caa a22 4500 397557582 CHVBK 20180308164807.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021291 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021291 Purification and Catalytic Properties of a Novel Acetohexamide-Reducing Enzyme from Rabbit Heart [Elektronische Daten] [Yorishige Imamura, Akio Ryu, Toshihisa Koga, Toshiyuki Higuchi, Masaki Otagiri, Masako Nozawa, Hiroyuki Akita] An enzyme catalyzing the metabolic reduction of acetohexamide [4-acetyl-N-(cyclohexyl-carbamoyl)benzenesulfonamide], an oral antidiabetic drug, was purified to homogeneity from the cytosolic fraction of rabbit heart. The molecular mass of the purified enzyme was estimated to be 110 kDa by gel filtration and nondenaturing PAGE and 28kDa by SDS-PAGE, suggesting that the enzyme is composed of four identical-size subunits. 4-Benzoyl-pyridine and p-nitroacetophenone, typical substrates of carbonyl reductase [EC 1.1.1.184], were not reduced by the enzyme. Of drugs with a ketone group tested, only acetohexamide was a good substrate of the enzyme. The enzyme effectively reduced analogs substituted with various alkyl groups instead of the cyclohexyl group in acetohexamide, although it had little or no ability to reduce analogs substituted with various alkyl groups instead of the methyl group in acetohexamide. The enzyme was inhibited not only by quercetin, a well-known inhibitor of carbonyl reductase, but also by phenobarbital, a potent inhibitor of aldehyde reductase [EC 1.1.1.2]. These results indicate that the enzyme purified from rabbit heart is a novel enzyme responsible for the reduction of acetohexamide and its analogs. © by the Journal of Biochemistry Regular Papers nationallicence acetohexamide analog nationallicence acetohexamide-reducing enzyme nationallicence drug metabolism nationallicence rabbit heart nationallicence tetrameric enzyme nationallicence Imamura Yorishige Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut Ryu Akio Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut Koga Toshihisa Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut Higuchi Toshiyuki Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut Nozawa Masako School of Pharmaceutical Sciences, Toho University 2-2-1 Miyama, Funabashi, Chiba 274 aut Akita Hiroyuki School of Pharmaceutical Sciences, Toho University 2-2-1 Miyama, Funabashi, Chiba 274 aut The Journal of Biochemistry Oxford University Press 119/4(1996-04), 648-652 0021-924X 119:4<648 1996 119 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021291 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021291 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Imamura Yorishige Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut NATIONALLICENCE 700 1- Ryu Akio Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut NATIONALLICENCE 700 1- Koga Toshihisa Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut NATIONALLICENCE 700 1- Higuchi Toshiyuki Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut NATIONALLICENCE 700 1- Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University 5-1 Oehonmachi, Kumamoto 862 aut NATIONALLICENCE 700 1- Nozawa Masako School of Pharmaceutical Sciences, Toho University 2-2-1 Miyama, Funabashi, Chiba 274 aut NATIONALLICENCE 700 1- Akita Hiroyuki School of Pharmaceutical Sciences, Toho University 2-2-1 Miyama, Funabashi, Chiba 274 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 119/4(1996-04), 648-652 0021-924X 119:4<648 1996 119 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford