Abstract
The human alcohol dehydrogenase gene family consists of seven genes with distinct but overlapping patterns of expression. ADH enzymes metabolize a wide range of alcohols. Some of the ADH enzymes catalyze the first, rate-limiting step in the oxidative metabolism of ethanol. This pathway generates acetaldehyde as an intermediate, which in turn is oxidized by aldehyde dehydrogenase to acetate. Allelic differences in ADH2 and ADH3 genes encode forms of the enzymes that differ in their kinetic properties toward ethanol. These differences have been shown to affect the risk for alcoholism in Japanese and Chinese individuals (Thomasson et al. 1991; Thomasson et al. 1994; Thomasson et al. 1993; Crabb et al. 1995; Tanaka et al. 1996; Yamauchi et al. 1995; Maezawa et al. 1995; Tu and Israel, 1995). We hypothesize that differences in the expression of these genes could also affect the metabolism of ethanol, and thereby modify the risk for alcoholism in other populations.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Brown, C. J., Baltz, K. A. and Edenberg, H. J.: Expression of the human ADH2 gene: an unusual Spl-binding site in the promoter of a gene expressed at high levels in liver. Gene 121 (1992) 313–320.
Brown, C. J., Zhang, L. and Edenberg, H. J.: Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter. DNA Cell Biol. 13 (1994) 235–247.
Brown, C. J., Zhang, L. and Edenberg, H. J.: Gene expression in a young multigene family: tissue-specific differences in the expression of the human alcohol dehydrogenase genes ADH1, ADH2 and ADH3. DNA Cell Biol. 15 (1996) 187–196.
Carr, L. G. and Edenberg, H. J.: Cis-acting sequences involved in protein binding and in vitro transcription of the human alcohol dehydrogenase gene ADH2. J. Biol. Chem. 265 (1990) 1658–1664.
Cheung, B., Holmes, R. S. and Beacham, I. R.: Molecular evolution of class I alcohol dehydrogenases in primates: Models for gene evolution and comparisons of 3′ untranslated regions of cDNAs. Adv. Exp. Med. Biol. 372 (1995) 315–320.
Crabb, D. W., Edenberg, H. J., Thomasson, H. R. and Li, T.-K. in The Genetics of Alcoholism, H. Begleiter and B. Kissin, Eds. (Oxford Univ. Press, New York, 1995), p. 202.
Edenberg, H. J. and Brown, C. J.: Regulation of human alcohol dehydrogenase genes. Pharmacogenet. 2 (1992) 185–196.
Edenberg, H. J., Brown, C. J. and Zhang, L.: Regulation of the human alcohol dehydrogenase genes ADH1, ADH2 and ADH3: Differences in cis-acting sequences at CTF/NF-I sites. Adv. Exp. Med. Biol. 328 (1993) 561–570.
Edenberg, H. J., Brown, C. J. and Zhang, L.: Alcohol dehydrogenases: molecular biology and gene regulation. Alcohol. Alcohol. Suppl.2 (1995) 123–127.
Hur, M.-W. and Edenberg, H. J.: Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase. Gene 121 (1992) 305–311.
Hur, M.-W. and Edenberg, H. J.: Cell-specific function of cis-acting elements in the regulation of human alcohol dehydrogenase 5 gene expression and effect of the 5′-nontranslated region. J. Biol. Chem. 270 (1995) 9002–9009.
Jornvall, H., Danielsson, O., Hjelmqvist, L., Persson, B. and Shafqat, J.: The alcohol dehydrogenase system. Adv. Exp. Med. Biol. 372 (1995) 281–294.
Kedishvili, N. Y., Bosron, W. F., Stone, C. L., Hurley, T. D., Peggs, C. F., Thomasson, H. R., Popov, K. M., Carr, L. G., Edenberg, H. J. and Li, T.-K.: Expression and kinetic characterization of recombinant human stomach alcohol dehydrogenase: Active site amino acid sequence explains substrate specificity compared with liver isozymes. J. Biol. Chem. 270 (1995a) 3625–3630.
Kedishvili, N. Y., Bosron, W. F., Stone, C. L., Peggs, C. F., Thomasson, H. R., Popov, K. M., Carr, L. G., Hurley, T. D., Edenberg, H. J. and Li, T.-K.: Cloning and expression of a human stomach alcohol dehydrogenase isozyme. Adv. Exp. Med. Biol. 372 (1995b) 341–347.
Maezawa, Y., Yamauchi, M., Toda, G., Suzuki, H. and Sakurai, S.: Alcohol-metabolizing enzyme polymorphisms and alcoholism in Japan. Alcohol. Clin. Exp. Res. 19 (1995) 951–954.
Moreno, A. and Pares, X.: Purification and characterization of a new alcohol dehydrogenase from human stomach. J. Biol. Chem. 266 (1991) 1128–1133.
Satre, M. A., Zgombic-Knight, M. and Duester, G.: The complete structure of the human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene. J. Biol. Chem. 269 (1994) 15606–15612.
Stewart, M. J., McBride, M. S., Winter, L. A. and Duester, G.: Promoters for the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3: interaction of CCAAT/enhancer-binding protein with elements flanking the ADH2 TATA box. Gene. 90 (1990a) 271–279.
Stewart, M. J., Shean, M. L. and Duester, G.: Trans activation of human alcohol dehydrogenase gene expression in hepatoma cells by C/EBP molecules bound in a novel arrangement just 5′ and 3′ to the TATA box. Mol. Cell. Biol. 10 (1990b) 5007–5010.
Stewart, M. J., Shean, M. L., Paeper, B. W. and Duester, G.: The role of CCAAT/enhancer-binding protein in the differential transcriptional regulation of a family of human liver alcohol dehydrogenase genes. J. Biol. Chem. 266 (1991) 11594–11603.
Stone, C. L., Thomasson, H. R., Bosron, W. F. and Li, T.-K.: Purification and partial amino acid sequence of a high-activity human stomach alcohol dehydrogenase. Alcohol. Clin. Exp. Res. 17 (1993) 911–918.
Tanaka, F., Shiratori, Y., Yokosuka, O., Imazeki, F., Tsukada, Y. and Omata, M.: High incidence of ADH2*1/ALDH2*1 genes among Japanese alcohol dependents and patients with alcoholic liver disease. Hepatol. 23 (1996) 234–239.
Thomasson, H. R., Edenberg, H. J., Crabb, D. W., Mai, X. L., Jerome, R. E., Li, T. K., Wang, S. P., Lin, Y. T., Lu, R. B. and Yin, S. J.: Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am. J. Hum. Genet. 48 (1991) 677–681.
Thomasson, H. R., Crabb, D. W., Edenberg, H. J. and Li, T.-K.: Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behavior Genetics 23 (1993) 131–136.
Thomasson, H. R., Crabb, D. W., Edenberg, H. J., Li, T.-K., Hwu, H.-G., Chen, C. C., Yeh, E. K. and Yin, S.-J.: Low frequency of the ADH2*2 allele among Atayal natives of Taiwan with alcohol use disorders. Alcohol. Clin. Exp. Res. 18 (1994) 640–643.
Tu, G.-C. and Israel, Y.: Alcohol consumption by Orientals in North America is predicted largely by a single gene. Behavior Genetics 25 (1995) 59–65.
Yamauchi, M., Maezawa, Y., Toda, G., Suzuki, H. and Sakurai, S.: Association of a restriction fragment length polymorphism in the alcohol dehydrogenase 2 gene with Japanese alcoholic liver cirrhosis. J. Hepatology 23 (1995) 519–523.
Yang, Z.-N., Davis, G. J., Hurley, T. D., Stone, C. L., Li, T.-K. and Bosron, W. F.: Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction. Alcohol. Clin. Exp. Res. 18 (1994) 587–591.
Yasunami, M., Chen, C. S. and Yoshida, A.: A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme. Proc. Natl. Acad. Sci. USA 88 (1991) 7610–7614.
Yin, S.-J., Wang, M.-F., Liao, C.-S., Chen, C.-M. and Wu, C.-W.: Identification of a human stomach alcohol dehydrogenase with distinctive kinetic properties. Biochem. Int. 22 (1990) 829–835.
Yin, S.-J., Chou, F.-J., Chao, S.-F., Tsai, S.-F., Liao, C.-S., Wang, S.-L., Wu, C.-W. and Lee, S.-C.: Alcohol and aldehyde dehydrogenases in human esophagus: comparison with the stomach enzyme activities. Alcohol. Clin. Exp. Res. 17 (1993) 376–381.
Yokoyama, S., Matsuo, Y., Ramsbotham, R. and Yokoyama, R.: Molecular characterization of a class IV human alcohol dehydrogenase gene (ADH7). FEBS Lett. 351 (1994) 411–415.
Zgombic-Knight, M., Foglio, M. H. and Duester, G.: Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro. J. Biol. Chem. 270 (1995) 4305–4311.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer Science+Business Media New York
About this chapter
Cite this chapter
Edenberg, H.J. et al. (1996). Regulation of the Seven Human Alcohol Dehydrogenase Genes. In: Weiner, H., Lindahl, R., Crabb, D.W., Flynn, T.G. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 6. Advances in Experimental Medicine and Biology, vol 414. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5871-2_39
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5871-2_39
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7692-7
Online ISBN: 978-1-4615-5871-2
eBook Packages: Springer Book Archive