Since its discovery in 1958 in the lens of cows, ophthalmic acid (OPH) has stood in the shadow of its anti-oxidant analog: glutathione (GSH). Lacking the thiol group that gives GSH many of its important properties, ophthalmic acid's function has remained elusive, and it has been widely presumed to be an accidental product of the same enzymes. In this review, we compile evidence demonstrating that OPH is a ubiquitous metabolite found in bacteria, plants, fungi, and animals, produced through several layers of metabolic regulation. We discuss the limitations of the oft-repeated suggestions that aberrations in OPH levels should solely indicate GSH deficiency or oxidative stress. Finally, we discuss the available literature and suggest OPH's role in metabolism as a GSH-regulating tripeptide; controlling both cellular and organelle influx and efflux of GSH, as well as modulating GSH-dependent reactions and signaling. Ultimately, we hope that this review reinvigorates and directs more research into this versatile metabolite.

中文翻译：

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眼酸是一种谷胱甘肽调节三肽

自从 1958 年在牛的晶状体中发现以来，眼酸 (OPH) 一直处于其抗氧化剂类似物谷胱甘肽 (GSH) 的阴影之下。由于缺乏赋予谷胱甘肽许多重要特性的硫醇基团，邻苯二甲酸的功能仍然难以捉摸，人们普遍认为它是相同酶的偶然产物。在这篇综述中，我们收集了证据，证明 OPH 是细菌、植物、真菌和动物中普遍存在的代谢物，通过多层代谢调节产生。我们讨论了经常重复的建议的局限性，即 OPH 水平的异常应该仅表明 GSH 缺乏或氧化应激。最后，我们讨论了现有文献并提出了 OPH 作为 GSH 调节三肽在代谢中的作用；控制细胞和细胞器的 GSH 流入和流出，以及调节 GSH 依赖性反应和信号传导。最终，我们希望这篇综述能够重振并指导更多对这种多功能代谢物的研究。