ALDOSE REDUCTASE CATALYSIS AND CRYSTALLOGRAPHY - INSIGHTS FROM RECENTADVANCES IN ENZYME STRUCTURE AND FUNCTION

Enhanced metabolism of glucose via the polyol pathway may play an impo rtant role in the pathogenesis of diabetic retinopathy, neuropathy, an d nephropathy. Aldose reductase catalyzes the NADPH-dependent conversi on of glucose to sorbitol, the first step in the polyol pathway. Inter ruption of the polyol pathway by inhibition of aldose reductase holds considerable promise as a therapeutic measure to prevent or delay the onset and severity of these late complications of diabetes. Dramatic a dvances in our understanding of the molecular biology, enzymology, and three-dimensional structure of aldose reductase have occurred in rece nt years, providing new and challenging insights into the enzyme's cat alytic mechanism. Recent developments in structure determination of al dose reductase and the implications for evaluation and development of aldose reductase inhibitors are summarized.