Inhibition of Aldehyde Reductase by Carboxylic Acids
Aldehyde reductase (EC 22.214.171.124) and aldose reductase (EC 126.96.36.199) are structurally related, monomeric oxidoreductases that catalyze the NADPH-dependent reduction of a variety of aliphatic, aromatic and sugar aldehydes. For most substrates Km values of aldose reductase are one to two orders of magnitude lower than those of aldehyde reductase. Exceptions are anionic aldehydes, e.g. succinic semialdehyde, 4-carboxybenzaldehyde and glucuronate, which are metabolized much more efficiently by aldehyde than aldose reductase. The partiality of aldehyde reductase for negatively charged substrates has been attributed to the presence of an anion binding site, most probably an arginine residue, in the substrate binding domain of the active site (Davidson and Flynn, 1979; Branlant et al., 1981; Bohren et al., 1987).
KeywordsValproic Acid Aldose Reductase Arginine Residue Aldose Reductase Inhibitor Succinic Semialdehyde
Unable to display preview. Download preview PDF.
- Bohren, K.M., von Wartburg, J-P., and Wermuth, B., 1981, Inactivation of carbonyl reductase from human brain by phenylglyoxal and 2,3-butane -dione: a comparison with aldehyde reductase and aldose reductase, Biochim. Biophys. Acta ,916:185.Google Scholar
- Cleland, W.W., 1963, The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II, Inhibition: Nomenclature and theory, Biochim. Biophys. Acta ,284:427.Google Scholar
- Schofield, P.J., de Jongh, K.S., Smith, M.M., and Edwards, M.R., 1987 Inhibition of aldehyde reductase, Progr. Clin. Biol. Res. ,232:287Google Scholar
- Wermuth, B., 1987, Inhibition of aldehyde reductase: Structure-function relationships, International Workshop on Aldose Reductase Inhibitors, Honolulu, Dec. 1–10 ,Abstract C4.3.Google Scholar