Yin S J, Cheng T C, Chang C P, Chen Y J, Chao Y C, Tang H S, Chang T M, Wu C W
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Biochem Genet. 1988 Jun;26(5-6):343-60. doi: 10.1007/BF02401788.
Isozyme phenotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from human gastroendoscopic as well as surgical gastric biopsies were determined by starch gel electrophoresis and agarose isoelectric focusing. gamma gamma ADH isozymes were expressed predominantly in the mucosal layer of the stomach, whereas beta beta isozymes were in the muscular layer. In the 56 gastroendoscopic mucosal biopsies examined, the homozygous ADH3 1-1 phenotype was found in 75% of the samples, and the heterozygous ADH3 2-1 phenotype in 25%. Accordingly, the gene frequencies of the alleles ADH1/3 and ADH2/3 were calculated to be 0.88 and 0.12, respectively. Using a modified agarose isoelectric focusing procedure, gastric ALDH I, ALDH II, and up to five ALDH III forms could be clearly resolved. The ALDH III isozymes accounted for more than 80% of the total ALDH activities in gastric mucosa and exhibited Km values in the millimolar range for propionaldehyde at pH 9.0. Forty-five percent of the 55 gastroendoscopic biopsies studied lacked ALDH I isozyme. The complex gastric ALDH III isozyme phenotypes seen in these biopsies fall into three patterns. They can be interpreted by a genetic hypothesis, based on a dimeric molecule, in which there are two separate genes, ALDH3a and ALDH3b, with the ALDH3b locus exhibiting polymorphism. The homozygous phenotypes ALDH3b 1-1 and ALDH3b 2-2 were found to be 4 and 76%, respectively, and the heterozygous ALDH3b 2-1 phenotype 20%, of the total. Therefore, the allele frequencies for ALDH1/3b and ALDH2/3b were calculated to be 0.14 and 0.86, respectively. Several lines of biochemical evidence consistent with this genetic model are discussed.
通过淀粉凝胶电泳和琼脂糖等电聚焦法，测定了取自人胃镜检查以及手术获得的胃活检组织中乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）的同工酶表型。γγADH同工酶主要在胃黏膜层表达，而ββ同工酶则在肌层表达。在所检查的56份胃镜黏膜活检样本中，75%的样本呈现纯合子ADH3 1-1表型，25%的样本为杂合子ADH3 2-1表型。据此，计算出等位基因ADH1/3和ADH2/3的基因频率分别为0.88和0.12。采用改良的琼脂糖等电聚焦方法，可清晰分辨出胃ALDH I、ALDH II以及多达五种ALDH III形式。ALDH III同工酶占胃黏膜中总ALDH活性的80%以上，在pH 9.0时对丙醛的Km值处于毫摩尔范围。在所研究的55份胃镜活检样本中，45%缺乏ALDH I同工酶。在这些活检样本中观察到的复杂胃ALDH III同工酶表型可分为三种模式。基于二聚体分子的遗传假说可以对其进行解释，其中存在两个独立的基因，即ALDH3a和ALDH3b，ALDH3b位点表现出多态性。发现纯合子表型ALDH3b 1-1和ALDH3b 2-2分别占总数的4%和76%，杂合子ALDH3b 2-1表型占20%。因此，计算出ALDH1/3b和ALDH2/3b的等位基因频率分别为0.14和0.86。文中讨论了几条与该遗传模型相符的生化证据。
