Heterogeneity of carbonyl reduction in subcellular fractions and different organs in rodents.
The pattern and distribution of carbonyl reduction in liver, kidney and adrenal gland subcellular fractions of NMRI mice, Wistar rats and Hartley guinea pigs were examined using the ketone compound metyrapone (2-methyl-1,2-di(3-pyridyl)1-propanone) commonly used as a diagnostic cytochrome P450 inhibitor. A direct HPLC method for alcohol metabolite determination instead of the indirect spectrophotometric recording of pyridine nucleotide oxidation at 340 nm was applied. All the tissues examined in these species rapidly reduced the employed compound but at the subcellular level no general distribution scheme of specific activity was found, although in all fractions metyrapol formation could be attributed to aldo-keto reductases. Cytosolic and microsomal metyrapone reducing enzymes are distinguished by their inhibitor sensitivity to phenobarbitone and quercitrin and thus can be characterized as aldehyde and ketone reductases according to the inhibitor subclassification of the aldo-keto reductase family. Moreover, the enzymes also differ with respect to their immunological cross-reactivity to anti-microsomal mouse liver metyrapone reductase antibodies. Immunological homologies were found between metyrapone reductases of liver microsomes from all species and kidney and adrenal gland microsomes from guinea pig. However, the protein of all the cytosolic fractions as well as that of kidney and adrenal gland microsomes from mouse and rat did not cross-react with the antibodies, indicating the absence of common antigenic determinants. From catalytic properties and functional data it is concluded that hydroxysteroid dehydrogenases present in the suspected subcellular fractions form a structurally and functionally related enzyme family which may have been conserved during evolution.
Oppermann
U C
UC
Department of Pharmacology and Toxicology, School of Medicine, Philipps University, Marburg, Federal Republic of Germany.
Maser
E
E
Mangoura
S A
SA
Netter
K J
KJ
D000311:Adrenal Glands / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000449:Aldehyde Reductase / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000818:Animals; D006168:Guinea Pigs; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008797:Metyrapone / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology*
C012526:quercitrin; D011794:Quercetin; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse; D010634:Phenobarbital; D008797:Metyrapone