MOLECULAR ABNORMALITY OF AN INACTIVE ALDEHYDE DEHYDROGENASE VARIANT COMMONLY FOUND IN ORIENTALS
MOLECULAR ABNORMALITY OF AN INACTIVE ALDEHYDE DEHYDROGENASE VARIANT COMMONLY FOUND IN ORIENTALS
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DOI：
10.1073/pnas.81.1.258
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
IKAWA, M
中科院分区：
文献类型：
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作者：
YOSHIDA, A;HUANG, IY;IKAWA, M
人的肝脏含有2种主要的醛脱氢酶[（ALDH）醛：NAD+氧化还原酶]同工酶，即，胞质ALDH 1组分和线粒体ALDH 2组分。50%的东方人是非典型的，只有ALDH 1同工酶，而缺少ALDH 2同工酶。非典型肝脏含有与ALDH 2组分相对应的无酶活性但免疫交叉反应性物质（CRM）。从正常肝脏中获得的具有酶活性的ALDH 2和从非典型肝脏中获得的CRM被还原，S-羧甲基化，并被胰蛋白酶消化。通过高效反相色谱和二维纸层析及电泳分析，发现ALDH 2的氨基酸序列为-Glu-Leu-Gly-Glu-Ala-Gly-Leu-Gln-Ala-Asn-Val-Gln-Val-Lys-，且CRM中与Lys相邻的Gln被Lys取代。所有其他胰蛋白酶肽，包括8个含有S-羧甲基半胱氨酸的肽，在ALDH 2和CRM中是常见的。人ALDH 2基因座中的点突变产生Gln →。赖氨酸取代和酶失活。
Usual human livers contain 2 major aldehyde dehydrogenase [(ALDH) aldehyde:NAD+ oxidoreductase] isozymes.sbd.i.e., a cytosolic ALDH1 component and a mitochondrial ALDH2 component.sbd.whereas .apprxeq. 50% of Orientals are atypical and have only the ALDH1 isozyme and are missing the ALDH2 isozyme. Atypical livers contain an enzymatically inactive but immunologically crossreactive material (CRM) corresponding to the ALDH2 component. The enzymatically active ALDH2 obtained from a usual liver and the CRM obtained from an atypical liver were reduced, S-carboxymethylated, and digested by trypsin. Separation of their digests by high-performance reverse-phase chromatography and by 2-dimensional paper chromatography and electrophoresis revealed that ALDH2 contained a peptide sequence of -Glu-Leu-Gly-Glu-Ala-Gly-Leu-Gln-Ala-Asn-Val-Gln-Val-Lys- and that the Gln adjacent to Lys was substituted by Lys in CRM. All other tryptic peptides, including 8 peptides containing S-carboxymethylcysteine, were common in ALDH2 and CRM. A point mutation in the human ALDH2 locus produced the Gln .fwdarw. Lys substitution and enzyme inactivation.