Succination of proteins by fumarate - Mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes

被引：79

作者：

Biatnik, Matthew ^{[2
]}

Thorpe, Suzanne R. ^{[1
]}

Baynes, John W. ^{[1
,2
]}

机构：

[1] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA

[2] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA

来源：

MAILLARD REACTION: RECENT ADVANCES IN FOOD AND BIOMEDICAL SCIENCES | 2008年 / 1126卷

关键词：

protein; chemical modification; cysteine; diabetes; fumarate; glyceraldehyde-3-phosphate dehydrogenase; oxidative stress; mitochondrial stress; succination;

D O I：

10.1196/annals.1433.047

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein-a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.

引用

页码：272 / 275

页数：4

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