Abstract
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exhibit genetic polymorphism and tissue specificity. ADH and ALDH isozyme phenotypes from 39 surgical Chinese lung specimens were identified by agarose isoelectric focusing. The identity of the lung β-ADHs was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation,K m values for NAD and ethanol, and inhibition by 4-methylpyrazole or 1,10-phenanthroline. The β2 allele, coding for β2 polypeptide, was found to be predominant in the lung specimens studied. The ADH activities in the lungs with the homozygous phenotype ADH2 2-2 (exhibiting β2β2) and ADH2 1-1 (exhibiting β1β1) and the heterozygous phenotype ADH2 2-1 (exhibiting β2β2, β2β1, and β1β1) were determined to be 999±77, 48±17, and 494±61 nmol/min/g tissue, respectively. Fifty-one percent of the specimens studied lacked the ALDH2 activity band on the isoelectric focusing gels. The activities in the lung tissues with the ALDH2-active phenotype and the inactive phenotype were determined to be 30±3 and 17±1 nmol/min/g tissue, respectively. These findings indicate that human pulmonary ethanol-metabolizing activities differ significantly with respect to genetic polymorphism at both theADH 2 and theALDH 2 loci. The results suggest that individuals with highV max β2-ADH and deficient in low-K m mitochondrial ALDH2, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during alcohol consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite.
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This work was supported by Grants NSC 77-0412-B016-58 and NSC 80-0412-B016-21 from the National Science Council, Republic of China.
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Yin, SJ., Liao, CS., Chen, CM. et al. Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: Implications for ethanol metabolism and cytotoxicity. Biochem Genet 30, 203–215 (1992). https://doi.org/10.1007/BF02399709
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DOI: https://doi.org/10.1007/BF02399709