Alderson Nathan L, Wang Yuping, Blatnik Matthew, Frizzell Norma, Walla Michael D, Lyons Timothy J, Alt Nadja, Carson James A, Nagai Ryoji, Thorpe Suzanne R, Baynes John W
Department of Chemistry and Biochemistry, University of South Carolina, USA.
Arch Biochem Biophys. 2006 Jun 1;450(1):1-8. doi: 10.1016/j.abb.2006.03.005. Epub 2006 Mar 22.
S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.
S-(2-琥珀酰基)半胱氨酸（2SC）已被确定为血浆蛋白、人血浆白蛋白的非巯基白蛋白部分、人皮肤胶原蛋白以及大鼠骨骼肌蛋白和尿液中的一种化学修饰。随着年龄增长，人皮肤胶原蛋白中的2SC会增加，并且与对照大鼠相比，糖尿病大鼠肌肉蛋白中的2SC也会增加。皮肤胶原蛋白和肌肉蛋白中2SC的浓度与晚期糖基化/脂氧化终产物（AGE/ALE）N(ε)-(羧甲基)赖氨酸（CML）的浓度密切相关。在生理pH值下，2SC是由半胱氨酸巯基与富马酸发生迈克尔加成反应形成的。富马酸而非琥珀酸在体外会使巯基酶甘油醛-3-磷酸脱氢酶失活，同时形成2SC。2SC是三羧酸循环中的代谢中间体对蛋白质进行自发化学修饰的首个实例。这些观察结果确定富马酸为内源性亲电试剂，并提示富马酸在代谢调节中发挥作用。
