Petrash J M, Tarle I, Wilson D K, Quiocho F A
Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri.
Diabetes. 1994 Aug;43(8):955-9. doi: 10.2337/diab.43.8.955.
Enhanced metabolism of glucose via the polyol pathway may play an important role in the pathogenesis of diabetic retinopathy, neuropathy, and nephropathy. Aldose reductase catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step in the polyol pathway. Interruption 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 advances in our understanding of the molecular biology, enzymology, and three-dimensional structure of aldose reductase have occurred in recent years, providing new and challenging insights into the enzyme's catalytic mechanism. Recent developments in structure determination of aldose reductase and the implications for evaluation and development of aldose reductase inhibitors are summarized.
通过多元醇途径增强葡萄糖代谢可能在糖尿病视网膜病变、神经病变和肾病的发病机制中起重要作用。醛糖还原酶催化NADPH依赖的葡萄糖向山梨醇的转化，这是多元醇途径的第一步。通过抑制醛糖还原酶来阻断多元醇途径，作为预防或延缓糖尿病这些晚期并发症的发生和严重程度的治疗措施，具有很大的前景。近年来，我们对醛糖还原酶的分子生物学、酶学和三维结构的理解有了显著进展，为该酶的催化机制提供了新的、具有挑战性的见解。本文总结了醛糖还原酶结构测定的最新进展及其对醛糖还原酶抑制剂评估和开发的意义。
