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:
- 金额:$ 0.64万
- 依托单位:
- 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:
- 关键词:
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)小鼠肝脏的一部分酸性醇脱氢酶(III ADH)的活性与10-42%相对应为10-42%的基本ADH(I类),当时在体内被称为酒精代谢的关键酶,当时乙醇在血液水平的浓度(15-100 mm)中用作乙醇(15-100 mm)。(2)酸ADH的活性增强了酸性的活性。这种激活是由于催化效率明显提高(KCAT/km),这是基于乙醇的Km明显下降而引起的。另一方面,随着溶液疏水性的增加,碱性ADH的活性严重降低。(3)发现酸性ADH主要位于小鼠肝脏的正弦内皮细胞中,而基本ADH则显示出在肝素的细胞质基质中分布。用疏水性探针(尼罗河红)染色肝组织表明细胞质是疏水性的,此外,正弦曲线的细胞内疏水性高……L细胞比副群细胞中的L细胞多。这些结果表明,与传统的体外方法测量的其活性相比,细胞内酸性ADH活性被降低,而基本的ADH活性降低了。(4)在所谓的ADH^ - “ Deermouse”中具有比50%的ADH^ - aDH^ - aDH^ - aDH^ - aDH^ - a adh^ - 50%的植物的肝脏。 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。)。 4-甲基吡唑的守卫不仅抑制了I级ADH,而且还抑制了III级ADH和过氧化氢酶途径,几乎完全抑制了总代谢。与体外研究的结果一起,占含量与I级ADH和过氧化氢酶无关的酒精代谢约为酸性ADH。到细胞内疏水性。较少的
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Haseba, T., Yamamoto, I., Ohono, Y.and Uedaira, H.: "Effect of hydrophobicity of organic compounds on activities of alcohol dehydrogenase isozymes (Class I and III)." Proceedings of 6th Eur. Cong. Biotec.vol.III. WE066 (1993)
Haseba, T.、Yamamoto, I.、Ohono, Y. 和 Uedaira, H.:“有机化合物的疏水性对乙醇脱氢酶同工酶(I 类和 III 类)活性的影响”。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yamamoto, I., Haseba, T., Kurosu, M.and Watanabe, T.: "Allosterism of acidic alcohol dehydrogenase (Class III) of mouse liver and its role in alcohol metabolism." J.Nippon Med. Sch.59(2). 38-46 (1992)
Yamamoto, I.、Haseba, T.、Kurosu, M. 和 Watanabe, T.:“小鼠肝脏酸性乙醇脱氢酶(III 类)的变构及其在酒精代谢中的作用。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
山本伊佐夫: "マウスAcidic alcohol dehydrogenase(Class III)蛋白の活性調節とそのアルコール代謝における意義" 日本医大誌. 59(2). 38-46 (1992)
Isao Yamamoto:“小鼠酸性乙醇脱氢酶(III 类)蛋白的活性调节及其在酒精代谢中的意义”,日本医科大学杂志 59(2)(1992)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Haseba,Takeshi: "Effects of hydrophobicity of organic compounds on activities of alcohol dehydrogenase isozymes." Proceedings of 6th European Congress on Biotechnology.Vol III. WE066- (1993)
Haseba,Takeshi:“有机化合物的疏水性对乙醇脱氢酶同工酶活性的影响。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Haseba,Takeshi: "Effects of hydrophobicity of organic compounds on activities of alcohol dehydrogenase isozymes(Class I and III)." Proceedings of 6th European Congress on Biotechnology.Vol III. WE066 (1993)
Haseba,Takeshi:“有机化合物的疏水性对乙醇脱氢酶同工酶(I 类和 III 类)活性的影响。”
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- 发表时间:
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- 影响因子:0
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HASEBA Takeshi其他文献
HASEBA Takeshi的其他文献
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{{ truncateString('HASEBA Takeshi', 18)}}的其他基金
Roles of Class III ADH (ADH3), a new alcohol metabolizing enzyme, on biosensitivities for alcohol
III 类 ADH (ADH3)(一种新型酒精代谢酶)对酒精生物敏感性的作用
- 批准号:
20590689 - 财政年份:2008
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
ROLE OF CLASS III ALCOHOL DEHYDROGENASE (ADH3), A HOUSEKEEPING ENZYME FOR CYTOTOXICITY, IN ALCOHOL METABOLISM -IN VIVO STUDY USING KNOCKOUT MICE AND INVITRO STUDY ON ENZYME REGULATION-
III 类酒精脱氢酶 (ADH3)(一种细胞毒性管家酶)在酒精代谢中的作用 - 使用敲除小鼠的体内研究和酶调节的体外研究 -
- 批准号:
11470120 - 财政年份:1999
- 资助金额:
$ 0.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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