The Nature and Function of Aldehyde Reductases from Rat Brain

  • Anthony J. Turner
  • Susan R. Whittle

Abstract

Aldehyde reductases (EC 1.1.1.2) appear to play a number of distinct functions in cellular metabolism (Tipton et al., 1977). In neuronal tissue, they predominantly function in the reduction of aldehydes generated by oxidative deamination of monoamines or transamination of γ-aminobutyric acid (GABA). They may also play a role in the metabolism of aldoses and have been implicated in drug metabolism in liver (Turner and Hick, 1976; Bachur, 1976). In most tissues examined there exist several aldehyde reductases which may differ in subcellular location, inhibitor sensitivity and substrate specificity (Turner and Tipton, 1972a; Ris and von Wartburg, 1973; Anderson et al., 1976). The major reductase in all tissues (AR1 or “high-Km”) is characterized by a cytosolic location, a specific requirement for NADPH and a low specificity for aldehyde substrates. A feature of this enzyme is that it exhibits a substantial preference for 2-hydroxy aldehydes (Turner and Tipton, 1972b; Wermuth and Münch, 1979). Rat brain and other tissues contain at least one other aldehyde reductase (AR2 or “low-Km”) that is similar to or identical with aldose reductase (EC 1.1.1.21) (Turner and Tipton, 1972b). This latter enzyme has been implicated in some of the secondary effects of diabetes such as cataract formation (Gabbay and O’Sullivan, 1968). The relative contributions of these two reductases to the physiological metabolism of aldehydes is at present unclear. Some species may contain additional isoenzymes of aldehyde reductase (Ris and von Wartburg, 1973).

Keywords

Aldose Reductase Sodium Valproate Liver Cytosol 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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson, R. A., Meyerson, L. R.. and Tabakoff, B., 1976, Characteristics of enzymes forming 3-methoxy-4-hydroxyphenyl-ethylene glycol ( MOPEG) in brain, Neurochem. Res., 1: 525.Google Scholar
  2. Bachur, N. R., 1976, Cytoplasmic aldo-keto reductases: a class of drug metabolizing enzymes, Science, 193: 595.PubMedCrossRefGoogle Scholar
  3. Boghosian, R. A. and McGuinness, E. T., 1979, Affinity purification and properties of porcine brain aldose reductase, Biochim. Biophys. Acta., 567: 278.Google Scholar
  4. Erwin, V. G. and Dietrich, R. A., 1973, Inhibition of bovine brain aldehyde reductase by anti-convulsant compounds in vitro, Biochem. Pharmacol., 22: 2615.Google Scholar
  5. Gabbay, K. H. and O’Sullivan, J. B., 1968, The sorbitol pathway in diabetes and galactosemia, Diabetes, 17: 300.PubMedGoogle Scholar
  6. Meek, J. L. and Neff, N. H., 1972, Fluorimetric estimation of 4-hydroxy-4-methoxyphenylethylene glycol sulphate in brain, Brit. J. Pharmacol., 45: 435.Google Scholar
  7. Ris, M. M., Dietrich, R. A. and von Wartburg, J. P., 1975, Inhibition of aldehyde reductase isoenzymes in human and rat brain, Biochem. Pharmacol., 24: 1865.Google Scholar
  8. Ris, M. and von Wartburg, J. P., 1973, Heterogeneity of NADPH-dependent aldehyde reductase from human and rat brain, Eur. J. Biochem., 37: 69.Google Scholar
  9. Stockton, J., Pearson, A. G. M., West, L. J. and Turner, A. J., 1978, Purification of nucleotide-dependent enzymes by dye chromatography, Biochem. Soc. Trans., 6: 200.Google Scholar
  10. 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: 957.Google Scholar
  11. Thompson, S. T., Cass, K. H. and Stellwagen, E., 1975, Blue Dextran-Sepharose: an affinity column for the dinucleotide fold in proteins, Proc. Nat. Acad. Sci. U.S.A., 72: 669.Google Scholar
  12. Tipton, K. F., Houslay, M. D. and Turner, A. J., 1977, Metabolism of aldehydes in brain, Essays Neurochem. Neuropharmacol., 1: 103.Google Scholar
  13. Turner, A. J. and Hick, P. E., 1976, Metabolism of Daunorubicin by a barbiturate-sensitive aldehyde reductase from rat liver, Biochem. J., 159: 819.Google Scholar
  14. Turner, A. J., Illingworth, J. A. and Tipton, K. F., 1974, Simulation of biogenic amine metabolism in brain, Biochem. J., 144: 353.Google Scholar
  15. Turner, A. J. and Tipton, K. F., 1972a, The characterization of twoGoogle Scholar
  16. reduced nicotinamide-adenine dinucleotide phosphate-linked aldehyde reductases from pig brain, Biochem. J., 130: 765.Google Scholar
  17. Turner, A. J. and Tipton, K. F., 1972b, The purification and properties of an NADPH-linked aldehyde reductase from pig brain, Eur. J. Biochem., 30: 361.Google Scholar
  18. Watson, D. H., Harvey, J. M. and Dean, P. D. G., 1978, The selective retardation of NADP+-dependent dehydrogenases by immobilized Procion Red-HE3B, Biochem. J., 173: 591.Google Scholar
  19. Wermuth, B. and Minch, J. D. B., 1979, Reduction of biogenic alde-hydes by aldehyde reductase and alcohol dehydrogenase from human liver, Biochem. Pharmacol., 28: 1431.Google Scholar
  20. Whittle, S. R. and Turner, A. J., 1978, Effects of the anti-convulsant sodium valproate on y-aminobutyrate metabolism in ox brain, J. Neurochem., 31: 1453.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Anthony J. Turner
    • 1
  • Susan R. Whittle
    • 1
  1. 1.Department of BiochemistryUniversity of LeedsLeedsUK

Personalised recommendations