Does sorbinil bind to the substrate binding site of aldose reductase?
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.
Liu
S Q
SQ
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555.
Bhatnagar
A
A
Srivastava
S K
SK
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000378:metabolism*; D048289:Imidazolidines; D007700:Kinetics; D009249:NADP / Q000378:metabolism
D001592:Benzyl Alcohols; D007093:Imidazoles; D048289:Imidazolidines; D009249:NADP; D000449:Aldehyde Reductase; C026411:sorbinil; D019905:Benzyl Alcohol