Does sorbinil bind to the substrate binding site of aldose reductase?

Biochem Pharmacol. 1992 Dec 15;44(12):2427-9. doi: 10.1016/0006-2952(92)90693-d.

Abstract

With benzyl alcohol as the varied substrate, sorbinil was found to be a competitive inhibitor of aldose reductase, an enzyme implicated in the etiology of secondary diabetic complications. The K(is sorbinil) and the Vmax/Km (V/K) benzyl alcohol decreased at low pH with a pK of 7.5 and 7.7, respectively. These observations suggest that both sorbinil and benzyl alcohol bind to the same site on the enzyme. Active site inhibition by sorbinil is consistent with non-competitive inhibition patterns of sorbinil with nucleotide coenzyme or aldehyde as the varied substrate in the direction of aldehyde reduction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors
  • Aldehyde Reductase / metabolism*
  • Benzyl Alcohol
  • Benzyl Alcohols / metabolism
  • Binding Sites
  • Humans
  • Hydrogen-Ion Concentration
  • Imidazoles / metabolism*
  • Imidazolidines*
  • Kinetics
  • NADP / metabolism

Substances

  • Benzyl Alcohols
  • Imidazoles
  • Imidazolidines
  • NADP
  • Aldehyde Reductase
  • sorbinil
  • Benzyl Alcohol