CONTRIBUTION OF ACIDIC ADH(CLASS III) TO ALCHOL METABOLISM

酸性 ADH（III 类）对酒精代谢的贡献

基本信息

批准号：
04454231
负责人：
HASEBA Takeshi
金额：
$ 0.64万
依托单位：
NIPPON MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454231/
关键词：
Mouse Alcohol dehydrogenase Class I ADH Class III ADH Solution hydrophobicity Activity regulation Alcohol metabolism Intracellular hydrophobicity ClassIおよびIIIADH 疎水物質マイクロダイアリシス法

项目摘要

(1) A fraction of acidic alcohol dehydrogenase (Class III ADH) activity of the mouse liver corresponded to 10-42% that of basic ADH (Class I) known as a key enzyme in alcohol metabolism in vivo, when ethanol was used as a substrate at concentrations of blood level (15-100 mM).(2) The activity of acidic ADH was enhanced with the increase in hydrophobicity of the reaction solution. This activation was due to a marked increase of the catalytic efficiency (Kcat/Km), based on a marked decrease of the Km for ethanol. On the other had, the activity of basic ADH was strongly depressed with the increase in the solution hydrophobicity.(3) Acidic ADH was found to localize mainly in the sinusoidal endothelial cells of the mouse liver, whereas basic ADH was shown to distribute within the cytoplasmic matrix of hepatocytes. Staining the liver tissues with a hydrophobic probe (Nile red) showed that the cytoplasm was hydrophobic, and moreover, the intracelluar hydrophobicity was higher in the sinusoida … More l cells than in the parenchymal cells. These results suggest that intracellular acidic ADH activity was highted, whereas the basic ADH activity was lowered by the effects of intracellular hydrophobicity, compared with their activities measured by the conventional in vitro method.(4) Class III ADH was found in the liver of a so-called "ADH^-" deermouse that possessed a capacity of alcohol metabolism more than 50% that of a "ADH^+" strain. A class of ADH which "ADH^-" strain was genetically deficient in was identified as class I.(5) The contributions of basic ADH and catalase to the total alcohol metabolism in the mouse were estimated to be about 50% and 20%, respectively, by additional administration of specific inhibitors (capronamide for basic ADH and aminotriazole for catalase) after ethanol administration at a dose of 3.0 g/kg (i. p.). The total metabolism was almost completely depressed by adminstration of 4-methylpyrazole, which inhibited not only class I ADH, but also class III ADH and catalase pathway. Taken together with the results from in vitro studies, the alcohol metabolism accounting for about 30% of the total one, which was independent to class I ADH and catalase, was suggested to be due to acidic ADH.Thus, it was concluded that acidic ADH (Class III) may play an important role in alcohol metabolism in vivo and the contributions of the two major ADHs (Class I and III) to the metabolism were reversely regulated in response to the intracellular hydrophobicity. Less

（1）小鼠的一部分酸性酒精脱氢酶（III ADH）的活性对应于体内酒精代谢中基本ADH（I类）键酶的10-42％，当血液水平（15-100毫米）。溶液的增加，基本ADH的活性很大）表明细胞质是疏水性的，此外，正弦曲线中的燃烧性毛毛比在实质细胞中更多的L L细胞。在所谓的“ ADH^”的肝脏中发现了常规的体外方法，该肝脏具有酒精中毒的含量超过“ ADH^”的50％以上遗传上的缺陷被视为I级。通过对特定抑制剂的额外施用（碱性ADH的capronamide和氨基酸氨基曲酶）的4-甲基吡喃酶，这是4-甲基吡唑的额外施用。同样，Classo Classo III ADH和过氧化氢酶途径与体外代谢的结果一起占AVOUT的30％（独立于ADH和CETALASE），这是由于酸性ADH所致。酸性ADH（III级）可能在体内酒精代谢中起重要作用，并且两个主要的ADH（I级和III）的贡献对响应细胞内水物的响应较小。