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Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.

Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Research Abstract Details 

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  • Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Abstract Text:

    y imamuraY Imamura,t kogaT Koga,t migitaT Migita,a ryuA Ryu,m otagiriM Otagiri,m nozawaM Nozawa,h akitaH Akita,

    The structural requirements of acetohexamide reductases purified from rabbit liver, kidney, and heart for substrates and inhibitors were examined. Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it with various alkyl groups instead of the cyclohexyl group were used as substrates for these three enzymes. The results obtained as to substrate specificity suggested that the nature of the substrate-binding region of the heart enzyme is markedly different from those of the substrate-binding regions of the liver and kidney enzymes. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by tolbutamide was competitive with respect to acetohexamide and uncompetitive with respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl groups instead of the n-butyl group exhibited very pronounced inhibition of only the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme, unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature near its substrate-binding region, and that this hydrophobic cleft plays a critical role in the interaction of the heart enzyme with the cyclohexyl group of acetohexamide.

    Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Publishing Authors By Initials

    y imamuraY Imamura,t kogaT Koga,t migitaT Migita,a ryuA Ryu,m otagiriM Otagiri,m nozawaM Nozawa,h akitaH Akita,

    For similar heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research

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    Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Journal of biochemistry

    VOLUME: 121

    Page Numbers: 705-10

    Journal Abbreviation: J. Biochem.

    ISSN: 0021-924X

    DAY: 19

    MONTH: Apr

    YEAR: 1997

    Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 376600

    Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Keywords Mesh Terms:

    KEYWORDS: Triazines

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors. Information

    Substance Name: acetohexamide reductase

    Registry Number: EC 1.1.1.-

    Grant and Affiliation Information for Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.

    AFFILIATION: Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi.

    Country: JAPAN

    JAPAN Research PublicationJAPAN Research Publication

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    MEDLINETA: J Biochem

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