Skip to main content
SpringerLink
Log in
Book cover

Toward a Molecular Basis of Alcohol Use and Abuse pp 279–290Cite as

Retinoids and the alcohol dehydrogenase gene family

  • Chapter

Part of the book series: Experientia ((EXS,volume 71))

Summary

Alcohol dehydrogenase (ADH) is best known as the enzyme which catalyzes the reversible oxidation/reduction of ethanol/acetaldehyde. However, mammalian ADH has also been shown to function in vitro as a retinol dehydrogenase in the conversion of retinol (vitamin A alcohol) to retinoic acid, a hormone which regulates gene expression at the transcriptional level. It is clear that retinol must be converted to more active retinoid forms in order to fulfill its roles in growth, development, and cellular differentiation. An important unsolved issue in retinoid research is the control of retinoic acid synthesis from retinol during differentiation. Several enzymes which participate in the conversion of retinol to retinoic acid in vitro have been isolated, but more information on their relative importance is needed.

Human ADH exists as a family of isozymes encoded by seven genes which are differentially expressed in adult and fetal mammalian tissues, being found preferentially in the epithelial cells which are known to synthesize and respond to retinoic acid. Retinoic acid is also known to play a role in neural tube development in vertebrate embryos. Excessive doses of retinoic acid or ethanol are both teratogenic for neural tube development. A relationship may exist between these two types of teratogenesis due to the role of ADH in both retinol and ethanol metabolism and the ability of ethanol to competitively inhibit retinol oxidation. There is a lack of information on the expression patterns of ADH genes in early embryos, but transgenic mouse studies are presented here which show that the human ADH3 gene can be expressed in several mouse embryonic tissues including the neural tube. Thus, ethanol-induced neural tube defects seen in cases of fetal alcohol syndrome may be due to ethanol inhibition of retinol oxidation catalyzed by an embryonic ADH. This could potentially lower retinoic acid levels in the neural tube to the extent that gene expression is not properly regulated, resulting in morphological defects.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bühler, R., Pestalozzi, D., Hess, M. and von Wartburg, J.-P. (1983) Immunohistochemical localization of alcohol dehydrogenase in human kidney, endocrine organs and brain. Pharmacol. Biochem. Behay. 18: Supp1. 1, 55–59.

    Google Scholar 

  • Duester, G. (1991) A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step. Alcohol. Clin. Exp. Res. 15: 568–572.

    Article  PubMed  CAS  Google Scholar 

  • Duester, G., Shean, M.L., McBride, M.S. and Stewart, M.J. (1991) Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: Implications for regulation of retinoic acid synthesis. Mol. Cell. Biol. 11: 1638–1646.

    PubMed  CAS  Google Scholar 

  • Duester, G., Smith, M., Bilanchone, V. and Hatfield, G.W. (1986) Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the ß subunit. J. Biol. Chem. 261: 2027–2033.

    PubMed  CAS  Google Scholar 

  • Henehan, G.T.M. and Oppenheimer, N.J. (1993) Horse liver alcohol dehydrogenasecatalyzed oxidation of aldehydes: Dismutation precedes net production of reduced nicotinamide adenine dinucleotide. Biochemistry 32: 735–738.

    Article  PubMed  CAS  Google Scholar 

  • Hogan, B., Costantini, F. and Lacy, E. (1986) Manipulating the Mouse Embryo. Cold Spring Harbor Laboratory, Cold Spring Harbor.

    Google Scholar 

  • Hunter, K., Maden, M., Summerbell, D., Eriksson, U. and Holder, N. (1991) Retinoic acid stimulates neurite outgrowth in the amphibian spinal cord. Proc. Natl. Acad. Sci. USA 88: 3666–3670.

    Article  PubMed  CAS  Google Scholar 

  • Jones, K.L. and Smith, D.W. (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet 2: 999–1001.

    Article  Google Scholar 

  • Julià, P., Fanés, J. and Parés, X. (1986) Ocular alcohol dehydrogenase in the rat: Regional distribution and kinetics of the ADH-1 isoenzyme with retinol and retinal. Exp. Eye Res. 42: 305–314.

    Article  PubMed  Google Scholar 

  • Kim, C.-I., Leo, M.A. and Lieber, C.S. (1992) Retinol forms retinoic acid via retinal. Arch. Biochem. Biophys. 294: 388–393.

    Article  PubMed  CAS  Google Scholar 

  • Lammer, G.J., Chen, D.T., Hoar, R.M., Agnish, N.D., Benke, P.J., Braun, J.T., Curry, C. J., Femhoff, P.M., Grix, A.W., Lott, I.T., Richard, J.M. and Sun, S.C. (1985) Retinoic acid embryopathy. N. Engl. J. Med. 313: 837–841.

    Article  PubMed  CAS  Google Scholar 

  • Lee, M.-O., Manthey, C.L. and Sladek, N.E. (1991) Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. Biochem. Pharmacol. 42: 1279–1285.

    Article  PubMed  CAS  Google Scholar 

  • Lindblad, B. and Olsson, R. (1976) Unusually high levels of blood alcohol? JAMA 236: 1600–1602.

    Article  PubMed  CAS  Google Scholar 

  • Maden, M., Ong, D.E. and Chytil, F. (1990) Retinoid-binding protein distribution in the developing mammalian nervous system. Development 109: 75–80.

    PubMed  CAS  Google Scholar 

  • Mendelsohn, C., Ruberte, E., LeMeur, M., Morriss-Kay, G. and Chambon, P. (1991) Developmental analysis of the retinoic acid-inducible RAR-b2 promoter in transgenic animals. Development 113: 723–734.

    PubMed  CAS  Google Scholar 

  • Mezey, E. and Holt, P.R. (1971) The inhibitory effect of ethanol on retinol oxidation by human liver and cattle retina. Exp. Mol. Pathol. 15: 148–156.

    Article  PubMed  CAS  Google Scholar 

  • Moreno, A. and Parés, X. (1991) Purification and characterization of a new alcohol dehydrogenase from human stomach. J. Biol. Chem. 266: 1128–1133.

    PubMed  CAS  Google Scholar 

  • Parés, X., Cederlund, E., Moreno, A., Saubi, N., Höög, J.-O. and Jörnvall, H. (1992) Class IV alcohol dehydrogenase (the gastric enzyme): structural analysis of human aa-ADH reveals class IV to be variable and confirms the presence of a fifth mammalian alcohol dehydrogenase class. FEBS Lett. 303: 69–72.

    Article  PubMed  Google Scholar 

  • Petkovich, M., Brand, N.J., Krust, A. and Chambon, P. (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330: 444–450.

    Article  PubMed  CAS  Google Scholar 

  • Pietruszko, R. (1979) Nonethanol substrates of alcohol dehydrogenase. In: Majchrowicz, E. and Noble, E.P. (eds.): Biochemistry and Pharmacology of Ethanol, Vol. 1, Plenum Press, New York, pp. 87–106.

    Google Scholar 

  • Pocker, Y. and Li, H. (1993) The catalytic specificity of liver alcohol dehydrogenase: vitamin A alcohol and vitamin A aldehyde activities. Adv. Exp. Med. Biol. 328: 411–418.

    Article  PubMed  CAS  Google Scholar 

  • Posch, K.C., Boerman, M.H.E.M., Burns, R.D. and Napoli, J.L. (1991) Holocellular retinol binding protein as a substrate for microsomal retinal synthesis. Biochemistry 30: 6224–6230.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, A.B. and Sporn, M.B. (1984) Cellular biology and biochemistry of the retinoids. In: Sporn, M.B., Roberts, A.B. and Goodman, D.S. (eds.): The Retinoids Vol. 2, Academic, Orlando, pp. 209–286.

    Google Scholar 

  • Ruberte, E., Friederich, V., Chambon, P. and Morriss-Kay, G. (1993) Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development 118: 267–282.

    PubMed  CAS  Google Scholar 

  • Rugh, R. (1990) The Mouse: Its Reproduction and Development. Oxford Univ. Press, New York.

    Google Scholar 

  • Satre, M.A., Ugen, K.E. and Kochhar, D.M. (1992) Developmental changes in endogenous retinoids during pregnancy and embryogenesis in the mouse. Biol. Reprod. 46: 802–810.

    Article  PubMed  CAS  Google Scholar 

  • Shean, M.L. and Duester, G. (1992) The role of alcohol dehydrogenase in retinoic acid homeostasis and fetal alcohol syndrome. Alcohol and Alcoholism 28, Suppl. 2: 51–56.

    Google Scholar 

  • Smith, M., Hopkinson, D.A. and Harris, H. (1971) Developmental changes and polymorphism in human alcohol dehydrogenase. Ann. Hum. Genet. 34: 251–271.

    Article  PubMed  CAS  Google Scholar 

  • Van Ooij, C., Snyder, R.C., Paeper, B.W. and Duester, G. (1992) Temporal expression of the human alcohol dehydrogenase gene family during liver development correlates with differential promoter activation by HNF1, C/EBPa, LAP, and DBP. Mol. Cell. Biol. 12: 3023–3031.

    PubMed  Google Scholar 

  • Wagner, M., Thaller, C., Jessell, T. and Eichele, G. (1990) Polarizing activity and retinoid synthesis in the floor plate of the neural tube. Nature 345: 819–822.

    Article  PubMed  CAS  Google Scholar 

  • Wagner, M., Han, B. and Jessell, T.M. (1992) Regional differences in retinoid release from embryonic neural tissue detected by an in vitro reporter assay. Development 116: 55–66.

    PubMed  CAS  Google Scholar 

  • Yang, Z.N., Davis, G.J., Hurley, T.D., Stone, C.L., Li, T.-K. and Bosron, W.F. (1993) Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction. Alcohol. Clin. Exp. Res. 17: 496.

    Google Scholar 

  • Yasunami, M., Chen, C.-S. and Yoshida, A. (1991) A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme. Proc. Natl. Acad. Sci. USA 88: 7610–7614.

    Article  PubMed  CAS  Google Scholar 

  • Yost, R.W., Harrison, E.H. and Ross, A.C. (1988) Esterification by rat liver microsomes of retinol bound to cellular retinol-binding protein. J. Biol. Chem. 263: 18693–18701.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, California, 92037, USA

    Gregg Duester

Authors
  1. Gregg Duester
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Karolinska Institutet, Huddinge University Hospital, S-141 86, Huddinge, Sweden

    B. Jansson

  2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77, Stockholm, Sweden

    H. Jörnvall

  3. Department of Clinical Neuroscience, Karolinska Institutet, S-171 76, Stockholm, Sweden

    U. Rydberg  & L. Terenius  & 

  4. Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Avenue, 02115, Boston, MA, USA

    B. L. Vallee

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Duester, G. (1994). Retinoids and the alcohol dehydrogenase gene family. In: Jansson, B., Jörnvall, H., Rydberg, U., Terenius, L., Vallee, B.L. (eds) Toward a Molecular Basis of Alcohol Use and Abuse. Experientia, vol 71. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7330-7_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7330-7_28

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7332-1

  • Online ISBN: 978-3-0348-7330-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation