Journal
MAILLARD REACTION: RECENT ADVANCES IN FOOD AND BIOMEDICAL SCIENCES
Volume 1126, Issue -, Pages 272-275Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1433.047
Keywords
protein; chemical modification; cysteine; diabetes; fumarate; glyceraldehyde-3-phosphate dehydrogenase; oxidative stress; mitochondrial stress; succination
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Funding
- NIDDK NIH HHS [DK-19971, R37 DK019971, R37 DK019971-31] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK019971, R01DK019971] Funding Source: NIH RePORTER
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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.
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