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天冬氨酸转氨酶的糖化作用由甲基乙二醛引起,羟柠檬酸和尿酸的影响。

Glycation of aspartate aminotransferase by methylglyoxal, effect of hydroxycitric and uric acid.

机构信息

Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovského 1203, 50005, Hradec Kralove, Czech Republic.

出版信息

Mol Cell Biochem. 2009 Nov;331(1-2):215-23. doi: 10.1007/s11010-009-0161-y. Epub 2009 May 18.

Abstract

Glycation is a process closely related to the aging and pathogenesis of diabetic complications. Reactive alpha-dicarbonyl compounds (e.g., methylglyoxal) are formed during middle stage of glycation reaction. Compounds that would inhibit the glycation process have been seeked for years. The objective of this study was to investigate the inhibitory effect of hydroxycitric (0.25-2.5 mM) and uric acid (0.4-1.2 mM) on middle stage of protein glycation in vitro using the model containing aspartate aminotransferase (AST) and 0.5 mM methylglyoxal. Hydroxycitric acid, at all tested concentrations, reduced AST activity decrease and formation of fluorescent AGEs during incubation of the enzyme with methylglyoxal at 37 degrees C. This compound also prevented formation of high-molecular weight protein cross-links and changes in molecular charge of AST caused by glycation. Uric acid showed no positive anti-glycation activity. The results support the hypothesis that hydroxycitric acid has beneficial effects in controlling protein glycation.

摘要

糖基化是一个与糖尿病并发症的衰老和发病机制密切相关的过程。在糖基化反应的中期会形成活性α-二羰基化合物(例如甲基乙二醛)。多年来一直在寻找能够抑制糖基化过程的化合物。本研究的目的是使用包含天冬氨酸氨基转移酶(AST)和 0.5mM 甲基乙二醛的模型,研究羟基柠檬酸(0.25-2.5mM)和尿酸(0.4-1.2mM)对体外蛋白质糖基化中期的抑制作用。在 37°C 下,该酶与甲基乙二醛孵育时,羟基柠檬酸在所有测试浓度下均降低了 AST 活性下降和荧光 AGEs 的形成。该化合物还可防止糖化引起的高分子量蛋白质交联和 AST 分子电荷的变化。尿酸没有显示出积极的抗糖化活性。研究结果支持了羟基柠檬酸具有控制蛋白质糖基化的有益作用的假说。

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