抄録
This minireview describes some physiological factors affecting the metabolic reduction of drugs having a ketone group and the properties of enzymes responsible for the metabolic reduction of these drugs. Acetohexamide and befunolol were chosen as model drugs having a ketone group. Species differences of acetohexamide reductase activity in the liver and kidney were observed among animals tested. The acetohexamide reductase activity in 10000xg supernatant of rat liver was higher in male than in female, and streptozotocin-induced diabetes caused a disappearance in the sex difference. Furthermore, befunolol reductase was purified to homogeneity from the cytosolic fraction of rabbit liver by various chromatographic techniques. On the basis of the substrate specificities and some properties, befunolol reductase was classified as a carbonyl reductase. The reduction of befunolol catalyzed by befunolol reductase proceeded in an ordered Bi Bi mechanism. These observations will provide a better understanding for the metabolic reduction of drugs having a ketone group. The role of the heart in acetohexamide reduction and the product stereoselectivity of acetohexamide reduction are also discussed.
