Aldose reductase (E.C. 18.104.22.168), an intracellular enzyme of polyol pathway, catalyzes NADPHdependent reduction of glucose to sorbitol. Under normoglycemia, most of the cellular glucose is phosphorylated into glucose-6-phosphate by hexokinase. A minor part of non-phosphorylated glucose enters the polyol pathway, the alternate route of glucose metabolism. However, under hyperglycemia, because of saturation of hexokinase with ambient glucose, aldose reductase is activated, leading to excessive production of sorbitol. Intracellular accumulation of sorbitol is thought to result in irreversible damage. In the diabetic eye, the increased sorbitol accumulation in retina has been implicated in the pathogenesis of retinopathy, characterized by pericyte loss, basal membrane thickening, the major ocular complications of diabetes. Nearly all diabetic subjects have the same degree of retinopathy after 20 years of diabetes. 50% of patients with insulin dependent diabetes mellitus have proliferative retinopathy after 15 years. In addition, macular edema frequently produces central vision loss and blindness most commonly in non-insulin dependent diabetes mellitus. Therefore, aldose reductase enzyme inhibition is becoming one of the therapeutic strategies that have been proposed to prevent or ameliorate long-term diabetic complications.
Pharmacology Department,Faculty of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451,Kingdom of Saudi Arabia.
Publication date: February 1, 2007
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Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.