Metabolism and function of glutathione in the lens.
Metabolism and function of glutathione in the lens.
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DOI：
10.1002/9780470720875.ch5
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
V. Reddy;F. Giblin
中科院分区：
文献类型：
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作者：
V. Reddy;F. Giblin
哺乳动物晶状体含有异常高浓度的谷胱甘肽（GSH），在上皮中含量最高。谷胱甘肽主要以还原状态存在。正常晶状体中谷胱甘肽浓度较高，而大多数类型的白内障中谷胱甘肽浓度较低，这导致了许多关于谷胱甘肽在白内障形成中的作用的假设。这些假设是根据目前的证据来考虑的。谷胱甘肽在晶状体中合成和降解。这两个过程都需要ATP，而ATP主要来源于糖酵解。碳水化合物代谢也参与维持谷胱甘肽的还原状态。氧化谷胱甘肽（GSSG）的形成速率与通过生成NADPH刺激单磷酸己糖分流之间存在直接联系。GSH在晶状体中的一个可能功能是维持蛋白质的巯基（SH）基团处于还原状态，从而防止形成高分子量（HMW）蛋白质聚集体。x射线诱导的白内障中HMW蛋白通过二硫键形成以及从人白内障晶状体中分离的HMW蛋白中SH氧化的参与表明谷胱甘肽在保护SH蛋白群中的作用。晶状体中的谷胱甘肽也可能保护参与调节阳离子运输和通透性的关键谷胱甘肽群。对哺乳动物晶状体的研究表明，降低晶状体GSH浓度可导致对阳离子的渗透性增加和Na+，K+- atp酶的失活。离子分布变化的一个后果是抑制蛋白质合成，这可以解释白内障晶体停止生长的原因。谷胱甘肽还可以防止晶状体受到氧化损伤。谷胱甘肽代谢与H2O2解毒密切相关，通常存在于水体液中。分流活性受损或谷胱甘肽还原酶抑制的晶状体更容易受到过氧化物的氧化损伤。这可能有助于白内障的形成。
The mammalian lens contains an unusually high concentration of glutathione (GSH), the highest level being in the epithelium. GSH is present largely in the reduced state. The high concentration of GSH in a normal lens and the decreased concentration in most types of cataracts have led to many hypotheses on its role in cataract formation. These hypotheses are considered in the light of current evidence. GSH is synthesized and degraded in the lens. Both processes require ATP, derived largely from glycolysis. Carbohydrate metabolism is also involved in the maintenance of GSH in the reduced state. There is a direct link between the rate of formation of oxidized glutathione (GSSG) and the stimulation of the hexose monophosphate shunt through the generation of NADPH. One possible function of GSH in the lens is to maintain the thiol (SH) groups of proteins in the reduced state, thus preventing formation of high molecular weight (HMW) protein aggregates. The formation of HMW proteins in X-ray-induced cataracts through disulphide bond formation and the involvement of SH oxidation in HMW proteins isolated from human cataractous lenses suggest a role for GSH in protecting protein SH groups. GSH in the lens may also protect critical SH groups involved in regulating cation transport and permeability. Studies with mammalian lenses indicate that lowering the lens GSH concentration leads to increased permeability to cations and inactivation of Na+,K+-ATPase. A consequence of the changes in ion distribution is the inhibition of protein synthesis, which may explain the cessation of growth in cataractous lenses. GSH may also protect against oxidative damage to the lens. GSH metabolism is intimately involved in detoxification of H2O2, normally present in the aqueous humour. Lenses with impaired shunt activity or inhibited glutathione reductase are more susceptible to oxidative damage by peroxide. This may contribute to the formation of cataract.