Multiple Aldehyde Reductases of Human Brain

  • Paula L. Hoffman
  • Bendicht Wermuth
  • Jean-Pierre von Wartburg


Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme (“SSA reductase”) differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of γ-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles.


Human Brain Biogenic Amine Aldose Reductase Succinic Semialdehyde Aldehyde Reductase 
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. Ahmed, N. K., Felsted, R. L. and Bachur, N. R., 1978, Heterogeneity of anthracycline antibiotic carbonyl reductases in mammalian levels, Biochem. Pharmacol., 27: 2713–2719.Google Scholar
  2. Anderson, R. A., Meyerson, L. R. and Tabakoff, B., 1974, Characteristics of enzymes forming 3-methoxy-4-hydroxyphenylethyleneglycol ( MOPEG) in brain, Neurochem. Res., 1: 525–540.Google Scholar
  3. Anderson, R. A., Ritzmann, R. F. and Tabakoff, B., 1977, Formation of gamma hydroxybutyrate in brain, J. Neurochem., 28: 633–639.PubMedCrossRefGoogle Scholar
  4. Ando, N., Gold, B. I., Bird, E. D. and Roth, R. H., 1979, Regional brain levels of y-hydroxybutyrate in Huntington’s disease, J. Neurochem, 32: 617–622.PubMedCrossRefGoogle Scholar
  5. Cash, C., Maitre, M. and Mandel, P., 1978, Purification de deux semi-aldehydes succinique réductases de cerveau humain, C. R. Acad. Sci. Paris, Ser. D., 286: 1829–1832.Google Scholar
  6. Clements, R. S., Jr., Weaver, J. P. and Winegrad, A. I., 1969, The distribution of polyol: NADP oxidoreductase in mammalian tissues, Biochem. Biophys. Res. Commun., 37: 347–353.Google Scholar
  7. Davidson, W. S., Walton, D. J. and Flynn, T. G., 1979, A comparative study of the tissue and species distribution of NADPH-dependent aldehyde reductase, Comp. Biochem. Physiol., 60B: 309–315.Google Scholar
  8. Doherty, J. D., Hattox, S. E., Snead, O. C. and Roth, R. H., 1978, Identification of endogenous y-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain, J. Pharmacol. Exptl. Ther., 207: 130–139.Google Scholar
  9. Dons, R. F. and Doughty, C. C., 1976, Isolation and characterization of aldose reductase from calf brain, Biochim. Biophys. Acta., 452: 1–12.Google Scholar
  10. Felsted, R. L., Richter, D. R. and Bachur, N. R., 1977, Rat liver aldehyde reductase, Biochem. Pharmacol., 26: 1117–1124.Google Scholar
  11. Gabbay, K. H. and Cathcart, E., 1974, Purification and immunologic identification of aldose reductases, Diabetes, 23: 460–468.PubMedGoogle Scholar
  12. Hoffman, P. L., Wermuth, B. and von Wartburg, J.P., in press, Human brain aldehyde reductases: relationship to SSA reductase and aldose reductase, J. Neurochem.Google Scholar
  13. Jedziniak, J. A. and Kinoshita, J. H., 1971, Activators and inhibitors of lens aldose reductase, Invest. Ophthalmol., 10: 357–366.Google Scholar
  14. Kaufman, E. E., Nelson, T., Goochee, C. and Sokoloff, L., 1979, Purification and characterization of NADP+-linked alcohol oxidoreductase which catalyzes the interconversion of y-hydroxybutyrate and succinic semialdehyde, J. Neurochem., 32: 699–712.PubMedCrossRefGoogle Scholar
  15. Lee, C-Y., Lappi, D. A., Wermuth, B., Everse, J. and Kaplan, N. 0., 1974, 8-(6-aminohexyl)-amino-adenine nucleotide derivatives for affinity chromatography, Arch. Biochem. Biophys., 163: 561–569.Google Scholar
  16. Levine, W., Giuditta, A., England, S. and Shecker, H. J., 1960, Brain diaphorases, J. Neurochem., 6: 28–36.CrossRefGoogle Scholar
  17. Ris, M. M. and von Wartburg, J-P., 1973, Heterogeneity of NADPH-dependent aldehyde reductase from human and rat brain, Eur. J. Biochem., 36: 69–77.Google Scholar
  18. Schaeff, C. M. and Doughty, C. C., 1976, Physical and kinetic properties of homogeneous bovine lens aldose reductase, J. Biol. Chem., 251: 2696–2702.Google Scholar
  19. Snead, 0. C. III, 1978, Gamma-hydroxybutyrate in the monkey. I. electroencephalographic, behavioral and pharmacokinetic studies, Neurology, 28: 636–648.Google Scholar
  20. Stenflo, J., 1978, Vitamin K, prothrombin and a-carboxyglutamic acid, Adv. Enzymol., 46: 1–31.Google Scholar
  21. Tabakoff, B., Anderson, R. A. and Alivisatos, S. G. A., 1973, Enzymatic reduction of “biogenic” aldehydes in brain, Mol. Pharmacol., 9: 428–437, 1973.Google Scholar
  22. Tabakoff, B. and von Wartburg, J-P., 1975, Separation of aldehyde reductases and alcohol dehydrogenase from brain by affinity chromatography: metabolism of succinic semialdehyde and ethanol, Biochem. Biophys. Res. Commun., 63: 959–966.Google Scholar
  23. Tabakoff, B., 1977, Brain aldehyde dehydrogenases and reductases, in: “Structure and Function of Monoamine Enzymes,” E. Usdin, N. Weaver and M.B. H. Youdim, ed., Marcell Dekker, New York.Google Scholar
  24. Varma, S. D., Mikuni, I. and Kinoshita, J. H., 1975, Flavonoids as inhibitors of lens aldose reductases, Science, 188: 1215–1216.PubMedCrossRefGoogle Scholar
  25. Walton, D. J., 1973, Stereochemistry of reduction of D-glyceraldehyde catalyzed by a NADP-dependent dehydrogenase from skeletal muscle, Biochem., 12: 3472–3478.CrossRefGoogle Scholar
  26. Wermuth, B., Munch, J. D. B. and von Wartburg, J-P., 1977, Purification and properties of NADPH-dependent aldehyde reductase from human liver, J. Biol. Chem., 252: 3821–2828.PubMedGoogle Scholar
  27. Whittle, S. R. and Turner, A. J., 1978, Effects of the anticonvulsant sodium valproate on y-aminobutyrate and aldehyde metabolism in ox brain, J. Neurochem., 31: 1453–1459.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Paula L. Hoffman
    • 1
    • 2
  • Bendicht Wermuth
    • 2
  • Jean-Pierre von Wartburg
    • 2
  1. 1.Department of Physiology and BiophysicsIllinois Medical CenterChicagoUSA
  2. 2.Medizinisch-Chemisches InstitätUniversitat BernBernSwitzerland

Personalised recommendations