Human stomach alcohol and aldehyde dehydrogenases (ALDH): A genetic model proposed for ALDH III isozymes |
| |
Authors: | S -J Yin T -C Cheng C -P Chang Y -J Chen Y -C Chao H -S Tang T -M Chang C -W Wu |
| |
Institution: | (1) Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China;(2) Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China;(3) Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China;(4) Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China;(5) Department of Surgery, Veterans General Hospital, Taipei, Taiwan, Republic of China |
| |
Abstract: | 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. γγ ADH isozymes
were expressed predominantly in the mucosal layer of the stomach, whereas ββ 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 allelesADH
3
1
andADH
3
2
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 exhibitedK
m values in the millimolar range for propionaldehyde atpH 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,ALDH
3a andALDH
3b, with theALDH
3b 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 forALDH
3b
1
andALDH
3b
2
were calculated to be 0.14 and 0.86, respectively. Several lines of biochemical evidence consistent with this genetic model
are discussed.
This work was supported by grants from the National Science Council, Republic of China, and the Institute of Biomedical Sciences,
Academia Sinica. |
| |
Keywords: | alcohol dehydrogenase aldehyde dehydrogenase genetic model human stomach isozyme |
本文献已被 SpringerLink 等数据库收录! |
|