Open AccessInhibition and activation studies on sheep liver sorbitol dehydrogenase
Author(s) -
LINDSTAD Rune I.,
HERMANSEN Leonila F.,
McKINLEYMcKEE John S.
Publication year - 1994
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1994.tb18799.x
Subject(s) - sorbitol dehydrogenase , alcohol dehydrogenase , sorbitol , chemistry , enzyme , dehydrogenase , ternary complex , biochemistry , non competitive inhibition , dissociation constant , aldehyde reductase , alcohol oxidoreductase , stereochemistry , nad+ kinase , aldose reductase , receptor
Reversible inhibition and activation, as well as protection against affinity labelling with dl ‐2‐bromo‐3‐(5‐imidazolyl)propionic acid, of sheep liver sorbitol dehydrogenase have been studied. The results presented are discussed in terms of enzyme active‐site properties and may have potential applications for drug design. Kinetics with mainly sorbitol competitive inhibitors reveals that aliphatic thiols are generally the most potent inhibitors of enzyme activity. Inhibition and inactivation by heterocyclics parallel that seen previously with sorbitol dehydrogenase from other sources as well as with alcohol dehydrogenase from yeast. However, there are significant differences in relation to the structurally similar horse liver alcohol dehydrogenase, as the catalytic zinc of sorbitol dehydrogenase is more easily removed by chelating molecules. Several aldose reductase inhibitors are shown to also inhibit sorbitol dehydrogenase, but at concentrations unlikely to be reached clinically. Enzyme activation has been observed with various compounds, in particular halo‐alcohols and detergents. Several inhibitors provide competitive protection against enzyme inactivation by dl ‐2‐bromo‐3‐(5‐imidazolyl)propionic acid. This enables the dissociation constants for binary enzyme‐inhibitor complexes to be determined. NADH protects noncompetitively against inactivation. The presence of some binary and ternary enzyme‐NADH complexes is indicated from fluorescence emission spectra, as a shift in the fluorescence maximum and intensity is observed due to their formation.