Fructose induced deactivation of glucose-6-phosphate dehydrogenase activity and its prevention by pyruvate: Implications in cataract prevention
Fructose induced deactivation of glucose-6-phosphate dehydrogenase activity and its prevention by pyruvate: Implications in cataract prevention
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DOI：
10.1080/10715769800300351
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发表时间：
1998-01-01
影响因子：
3.3
通讯作者：
Varma, SD
中科院分区：
文献类型：
--
作者：
Zhao, W;Devamanoharan, PS;Varma, SD
葡萄糖-6-磷酸脱氢酶（glucose-6-phosphate dehydrogenase，G6 PDH）是一种重要的透镜酶，可将约14%的组织葡萄糖转移到磷酸己糖旁路。酶的这种显著活性的主要功能是支持还原性生物合成，以及维持组织中的还原环境，以防止氧自由基诱导的损伤和随后的白内障形成。糖是众所周知的白内障发生剂之一。一些报告表明，糖在糖尿病和正常衰老中的白内障发生作用是由蛋白质（包括酶）的糖化以及随后形成更复杂和生物学上无活性或有害的结构引发的。在糖尿病透镜中，果糖的浓度显著超过葡萄糖的浓度，表明果糖基化的贡献可能大于葡萄糖基化的贡献。进行这些研究是为了进一步检查除了糖化之外，果糖产生氧自由基和随后某些酶的氧化修饰可能是白内障发生过程的重要参与者的可能性。这一假设通过使用G6 PDH进行了检验。将酶与各种水平的果糖（0-20 mM）孵育，并将其活性测定为时间的函数。这导致其活性的显著损失，这被超氧化物歧化酶、过氧化氢酶、甘露醇和肌醇阻止。最有趣的是，丙酮酸在0.2和1.0 mM之间的水平也提供了实质性的保护。因此，这些结果在进一步阐明糖如果糖使酶失活的机制的同时，也证明了在糖尿病和其他在发病过程中涉及氧自由基的残疾中，丙酮酸和其他此类酮酸治疗性预防白内障的可能性。
Glucose-6-phosphate dehydrogenase (G6PDH) is an important lens enzyme diverting about 14% of the tissue glucose to the hexose monophosphate shunt pathway. The main function of such a pronounced activity of the enzyme is to support reductive biosyntheses, as well as to maintain a reducing environment in the tissue so as to prevent oxy-radical induced damage and consequent cataract formation. Sugars are one of the well-known cataractogenic agents. Several reports suggest that the cataractogenic effect of the sugars in diabetes as well as in normal aging is initiated by the glycation of the proteins including the enzymes and subsequent formation of more complex and biologically inactive or harmful structures. In a diabetic lens the concentration of fructose exceeds significantly the concentration of glucose, suggesting that the contribution of fructosylation may be greater than that of glucosylation. These studies were undertaken to examine further the possibility that in addition to glycation, generation of oxygen free radicals by fructose and consequent oxidative modifications in certain enzymes may be an important participant in the cataractogenic process. This hypothesis was tested by using G6PDH. The enzyme was incubated with various levels of fructose (0-20 mM) and its activity determined as a function of time. This led to a significant loss of its activity, which was prevented by superoxide dismutase, catalase, mannitol and myoinositol. Most interestingly, pyruvate at levels between 0.2 and 1.0 mM also offered substantial protection. Hence, the results, while elucidating further the mechanism of enzyme deactivation by sugars such as fructose, also demonstrate the possibility of therapeutic prevention of cataracts by pyruvate and other such keto acids, in diabetes and other disabilities involving oxygen free radicals in the pathogenetic process.