Extremely high drug-reductase activity based on aldehyde oxidase in monkey liver.
Drug-reducing ability of monkey liver cytosol was examined in this study. Monkey liver cytosol exhibited significant reductase activities toward zonisamide, sulindac and imipramine N-oxide in the presence of 2-hydroxypyrimidine or benzaldehyde, an electron donor to aldehyde oxidase. These activities were abolished by inhibitors of aldehyde oxidase, such as menadione. These reductase activities in monkeys were extremely high compared to those in other animals. The zonisamide reductase activity of monkey liver cytosol was about 40-fold higher than that of the liver microsomes. It appears that the high levels of aldehyde oxidase exists in monkey liver, and zonisamide, sulindac and imipramine N-oxide are mainly reduced by this enzyme, not by cytochrome P450.
Kitamura
S
S
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan. kitamura@pharm.hiroshima-u.ac.jp
Ohashi KNK
Sugihara
K
K
Hosokawa
R
R
Akagawa
Y
Y
Ohta
S
S
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism; D006168:Guinea Pigs; D007099:Imipramine / Q000378:metabolism; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D000078305:Zonisamide
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D007555:Isoxazoles; D004364:Pharmaceutical Preparations; D000078305:Zonisamide; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase; D007099:Imipramine