Abstract
Evidence is presented for two new forms of mouse liver and kidney aldehyde reductase activity (designated AHR-3 and AHR-4) resolved using cellulose acetate electrophoresis zymogram techniques and stained by glyceraldehyde and NADPH as substrate and coenzyme, respectively. Activity variants were observed for those isozymes among inbred strains of mice and used in a genetic analyses to support a proposal for two new genetic loci (Ahr-3 and Ah-4) which control the activity phenotype for these isozymes. Segregation analysis indicated that these loci are separately localized on the mouse genome, with Ahr-3 positioned on the distal end of chromosome 7. Liver AHR-2 (or hexonate dehydrogenase) exhibited no detectable phenotypic variation among the 44 inbred strains of mice examined. The AHR-3 and AHR-4 isozymes were readily distinguished from AHR-1 [or aldehyde reductase A2, described previously by Duley and Holmes (Biochem. Genet. 20:1067, 1982)], hexonate dehydrogenase (AHR-2), and alcohol dehydrogenase A2 in terms of their differential substrate, coenzyme, and inhibitor specificities.
Similar content being viewed by others
References
Algar, E. M., Seeley, T.- L., and Holmes, R. S. (1983). Purification and molecular properties of mouse alcohol dehydrogenase isozymes. Eur. J. Biochem. 137139.
Bachur, N. R. (1976). Cytoplasmic aldo-keto reductases: A class of drug metabolizing enzymes. Science 193595.
Branlant, G. (1982). Properties of an aldose reductase from pig lens. Eur. J. Biochem. 12999.
Cash, C. D., Maitre, M., and Mandel, P. (1979). Purification from human brain and some properties of two NADPH-linked aldehyde reductases which reduce succinic semialdehyde to 4-hydroxybutyrate. J. Neurochem. 331169.
Cromlish, J. A., and Flynn, T. G. (1983a). Pig muscle aldehyde reductase. Identity of pig muscle aldehyde reductase with pig lens aldose reductase and with the low Km aldehyde reductase of pig brain and pig kidney. J. Biol. Chem. 2583583.
Cromlish, J. A., and Flynn, T. G. (1983b). Purification and characterization of two aldose reductase isoenzymes from rabbit muscle. J. Biol. Chem. 2583416.
Daly, A. K., and Mantle, T. J. (1982). Purification and characterization of the multiple forms of aldehyde reductase in ox kidney. Biochem. J. 205373.
De Lorenzo, R. J., and Ruddle, F. H. (1969). Genetic control of two electrophoretic variants of glucose phosphate isomerase in the mouse (Mus musculus). Biochem. Genet. 3151.
Duley, J. A., and Holmes, R. S. (1982). Biochemical genetics of aldehyde reductase in the mouse: Ahr-1—a new locus linked to the alcohol dehydrogenase gene complex on chromosome 3. Biochem. Genet. 201067.
Erwin, V. G., and Deitrich, R. A. (1972). Heterogeneity of alcohol-dehydrogenase enzymes in various tissues. Biochem. Pharmacol. 212915.
Flynn, T. G. (1982). Aldehyde reductases: Monomeric NADPH-dependent oxidoreductases with multifunctional potential. Biochem. Pharmacol. 312705.
Flynn, T. G., Shires, J., and Walton, D. (1975). Properties of the nicotinamide adenine dinucleotide phosphate-dependent aldehyde reductase from pig kidney. J. Biol. Chem. 2502933.
Henderson, N. S. (1965). Isozymes of isocitrate dehydrogenase: Subunit structure and intracellular location. J. Exp. Zool. 158263.
Hers, H. G. (1960). L'aldose reductase. Biochim. Biophys. Acta 37120.
Holmes, R. S. (1978). Genetics and ontogeny of aldehyde dehydrogenase isozymes in the mouse: Localization of Ahd-1 encoding the mitochondrial isozyme on chromosome 4. Biochem. Genet. 161207.
Holmes, R. S. (1979). Genetics and ontogeny of alcohol dehydrogenase isozymes in the mouse: Evidence for cis-acting regulator gene (Adt-1) controlling C2 isozyme expression in reproductive tissues and close linkage of Adh-3 and Adt-1 on chromosome 3. Biochem. Genet. 17461.
Holmes, R. S., and Masters, C. J. (1967). The developmental multiplicity and isoenzyme status of cavian esterases. Biochim. Biophys. Acta 132379.
Holmes, R. S., Duley, J. A., and Burnell, J. N. (1983). The alcohol dehydrogenase gene complex on chromosome 3 of the mouse. In Rattazzi, M. C., Scandalios, J. G., and Whitt, G. S. (eds.), Isozymes: Current Topics in Biological and Medical Research Alan R. Liss, New York, Vol. 8, p. 155.
Kaufman, E. E., Nelson, T., Goochee, C., and Sokoloff, L. (1979). Purification and characterization of an NADP-linked alcohol oxidoreductase which catalyses the interconversion of hydroxybutyrate and succinic semialdehyde. J. Neurochem. 32699.
Moonsammy, G. I., and Stewart, M. A. (1967). Purification and properties of brain aldose reductase and L-hexonate dehydrogenase. J. Neurochem. 141187.
O'Brien, M. M., and Schofield, P. J. (1980). Polyol pathway enzymes of human brain. Partial purification and properties of aldose reductase and hexonate dehydrogenase. Biochem. J. 18721.
O'Brien, M. M., Schofield, P. J., and Edwards, M. R. (1982). Inhibition of human brain aldose reductase and hexonate dehydrogenase by alrestatin and sorbinil. J. Neurochem. 39810.
Peters, J., and Nash, H. R. (1977). Polymorphism of esterase II in Mus musculus, a further esterase locus on chromosome 8. Biochem. Genet. 15217.
Rivett, A. J., Smith, I. L., and Tipton, K. F. (1981). Purification of the high-Km aldehyde reductase from rat brain and liver and ox brain. Biochem. J. 197473.
Sawada, H., and Hara, A. (1979). The presence of two NADPH-linked aromatic aldehydeketone reductases different from aldehyde reductase in rabbit liver. Biochem. Pharmacol. 281089.
Seeley, T.- L., Mather, P. B., and Holmes, R. S. (1984). Electrophoretic analyses of alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde reductase, aldehyde oxidase and xanthine oxidase from horse tissues. Comp. Biochem. Physiol. 78B131.
Sheaff, C. M., and Doughty, C. C. (1976). Physical and kinetic properties of homogeneous bovine lens aldose reductase. J. Biol. Chem. 2512696.
Shows, T. B., Ruddle, F. H., and Roderick, E. H. (1969). Phosphoglucomutase electrophoretic variants in the mouse. Biochem. Genet. 325.
Shows, T. B., Chapman, V. M., and Ruddle, F. H. (1970). Mitochondrial malate dehydrogenase and malic enzyme: Mendelian inherited electrophoretic variants in the mouse. Biochem. Genet. 4707.
Tipton, K. F., Houslay, M. D., and Turner, A. J. (1977). Metabolism of aldehydes in brain. Essays Neurochem. Neuropharmacol. 1103.
Tulsiani, D. R. P., and Touster, O. (1977). Resolution and partial characterization of two aldehyde reductases of mammalian liver. J. Biol. Chem. 2522545.
Turner, A. J., and Hryszko, J. (1980). Isolation and characterization of rat liver aldehyde reductase. Biochim. Biophys. Acta 613256.
Turner, A. J., and Tipton, K. F. (1972). The characterization of two reduced nicotinamide-adenine dinucleotide phosphate-linked aldehyde reductases from pig brain. Biochem. J. 130765.
Turner, A. J., and Whittle, S. R. (1981). Functions of aldehyde reductases. Biochem. Soc. Trans. 9279.
van Heyningen, R. (1959). Metabolism of xylose by the lens. 2. Rat lens in vivo and in vitro. Biochem. J. 73193.
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. 2523821.
Wermuth, B., Burgisser, H., Bohren, K., and von Wartburg, J. P. (1982). Purification and characterization of human brain aldose reductase. Eur. J. Biochem. 127279.
Whittle, S. R., and Turner, A. J. (1981). Differential sensitivity of aldehyde reductase isozymes to sodium valproate. Biochim. Biophys. Acta 65794.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mather, P.B., Holmes, R.S. Aldehyde reductase isozymes in the mouse: Evidence for two new loci and localization of Ahr-3 on chromosome 7. Biochem Genet 23, 483–496 (1985). https://doi.org/10.1007/BF00499088
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00499088