Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces japonicus. II. Characterization of illudin S-metabolizing enzyme

Abstract

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 (10⁻⁴M), an inhibitor of DT-diaphorase.

4. Menadione (10⁻⁴M) and quercetin (10⁻⁴M) 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, aldéhyde reductase and alcohol dehydrogenase, known cytosolic enzymes responsible for xenobiotic metabolism.