Purification and characterization of aldo-keto reductases from gerbil liver: immunochemical evidence for related proteins in other mammalian species.
We purified a hepatic aldehyde reductase (AR1) and two carbonyl reductases (CR1, CR2) from the Mongolian gerbil, an animal recently shown to closely resemble man in its metabolism of a carbonyl containing organochlorine pesticide. The apparent molecular weights of AR1, CR1, and CR2 were 40,700, 33,000, and 34,700, respectively. Typical of similar enzymes in other species, gerbil AR1 reduced aliphatic and aromatic aldehydes and was inhibited by phenobarbital or valproate, whereas CR1 and CR2 catalyzed the reduction of aromatic aldehydes and ketones as well as quinones and were inhibited by p-chloromercuribenzoate, mercuric chloride, or pyrazole. All three enzymes were insensitive to metal chelating agents and utilized NADPH as their cofactor. CR1 was unique in being equally active with NADH as its cofactor. Antibodies raised against CR1 reacted with purified CR1 and CR2, but not with AR1, as judged by immunoblot analyses. There were three immunochemically related proteins in gerbil liver cytosol (30 to 35 kDa range) recognized by the anti-CR1 IgG. Similar immunoblot analyses of hepatic cytosolic proteins from other mammalian species revealed immunoreactive proteins only in the hamster, the rabbit, and man, and not in the rat, the mouse, or the guinea pig. Quantitative immunoblot analyses of human liver cytosol from seven patients revealed three immunoreactive proteins. These were present in unequal and varying concentrations, although there were only small interindividual differences in the total concentration of the immunoreactive proteins. We conclude that there are multiple molecular forms of immunochemically related hepatic carbonyl reductases in the gerbil and in some other mammalian species, including man.
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D002848:Chromatography, DEAE-Cellulose; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D005849:Gerbillinae / Q000378:metabolism*; D006168:Guinea Pigs; D007120:Immunochemistry; D008099:Liver / Q000201:enzymology*; D008647:Mesocricetus; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse