Saturation of an alpha, beta-unsaturated ketone: a novel xenobiotic biotransformation in mammals.
Reduction of an alpha, beta-unsaturated ketone to the corresponding saturated ketone in a 2-benzylidene-3-ketocoumaran derivative has been investigated. Reductase activity resides in the cytosolic fraction of liver, lung and kidney. Rat and human blood also contain significant reductase activity. Hepatic reductase activity was high in guinea-pigs followed by hamsters, rabbits, rats and mice. The substrate had an apparent Km and Vmax of 5.6 microM and 1.3 nmol/min per mg protein, respectively. The reduction was dependent upon NADPH having an apparent Km of 14.8 microM and a Vmax of 1.0 nmol/min per mg protein. Only the A side hydrogen of NADPH was incorporated into the reduced product. The reaction was inhibited by cyanide, and sulphydryl reagents. Phenobarbital did not induce the activity in rats.
D000818:Animals; D001572:Benzofurans / Q000378:metabolism*; D001711:Biotransformation; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D009132:Muscles / Q000201:enzymology; D009249:NADP / Q000494:pharmacology; D010088:Oxidoreductases / Q000097:blood / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D001572:Benzofurans; D009249:NADP; C040722:LY 140091; C040718:LY 171859; D010088:Oxidoreductases