Carbonyl reduction of an anti-insect agent imidazole analogue of metyrapone in soil bacteria, invertebrate and vertebrate species

• Published in: Chemico-biological interactions 1998-07, Vol.114 (3), p.211-224
• Main Authors: Oppermann, Udo C.T, Nagel, Gerd, Belai, Ivan, Bueld, Juliane E, Genti-Raimondi, Susanna, Koolman, Jan, Netter, Karl J, Maser, Edmund
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - antagonists & inhibitors; Alcohol Oxidoreductases - metabolism; Aldehyde Reductase; Aldo-Keto Reductases; Animals; Antibody Specificity; Bacteria - enzymology; Bacteria - metabolism; Bacteria - ultrastructure; Biodegradation, Environmental; Blotting, Western; Carbonyl reduction; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Hydroxysteroid dehydrogenases; Hydroxysteroid Dehydrogenases - antagonists & inhibitors; Hydroxysteroid Dehydrogenases - metabolism; In Vitro Techniques; Insecticides - chemistry; Insecticides - metabolism; Invertebrates - enzymology; Invertebrates - metabolism; Invertebrates - ultrastructure; Medicin och hälsovetenskap; Metyrapone - analogs & derivatives; Metyrapone - chemistry; Metyrapone - metabolism; Oxidation-Reduction; Short-chain dehydrogenases; Soil Microbiology; Subcellular Fractions - enzymology; Subcellular Fractions - metabolism; Vertebrates - metabolism; Xenobiotic metabolism
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/S0009-2797(98)00057-X

Carbonyl reduction to the respective alcohol metabolites of the anti-insect agent imidazole analogue of metyrapone, NKI 42255 (2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone) and its parent compound metyrapone was characterized in subcellular fractions from soil bacteria, as well as insect, invertebrate and teleost species. The enzymes involved in this metabolic step were characterized with respect to their cosubstrate specificities, inhibitor susceptibilities, and immunological crossreactivities with antibodies directed against previously described bacterial and mammalian hydroxysteroid dehydrogenases/carbonyl reductases (HSD/CR). All fractions investigated rapidly reduced metyrapone, with highest specific activities found in insect, invertebrate and vertebrate fractions. Except for the insect fractions, all species examined reduced the NKI compound. Cosubstrate dependence and inhibitor specificities suggest that the enzymes described belong to the protein superfamilies of short-chain dehydrogenases/reductases (SDR) or aldo-keto reductases (AKR). Immunological crossreactions to the previously established subgroup of HSD/CRs were found in trout liver microsomes and insect homogenates, but not in all bacterial extracts or earthworm microsomes. These findings suggest that the high CR activities found in these fractions belong to different subgroups of SDR or AKR.