Acetaldehyde Hydrate and Carbonic Anhydrase: Possible Roles in the Inhibition of Brain Aldehyde Dehydrogenase

  • R. P. Sheridan
  • C. A. Deakyne
  • L. C. Allen


One biochemical explanation for the chronic and addictive effects of ethanol involves a relationship between biogenic aldehydes, brain aldehyde dehydrogenase and acetaldehyde, the principal metabolic product of ethanol. We suggest here the possibility that acetaldehyde hydrate may act as an especially strong inhibitor of aldehyde dehydro-genase. Aldehyde hydrates are known to strongly inhibit aldehyde dehydrogenase as well as a number of other aldehyde oxidizing enzymes and it may be that acetaldehyde hydrate acts as a transition state or activated intermediate inhibitor. It is also suggested that carbonic anhydraae, which catalyzes the very rapid equilibrium between acetaldehyde and its hydrate, may play a role in this process.


Carbonic Anhydrase Biogenic Amine Aldehyde Dehydrogenase Triose Phosphate Isomerase Free Aldehyde 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bodley, F. H. and Blair, A. H., 1971, Substrate characteristics of human alcohol dehydrogenase, Can. J. Biochem., 49: 1.PubMedGoogle Scholar
  2. Cohen, G., 1976, Alkaloid products in the metabolism of alcohol and biogenic amines, Biochem. Pharm., 25: 1123.PubMedCrossRefGoogle Scholar
  3. Collins, A. C., Cashow, J. L. and Davis, V. E., 1973, Alteration of norepinephrine metabolism by barbiturates, Biochem. Pharm., 23: 1877.Google Scholar
  4. Collins, M. A. and Bigdeli, M. G., 1975, Biosynthesis of tetrahydro-isoquinoline alkaloids in brain and other tissues of ethanol intoxicated rats, Adv. Exp. Med. Biol., 59: 79.PubMedGoogle Scholar
  5. Davis, V. E. and Walsh, M. J., 1970, Alcohol, amines and alkaloids: a possible biochemical basis for alcohol addiction, Science, 167: 1005.PubMedCrossRefGoogle Scholar
  6. Davis, V. W., 1971, Alcohol and aberrant metabolism of biogenic amines, in: Biological Aspects of Alcohol, M. K. Roach, Austin.Google Scholar
  7. Davis, V. E., Cushaw, J. L. and McMurty, K. K., 1975, Disposition of catecholamine-derived alkaloids in mammalian systems, Adv. Exp. Med. Biol., 59: 65.PubMedGoogle Scholar
  8. Deitrich, R. A. and Erwin, V. G., 1971, Mechanism of inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate, Molec. Pharm., 7: 301.PubMedGoogle Scholar
  9. Deitrich, R. A. and Erwin, V. G., 1975, Involvement of biogenic amine metabolism in ethanol addiction, Fed. Proc., 34: 1962.PubMedGoogle Scholar
  10. Duncan, R. J. S., 1973, Inhibition of alcohol and aldehyde dehydro-genase by propanolol, Molec. Pharm., 9: 191.PubMedGoogle Scholar
  11. Eckfeldt, J., Mope, L., Takio, K., and Yonetani, T., 1976, Horse liver aldehyde dehydrogenase-purification and characterization of the two isoenzymes, J. Biol. Chem., 251: 236.Google Scholar
  12. Erwin, V. G. and Deitrich, R. A., 1966, Brain aldehyde dehydrogenase: localization, purification, and properties, J. Biol. Chem:, 241: 3533.PubMedGoogle Scholar
  13. a)Feldman, R. I. and Weiner, H., 1971, Horse liver aldehyde dehydrogenase. 1. purification and characterization, J. Biol. Chem., 247: 260.Google Scholar
  14. b)Feldman, R. I. and Weiner, H., 1971, Horse liver aldehyde dehydrogenase. 2. kinetics and mechanistic implications of dehydrogenase and esterase activity, J. Biol. Chem., 247: 267.Google Scholar
  15. Gregory, D., Goodman, P. A., and Meany, J. E., 1972, Xanthine oxidasecatalyzed oxidation of aldehydes: oxidation of aliphatic aldehydes and 2-pyridine carboxaldehyde and 4-pyridinecarboxaldehyde, Biochemistry, 11: 4472.PubMedCrossRefGoogle Scholar
  16. Goodman, P. A. and Meany, J. E., 1974, Substrate and product inhibition in xanthine oxidase-catalyzed oxidation of acetaldehyde, Biochemistry, 13: 3254.PubMedCrossRefGoogle Scholar
  17. Lieber, C. S., Hasumura, Y., and De Carli, L. M., 1974, Interaction of ethanol with liver microsomes, in: Alcohol and Aldehyde Metabolizing Systems R. G. Thurman, J. R. Williamson, T. Yonetani, and B. Chase, eds., Academic Press, New York.Google Scholar
  18. Maren, T. H., 1967, Carbonic anhydrase: chemistry, physiology, and inhibition, Physiol. Rev., 47: 595.PubMedGoogle Scholar
  19. Mikeska, J. A. and Klemm, W. R., 1970, Evidence against a role of acetaldehyde in electroencephalographic signs of ethanol-induced intoxication, Science, 203: 276.CrossRefGoogle Scholar
  20. Myers, R. D. and Melchoir, C. L., 1977, Alcohol drinking: abnormal intake caused by tetrahydropapaverolin in brain, Science, 196: 554.PubMedCrossRefGoogle Scholar
  21. Pocker, Y. and Meany, J. E., 1965, The catalytic versatility of erythrocyte carbonic anhydrase, I. kinetic studies of the enzyme catalyzed hydration of acetaldehyde, Biochemistry, 4: 2535.CrossRefGoogle Scholar
  22. Pocker, Y. and Dickerson, D. C., 1968, The catalytic versatility of erthrocyte carbonic anhydrase. U. kinetic studies of the enzyme catalyzed hydration of pyridine aldehydes, Biochemistry, 6: 239.Google Scholar
  23. Pocker, Y. and Meany, J. E., 1967, The catalytic versatility of carbonic anhydrase from erythrocytes. The enzyme catalyzed hydration of acetaldehyde, J. Amer. Chem. Soc., 87: 1809.CrossRefGoogle Scholar
  24. Pocker, Y. and Dickerson, D. C., 1968, The catalytic versatility of erythrocyte carbonic anhydrase. V. kinetic studies of the enzyme catalyzed hydration of aliphatic aldehydes, Biochemistry, 7: 1995.PubMedCrossRefGoogle Scholar
  25. Pocker, Y., Meany, J. E. and Davis, B. C., 1974, Alpha-keto esters as substrates of erythrocyte carbonic anhydrase. kinetic study of enzyme-catalyzed hydration and methyl and ethyl prynvate, Biochemistry, 13: 1411.PubMedCrossRefGoogle Scholar
  26. Schnuckit, M. A. and Rayses, V., 1979, Ethanol ingestion: differences in blood acetaldehyde concentrations in relatives of alcoholics and controls, Science, 203: 54.CrossRefGoogle Scholar
  27. (a).
    Sidhu, R. S. and Blair, A. H., 1975, Human liver aldehyde dehydrogenase-esterhase activity, J. Biol. Chem., 250: 7894.PubMedGoogle Scholar
  28. (b).
    Sidhu, R. S. and Blair, A. H., 1975, Human liver aldehyde dehydro-genase-kinetics of aldehyde oxidation, J. Biol. Chem., 250: 7899.PubMedGoogle Scholar
  29. Tabakoff, B. and Gelpke, C. G., 1975, Alcohol and aldehyde metabolism in brain, Adv. Exp. Med. Biol., 56: 141.PubMedCrossRefGoogle Scholar
  30. Tabakoff, B. Anderson, R. A., and Ritzmann, R. F., 1976, Brain acetaldehyde after ethanol administration, Biochem. Pharm., 25:1305.PubMedCrossRefGoogle Scholar
  31. Tienhaara, R. and Meany, J. E., 1973, Lactate dehydrogenase-catalyzed reduction of pyruvate-active substrate and substrate inhibition, Biochemistry, 12: 2067.PubMedCrossRefGoogle Scholar
  32. Trentham, D. R., McMurray, C. H. and Pogson, C. I., 1972, The active chemical state of d-gylceraldehyde-3-phosphate in its reactions with d-gyleraldehyde-3-phosphate dehydrogenase, aldolase and triose phosphate isomerase, Biochem. J., 114: 19.Google Scholar
  33. Ungar, F., Tabakoff, B., and Alivisatos, S. G. A., 1973, Inhibition of bindings of aldehydes of biogenic amines in tissues, Biochem. Pharm., 22: 1905.PubMedCrossRefGoogle Scholar
  34. Wartburg, J. P., Berger, D., Ris, M. M., and Tabakoff, B., 1975, Enzymes of biogenic aldehyde metabolism, Adv. Exp. Med. Biol., 59: 119.Google Scholar
  35. Weiner, H., Hu, J. H. H. and Sanny, C. G., 1976, Rate-limiting steps for the esterase and dehydrogenase reaction catalyzed by horse liver aldehyde dehydrogenase, J. Biol. Chem., 251: 3853.PubMedGoogle Scholar
  36. Weiner, J., in press, Aldehyde dehydrogenase: mechanisms of action and possible physiological roles, Adv. Exp. Med. Biol.Google Scholar
  37. Wiseman, J. S. and Abeles, R. H., 1979, Mechanisms of inhibition of aldehyde dehydrogenase by cyclopropanone hydrate and the mushroom toxic coprene, Biochemistry, 18: 427.PubMedCrossRefGoogle Scholar
  38. Wolfenden, R., 1976, Transition state analogue inhibitors and enzyme catalysis, Ann. Rev. Biophys. Bioeng., 5: 271.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • R. P. Sheridan
    • 1
    • 3
  • C. A. Deakyne
    • 2
    • 3
  • L. C. Allen
    • 3
  1. 1.The Institute for Cancer ResearchFoxchase, PhiladelphiaUSA
  2. 2.Dept. of ChemistryCollege of the Holy CrossWorcesterUSA
  3. 3.Department of ChemistryPrincton UniversityPrinctonUSA

Personalised recommendations