NEW METABOLITES AND PATHWAYS IN THE MAMMALIAN LENS

山梨醇-3-磷酸（S3 P）和果糖-3-磷酸的鉴别 (F3P)在哺乳动物透镜中， 在这个组织中进行新陈代谢。 这条通路似乎与 醛糖还原酶途径，因为S3 P浓度升高 (and糖尿病透镜中的F3 P）在较小程度上受到 醛糖还原酶抑制剂sorbinil。 本提案的目的是确定相关化合物是否 与新的途径参与细胞病变观察糖尿病 透镜。 其中一种新发现的化合物果糖-3-磷酸是一种 一种磷酸单酯，包括甘油醛 磷酸盐、磷酸二羟基丙酮和葡萄糖-3-磷酸。 化合物 这种类型的蛋白质相对不稳定， 已知有效无机磷酸盐和α-二羰基化合物 交联剂 我们认为一些加速的细胞损伤 糖尿病透镜中的果糖浓度增加可能导致 3-磷酸盐及其分解产物3-脱氧葡萄糖酮， 晶状体蛋白的交联增加。 在这项研究中，我们打算测试这一假设，并确定和 表征新的代谢物，反应和酶参与 通路

Identification of sorbitol-3-phosphate (S3P) and fructose-3-phosphate (F3P) in the mammalian lens suggests a possible new pathway for glucose metabolism in this tissue. This pathway appears to be connected with the aldose reductase pathway since the elevation in the concentration of S3P (and to a lesser extent F3P) in the diabetic lens is inhibited by the aldose reductase inhibitor sorbinil. The purpose of this proposal is to determine if the compounds associated with the new pathway are involved in the cytopathy observed the diabetic lens. One of the newly identified compounds, fructose-3-phosphate, is a member of a class of phosphate monoesters which include glyceraldehyde phosphate, dihhydroxyacetone phosphate and glucose-3-phosphate. Compounds of this type are relatively labile and dephosphorylate easily forming inorganic phosphate and alpha dicarbonyl compounds known to be potent crosslinking agents. We propose that some of the accelerated cell damage in the diabetic lens may result from increased concentrations of fructose- 3-phosphate and its breakdown product 3-deoxy-glucosone, which cause increased crosslinking of lenticular proteins. In this study we intend to test this hypothesis and to identify and characterize the metabolites, reactions and enzymes involved in the new pathway.