Stutchbury G M, Truscott R J
Australian Cataract Research Foundation, University of Wollongong, NSW.
Exp Eye Res. 1993 Aug;57(2):149-55. doi: 10.1006/exer.1993.1110.
The autoxidation and reactivity towards proteins of 3-hydroxykynurenine, a tryptophan metabolite found in the human lens, has been studied. At neutral pH, 3-hydroxykynurenine was readily oxidized using molecular oxygen with the formation of several coloured products. The autoxidation of both 3-hydroxykynurenine and the related aminophenol, 3-hydroxyanthranilic acid, was inhibited by the inclusion of sulphydryl compounds such as glutathione or cysteine. Covalent adducts involving the thiols were not observed with either aminophenol. 3-Hydroxykynurenine was found to react with proteins, including lens proteins, to produce brown-coloured polypeptides characterized by an indistinct long wavelength absorption. This protein tanning was inhibited by glutathione. Despite the presence of an amino group in the side chain of 3-hydroxykynurenine, this tanning of proteins was found to involve amino groups including those of lysine residues, as has been found for 3-hydroxyanthranilic acid. Although both aminophenols tanned polylysine, only 3-hydroxykynurenine induced precipitation of the polyamino acid. 3-Hydroxykynurenine tanned all of the purified crystallins but induced precipitation only in the case of alpha A-crystallin. The implications of these findings for senile cataract are discussed.
对人晶状体中发现的色氨酸代谢产物3-羟基犬尿氨酸的自氧化及其对蛋白质的反应性进行了研究。在中性pH值下，3-羟基犬尿氨酸很容易被分子氧氧化，生成几种有色产物。3-羟基犬尿氨酸和相关氨基酚3-羟基邻氨基苯甲酸的自氧化都受到巯基化合物如谷胱甘肽或半胱氨酸的抑制。两种氨基酚均未观察到与硫醇形成的共价加合物。发现3-羟基犬尿氨酸与包括晶状体蛋白在内的蛋白质发生反应，生成具有不明显长波长吸收特征的棕色多肽。这种蛋白质鞣制受到谷胱甘肽的抑制。尽管3-羟基犬尿氨酸侧链中存在氨基，但发现这种蛋白质鞣制涉及包括赖氨酸残基氨基在内的氨基，3-羟基邻氨基苯甲酸也是如此。虽然两种氨基酚都能使聚赖氨酸鞣制，但只有3-羟基犬尿氨酸能诱导聚氨基酸沉淀。3-羟基犬尿氨酸能使所有纯化的晶状体蛋白鞣制，但仅在αA-晶状体蛋白的情况下会诱导沉淀。讨论了这些发现对老年性白内障的意义。
