New molecular forms of human liver alcohol dehydrogenase: isolation and characterization of ADHIndianapolis.
New molecular forms of human liver alcohol dehydrogenase: isolation and characterization of ADHIndianapolis.
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人肝乙醇脱氢酶的新分子形式：ADH印第安纳波利斯的分离和表征。
DOI：
10.1073/pnas.77.10.5784
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发表时间：
1980
影响因子：
11.1
通讯作者：
Vallee,BL
中科院分区：
文献类型：
--
作者：
Bosron,WF;Li,TK;Vallee,BL
酒精中毒的生物化学决定因素和人类对酒精反应的变异性的遗传相关性直到最近才变得模糊。鉴定具有不同催化性质的遗传决定的醇脱氢酶同工酶可能对这个问题有重要意义。最近在来自印第安纳州印第安纳波利斯的城市人群的16%的肝脏样本中鉴定了人肝脏乙醇脱氢酶（ADH;酒精：NAD+氧化还原酶，EC 1.1.1.1）的新分子形式[Bosron，W. F.、李，T- K. & Vallee，B. L.（1979）Biochem. Biophys.通信资源91，1549-1555]。这些样品的区别特征是（i）它们在pH 7.0和10.0下均显示出乙醇氧化的最佳活性，以及（ii）它们形成β β同工酶阴极的电泳带。从这样的肝脏中，现在已经分离出三种新的ADH形式，其中一种具有单一的最适pH 7.0，其中两种具有双重最适pH 7.0和10.0。这些新形式分别被指定为ADH印第安纳波利斯形式1、2和3。它们可以通过其电泳迁移率、最适pH和乙醇Km（pH 7.5时约60 mM）与先前描述的ADH同工酶（包括所谓的“非典型”同工酶）区分。根据含有ADH Indianapolis的肝脏的电泳模式和三种分离分子形式的流动性，ADH Indianapolis可能是ADH 2基因位点多态性的结果，该基因位点编码β亚基。
The biochemical determinants of alcoholism and genetic correlates for the variability in man's response to alcohol have remained obscure until recently. The identification of genetically determined isoenzymes of alcohol dehydrogenase with different catalytic properties may bear importantly upon this problem. New molecular forms of human liver alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) have recently been identified in 16% of the liver specimens from an urban population from Indianapolis, Indiana [Bosron, W. F., Li, T.-K. & Vallee, B. L. (1979) Biochem. Biophys. Res. Commun. 91, 1549-1555]. The distinguishing features of these specimens were (i) they showed activity optima for ethanol oxidation at both pH 7.0 and 10.0 and (ii) they formed electrophoretic bands cathodic to the beta beta isoenzyme. From such livers, three new ADH forms have now been isolated, one of which has a single pH optimum at 7.0 and two of which have dual optima at pH 7.0 and 10.0. These new forms were designated ADHIndianapolis forms 1,2, and 3, respectively. They can be differentiated from previously described ADH isoenzymes, including the so-called "atypical" isoenzyme, by their electrophoretic mobility, pH optima, and Km for ethanol (approximately 60 mM at pH 7.5). Based upon the electrophoretic pattern of livers containing ADHIndianapolis and the mobility of the three isolated molecular forms, ADHIndianapolis may be the result of polymorphism at the ADH2 gene locus, which codes for the beta subunit.