Department of Exercise Science, School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
Free Radic Res. 2011 Jan;45(1):101-9. doi: 10.3109/10715762.2010.524643. Epub 2010 Oct 22.
Cysteine is arguably the most reactive amino acid in protein. A wide range of cysteine derivatives is formed in vivo, resulting from oxidation, nitrosation, alkylation and acylation reactions. This review describes succination of proteins, an irreversible chemical modification of cysteine by the Krebs cycle intermediate, fumarate, yielding S-(2-succinyl)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane and develop in concert with mitochondrial and oxidative stress in diabetes. Increased succination of glyceraldehyde-3-phosphate dehydrogenase explains the loss in specific activity of this enzyme in muscle of streptozotocin-diabetic rats and increased succination of adiponectin may explain the decreased secretion of adiponectin from adipose tissue in type 2 diabetes. In addition to GAPDH and adiponectin, other succinated proteins identified in adipocytes include cytoskeletal proteins (tubulin, actin) and chaperone proteins in the endoplasmic reticulum. Succination of adipocyte protein in vitro is inhibited by uncouplers of oxidative phosphorylation and by inhibitors of ER stress. 2SC serves as a biomarker of mitochondrial stress and recent studies suggest that succination is the mechanistic link between mitochondrial and ER stress in diabetes.
半胱氨酸可以说是蛋白质中最具反应性的氨基酸。体内形成了广泛的半胱氨酸衍生物，这些衍生物来自氧化、亚硝化、烷基化和酰化反应。这篇综述描述了蛋白质的琥珀酰化，这是一种由克雷布斯循环中间产物富马酸盐引起的半胱氨酸的不可逆化学修饰，生成 S-(2-琥珀酰)半胱氨酸（2SC）。细胞内富马酸盐浓度和蛋白质的琥珀酰化随着线粒体内膜的超极化而增加，并与糖尿病中的线粒体和氧化应激协同发展。3-磷酸甘油醛脱氢酶的琥珀酰化增加解释了链脲佐菌素糖尿病大鼠肌肉中该酶比活性的丧失，而脂联素的琥珀酰化增加可能解释了 2 型糖尿病中脂肪组织中脂联素分泌减少的原因。除了 GAPDH 和脂联素，在脂肪细胞中鉴定的其他琥珀酰化蛋白质还包括细胞骨架蛋白（微管蛋白、肌动蛋白）和内质网中的伴侣蛋白。氧化磷酸化解偶联剂和内质网应激抑制剂抑制体外脂肪细胞蛋白的琥珀酰化。2SC 是线粒体应激的生物标志物，最近的研究表明，琥珀酰化是糖尿病中线粒体和内质网应激之间的机制联系。
