Toshiyuki Higuchi
Kumamoto University
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Featured researches published by Toshiyuki Higuchi.
Biochimica et Biophysica Acta | 1993
Toshiyuki Higuchi; Yorishige Imamura; Masaki Otagiri
The kinetic mechanism for the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was investigated. The initial velocity and product inhibition studies indicated that the enzymatic reaction follows an ordered Bi Bi mechanism, in which NADPH binds to the enzyme first and NADP leaves last. This kinetic mechanism was confirmed on the basis of the dead-end inhibition by Cibacron Blue and the binding of NADPH and NADP to the free enzyme. However, whether or not coenzyme-induced isomerization is involved in the enzymatic reaction remains to be clarified. In kinetic studies of inhibition of the enzyme by therapeutically active drugs, indomethacin and befunolol were found to be noncompetitive and competitive inhibitors, respectively, with respect to acetohexamide.
Biochimica et Biophysica Acta | 1994
Toshiyuki Higuchi; Yorishige Imamura; Masaki Otagiri
Carbonyl reductase from rabbit kidney was inactivated by phenylglyoxal (PGO) and 2,4,6-trinitrobenzenesulfonate sodium (TNBS). NADP+ protected the enzyme from the inactivations by PGO and TNBS, suggesting that essential arginine and lysine residues are located in coenzyme-binding domain of the enzyme. Judging from the effects of PGO-treated enzymes in the presence and in the absence of NADP+ on the fluorescence intensity of NADPH, one essential arginine residue in coenzyme-binding domain was found to have a role in the binding of NADPH to the enzyme. Indomethacin afforded a significant protection against inactivation of the enzyme by PGO, whereas it could not protect the enzyme from the inactivation by TNBS. It is reasonable to postulate that indomethacin interacts at least in part with or near one essential arginine residue in coenzyme-binding domain of carbonyl reductase from rabbit kidney.
Journal of Enzyme Inhibition | 1997
Yorishige Imamura; Toshihisa Koga; Toshiyuki Higuchi; Masaki Otagiri; E. Sugino; S. Hibino
The reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was inhibited by befunolol, moperone, levobunolol, daunorubicin and loxoprofen, which have a ketone group within their chemical structures and are substrates for the enzyme. A significant correlation was observed between the common logarithm of Vmax/Km values of the enzyme for befunolol, moperone, levobunolol and daunorubicin and the percentage inhibition of the enzyme, confirming that these drugs are competitive substrates of the enzyme with respect to acetohexamide. However, the plot for loxoprofen, a nonsteroidal anti-inflammatory drug with a ketone group, was apparently distant from the regression line obtained. Although nonsteroidal anti-inflammatory drugs with a ketone group such as suprofen and fenbufen were not reduced by the enzyme, they strongly inhibited the reduction of acetohexamide catalyzed by the enzyme.
Journal of Enzyme Inhibition | 2001
Yorishige Imamura; Toshiyuki Higuchi; Masaki Otagiri
Suprofen (SF) was little reduced by rabbit kidney carbonyl reductase, whereas its methyl ester (SPM) was an efficient substrate of the enzyme. To account for the differential catalytic activities for SF and SPM, the protective effects of these compounds against the inactivation of the enzyme by phenylglyoxal (PGO) were compared. Since the carboxyl group of SP is negatively charged and one essential arginine residue is known to be located in the NADPH-binding site of the enzyme, the protection of SP against the inactivation of the enzyme by PGO is expected to be more effective than that of SPM lacking a carboxyl group. However, the protective effects of SP and SPM were very similar. These results suggest that in spite of evidence for the binding of SP to the coenzyme-binding site, the carboxyl group of SP fails to interact with one essential arginine residue located in the site.
Thrombosis and Haemostasis | 2000
Hidemi Ishii; Kimihiko Takada; Toshiyuki Higuchi; Junichi Sugiyama
Journal of pharmacobio-dynamics | 1989
Yorishige Imamura; Yuichiro Kojima; Toshiyuki Higuchi; Hiroyuki Akita; Takeshi Oishi; Masaki Otagiri
Bioorganic Chemistry | 1994
Yorishige Imamura; Toshiyuki Higuchi; Masaki Otagiri; Shinji Nagumo; H. Akita
Biological & Pharmaceutical Bulletin | 1995
Toshiyuki Higuchi; Yorishige Imamura; Masaki Otagiri
Iubmb Life | 1994
Toshiyuki Higuchi; Yorishige Imamura; Masaki Otagiri
Chemical & Pharmaceutical Bulletin | 1989
Yorishige Imamura; Toshiyuki Higuchi; Yuichiro Kojima; Masaki Otagiri