Purification and characterization of chlordecone reductase from human liver.
The toxic organochlorine pesticide, chlordecone (Kepone), is excreted in human bile primarily as a stable, reduced monoalcohol metabolite. This bioreduction is catalyzed by a hepatic cytosolic enzyme activity termed chlordecone reductase. We purified this enzyme from human liver and found that chlordecone reductase resembles the family of xenobiotic metabolizing enzymes referred to as the aldo-keto reductases based on its biochemical characteristics, including its ability to catalyze the reduction of a carbonyl-containing substrate. However, analyses of liver cytosolic samples on immunoblots developed with anti-chlordecone reductase antibodies revealed that immunoreactive proteins were present only in those mammalian species that convert chlordecone to chlordecone alcohol in vivo (man, gerbil, and rabbit) and not in those species unable to reduce chlordecone (rat, mouse, and hamster). Hence, chlordecone reductase is unique among aldo-keto reductases in being species-specific. Quantitative immunoblot analyses of seven human liver specimens disclosed two immunoreactive proteins whose total concentration varied over a 6-fold range. Moreover, the amount of immunoreactive protein was directly proportional to chlordecone reductase activity in each sample. We conclude that chlordecone reductase is a unique aldo-keto reductase of potential clinical importance whose expression varies markedly among individuals.
D000429:Alcohol Oxidoreductases / Q000302:isolation & purification*; D001646:Bile / Q000378:metabolism; D007631:Chlordecone / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007106:Immune Sera; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; D010084:Oxidation-Reduction
D007106:Immune Sera; D000429:Alcohol Oxidoreductases; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; C048321:chlordecone reductase; D007631:Chlordecone