Comparison of aldose reductase inhibitors in vitro. Effects of enzyme purification and substrate type.
Aldose reductase (EC 1.1.1.21) was purified approximately 5000-fold from bovine lens by ammonium sulphate fractionation and chromatography on DEAE-Sephacel and Matrex OA. Inhibition of this enzyme was found to depend upon the assay substrate. Tested against the purest form of enzyme, the inhibitor Sorbinil gave IC50 values of approximately 100 microM with the model substrate 4-nitrobenzaldehyde (4NB) and 0.4-1.4 microM with the physiological substrate glucose. A similar effect of substrate was found for the inhibitor Statil (IC50 450-750 nM with 4NB, 26-71 nM with glucose substrate). The implications of these results towards the assessment of aldose reductase inhibitors in vitro are discussed.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D001547:Benzaldehydes / Q000378:metabolism; D002417:Cattle; D005947:Glucose / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000201:enzymology; D010793:Phthalazines / Q000494:pharmacology; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001547:Benzaldehydes; D007093:Imidazoles; D048289:Imidazolidines; D010793:Phthalazines; C042829:ponalrestat; C029915:4-nitrobenzaldehyde; C037070:M 79175; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose