Inhibition of Human Aldehyde Reductase by Drugs for Testing the Function of Liver and Kidney

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概要

• 論文の詳細を見る

• Drugs for testing the function of liver and kidney (sulfobromophthalein, phenolsulfonphthalein, indigo carmine and indocyanine green) and other organic anions (rose bengal and haematin) were found to potently inhibit human liver aldehyde reductase that is involved in the detoxification of 3-deoxyglucosone and methylglyoxal, reactive intermediates, during the formation of advanced glycation end products. The inhibition patterns by the compounds were non-competitive with respect to both coenzyme (NADPH) and substrate (D-glucuronate). The kinetics of the inhibition by a mixture of the 2 inhibitors suggests that all the inhibitory compounds bind to overlapping sites on the enzyme. The binding of rose bengal, sulfobromophthalein and phenylsulfonphthalein to the free enzyme was detected by ultrafiltration assay. However, in the reverse reaction, the enzyme was inhibited competitively with respect to the alcohol substrate by rose bengal, haematin, phenolsulfonphthalein, sulfobromophthalein, indigo carmine and indocyanine green, which showed K_i values of 0.1,1,3,4,4 and 10 μM, respectively. The results suggest that these potent inhibitors bind weakly to the free enzyme and tightly to the enzyme-NADP binary complex.

• 社団法人日本薬学会の論文
• 1999-07-15

著者

• SHINTANI Syunichi

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• Ishikura S

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Ishikura Shuhei

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Ishikura Syuhei

  Hospital For Sick Children

• SHINODA Michio

  Chunou Hospital

• MORI Shinichi

  Chunou Hospital

• SHINTANI Syunichi

  Gifu Prefectural Hospital

• ISHIKURA Syuhei

  Gifu Pharmaceutical University

• HARA Akira

  Gifu Pharmaceutical University

• Hara Akira

  Lab. Of Biochemistry Gifu Pharmaceutical Univ.

• Hirakawa Akiha

  3rd Dept. Of Intern. Med. Kyoto Univ.

• Shintani Syunichi

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Hara Akira

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Hara Akira

  From The Third Division Department Of Internal Medicine Kyoto University

• Hara Akira

  Department Of Pathology Gifu University School Of Medicine

• Hirakawa Akina

  3rd Medical Clinic Faculty Of Medicine Kyoto University

• Shintani Syunichi

  Laboratory Of Biochemistry Gifu Parmaceutical University

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