CARBONYL REDUCTION OF AN ANTIINSECT AGENT IMIDAZOLE ANALOG OF METYRAPONE IN SOIL BACTERIA, INVERTEBRATE AND VERTEBRATE SPECIES

Carbonyl reduction to the respective alcohol metabolites of the anti-i nsect agent imidazole analogue of metyrapone, NKI 42255 dazolyl)-1-(4- methoxyphenyl)-2-methyl-1-propanone) and its parent compound metyrapon e was characterized in subcellular fractions previously described bact erial and mammalian hydroxysteroid dehydrogenases/carbonyl from soil b acteria, as well as insect, invertebrate and teleost species. The enzy mes involved in this metabolic step were characterized with respect to their cosubstrate specificities, inhibitor susceptibilities, and immu nological crossreactivities with antibodies directed against reductase s (HSD/CR). All fractions investigated rapidly reduced metyrapone, wit h highest specific activities found in insect, invertebrate and verteb rate fractions. Except for the insect fractions, all species examined reduced the NKI compound. Cosubstrate dependence and inhibitor specifi cities suggest that the enzymes described belong to the protein superf amilies of short-chain dehydrogenases/reductases (SDR) or aldo-keto re ductases (AKR). Immunological crossreactions to the previously establi shed subgroup of HSD/CRs were found in trout liver microsomes and inse ct homogenates, but not in all bacterial extracts or earthworm microso mes. These findings suggest that the high CR activities found in these fractions belong to different subgroups of SDR or AKR. (C) 1998 Elsev ier Science Ireland Ltd. All rights reserved.