Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase inhibitors.
Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several test systems. These RLAR inhibitors were found not to produce significant inhibition of genetically-linked reductases (aldehyde reductase, ALR), catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR), functionally distinct oxidoreductases (glutathione reductase, GR, lactate dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase (TS). These data suggest that aldose reductase differs significantly from other oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose reductase selectivity demonstrated by the arylsulfonylamino acids suggests that these compounds may not inhibit other key metabolic transformations in various cell types and that they may function as selective probes for studies of the relationship between aldose reductase mediated biochemical changes and the pathologies of chronic diabetes.
Davis
R A
RA
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, AL 36849.
Mayfield
C A
CA
Aull
J L
JL
DeRuiter
J
J
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001190:Arylsulfonates / Q000378:metabolism; D005260:Female; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D000596:Amino Acids; D001190:Arylsulfonates; D010088:Oxidoreductases; D000449:Aldehyde Reductase; D013940:Thymidylate Synthase