NEW METABOLITES AND PATHWAYS IN THE MAMMALIAN LENS

山梨醇-3-磷酸(S3P)和果糖-3-磷酸的鉴定 哺乳动物晶状体中的(F3P)提示了一种可能的葡萄糖新途径 这种组织中的新陈代谢。这条通路似乎与 S3P浓度升高后的醛糖还原酶途径 糖尿病晶状体中的F3P(在较小程度上)被抑制 醛糖还原酶抑制剂索比尼。 这项建议的目的是确定化合物是否与 与新途径有关的糖尿病细胞病变的观察 镜头。其中一种新鉴定的化合物，3-磷酸果糖，是一种 一类含甘油醛的磷酸单酯的成员 磷酸、二羟丙酮磷酸和葡萄糖-3-磷酸。化合物 这类物质相对不稳定，容易脱磷形成 已知有效的无机磷酸盐和α-二酮类化合物 交联剂。我们认为一些加速的细胞损伤 可能是由于果糖浓度增加所致- 3-磷酸及其分解产物3-脱氧葡萄糖苷，引起 豆状蛋白的交联度增加。 在这项研究中，我们打算检验这一假设，并确定和 描述新的代谢产物、反应和酶的特征 路径。

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.