Lloyd A J, Gray R G, Green A
Department of Clinical Chemistry, Children's Hospital, Birmingham, UK.
J Inherit Metab Dis. 1995;18(1):48-55. doi: 10.1007/BF00711372.
Thiol groups are important components of proteins and their oxidation can lead to a substantial loss of protein function. Patients with two apparently unrelated inborn errors of metabolism, tyrosinaemia type 1 and glutathione synthetase deficiency, have been reported to show reduced cell glutathione concentrations. We have found that not only glutathione but also protein thiol concentrations are reduced in the liver in tyrosinaemia type 1 patients. We also report a case of glutathione synthetase deficiency with a substantial deficiency of liver 4-fumarylacetoacetate hydrolase and provide evidence that glutathione, or some small-molecular-weight thiol, is essential for maintaining stability of this enzyme in vitro. Our results suggest that the availability of thiol groups may modify the phenotype of tyrosinaemia type 1 and that liver 4-fumarylacetoacetate hydrolase deficiency may be a secondary complicating factor in some forms of glutathione synthetase deficiency.
硫醇基团是蛋白质的重要组成部分，其氧化会导致蛋白质功能大幅丧失。据报道，患有两种明显不相关的先天性代谢缺陷病——1型酪氨酸血症和谷胱甘肽合成酶缺乏症的患者，细胞内谷胱甘肽浓度降低。我们发现，1型酪氨酸血症患者的肝脏中不仅谷胱甘肽浓度降低，蛋白质硫醇浓度也降低。我们还报告了一例谷胱甘肽合成酶缺乏症患者，其肝脏中4-富马酰乙酰乙酸水解酶严重缺乏，并提供证据表明谷胱甘肽或某些小分子量硫醇在体外对维持该酶的稳定性至关重要。我们的结果表明，硫醇基团的可用性可能会改变1型酪氨酸血症的表型，并且肝脏4-富马酰乙酰乙酸水解酶缺乏可能是某些形式的谷胱甘肽合成酶缺乏症的继发性并发症因素。
