) of illudin S in rat liver were characterized. 2. The enzymes were localized in the cytosol fraction and utilized NADPH alone as electron donor; they were not affected by oxygen and had low pH optima. 3. Formation of metabolites M1 and M2 was inhibited completely by dicumarol (10(-4) M), an inhibitor of DT-diaphorase. 4. Menadione (10(-4) M) and quercetin (10(-4) M) both inhibited formation of M1 and M2 by 35% and 15%, respectively, but quinacrine, barbital, pyrazole and p-chloromercuribenzoic acid had no significant effect. 5. Results show that the enzyme systems may differ from DT-diaphorase, aldehyde oxidase, xanthine oxidase, ketone reductase, aldose reductase, aldehyde reductase and alcohol dehydrogenase, known cytosolic enzymes responsible for xenobiotic metabolism.
Tanaka
K
K
National Research Institute of Police Science, Tokyo, Japan.
Inoue
T
T
Kadota
S
S
Kikuchi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D001728:Dicumarol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D000081223:Polycyclic Sesquiterpenes; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D014812:Vitamin K; D009249:NADP; D001728:Dicumarol; D011794:Quercetin; D016660:NAD(P)H Dehydrogenase (Quinone); C008105:illudin S; D010100:Oxygen