Fernandes Aristi Potamitou, Holmgren Arne
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Antioxid Redox Signal. 2004 Feb;6(1):63-74. doi: 10.1089/152308604771978354.
Most cells contain high levels of glutathione and multiple glutaredoxins, which utilize the reducing power of glutathione to catalyze disulfide reductions in the presence of NADPH and glutathione reductase (the glutaredoxin system). Glutaredoxins, like thioredoxins, may operate as dithiol reductants and are involved as alternative pathways in cellular functions such as formation of deoxyribonucleotides for DNA synthesis (by reducing the essential enzyme ribonucleotide reductase), the generation of reduced sulfur (via 3'-phosphoadenylylsulfate reductase), signal transduction, and the defense against oxidative stress. The three dithiol glutaredoxins of E. coli with the active-site sequence CPYC and a glutathione binding site in a thioredoxin/glutaredoxin fold display surprisingly different properties. These include the inducible OxyR-regulated 10-kDa Grx1 or the highly abundant 24-kDa glutathione S-transferase-like Grx2 (with Grx3 it accounts for 1% of total protein). Glutaredoxins uniquely reduce mixed disulfides with glutathione via a monothiol mechanism where only an N-terminal low pKa Cys residue is required, by using their glutathione binding site. Glutaredoxins also catalyze formation of mixed disulfides (glutathionylation), which is an important redox regulatory mechanism, particularly in mammalian cells under oxidative stress conditions, to sense cellular redox potential.
大多数细胞含有高水平的谷胱甘肽和多种谷氧还蛋白，它们利用谷胱甘肽的还原能力，在烟酰胺腺嘌呤二核苷酸磷酸（NADPH）和谷胱甘肽还原酶存在的情况下催化二硫键还原（谷氧还蛋白系统）。谷氧还蛋白与硫氧还蛋白一样，可作为二硫醇还原剂发挥作用，并作为替代途径参与细胞功能，如DNA合成中脱氧核糖核苷酸的形成（通过还原关键酶核糖核苷酸还原酶）、还原态硫的生成（通过3'-磷酸腺苷-5'-磷酸硫酸还原酶）、信号转导以及抗氧化应激防御。大肠杆菌中具有活性位点序列CPYC且在硫氧还蛋白/谷氧还蛋白折叠中有谷胱甘肽结合位点的三种二硫醇谷氧还蛋白表现出惊人的不同特性。其中包括可诱导的、受OxyR调控的10 kDa谷氧还蛋白1（Grx1）或高度丰富的24 kDa谷胱甘肽S-转移酶样谷氧还蛋白2（Grx2，它与Grx3占总蛋白的1%）。谷氧还蛋白通过单硫醇机制独特地还原与谷胱甘肽形成的混合二硫键，该机制仅需要一个N端低pKa半胱氨酸残基，利用其谷胱甘肽结合位点。谷氧还蛋白还催化混合二硫键的形成（谷胱甘肽化），这是一种重要的氧化还原调节机制，特别是在氧化应激条件下的哺乳动物细胞中，用于感知细胞氧化还原电位。
