S-(2-Succinyl)cysteine

A novel chemical modification of tissue proteins by a Krebs cycle intermediate

Nathan L. Alderson, Yuping Wang, Matthew Blatnik, Norma Frizzell, Michael D. Walla, Timothy J. Lyons, Nadja Alt, James Carson, Ryoji Nagai, Suzanne R. Thorpe, John W. Baynes

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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), Nε-(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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume450
Issue number1
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Citric Acid Cycle
Chemical modification
Fumarates
Tissue
Muscle Proteins
Skin
Proteins
Collagen
Rat control
Addition reactions
Advanced Glycosylation End Products
Glyceraldehyde-3-Phosphate Dehydrogenases
Succinic Acid
Metabolism
Serum Albumin
Cysteine
S-(2-succinyl)cysteine
Rats
Blood Proteins
Skeletal Muscle

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Alderson, N. L., Wang, Y., Blatnik, M., Frizzell, N., Walla, M. D., Lyons, T. J., ... Baynes, J. W. (2006). S-(2-Succinyl)cysteine: A novel chemical modification of tissue proteins by a Krebs cycle intermediate. Archives of Biochemistry and Biophysics, 450(1), 1-8. https://doi.org/10.1016/j.abb.2006.03.005

S-(2-Succinyl)cysteine : A novel chemical modification of tissue proteins by a Krebs cycle intermediate. / Alderson, Nathan L.; Wang, Yuping; Blatnik, Matthew; Frizzell, Norma; Walla, Michael D.; Lyons, Timothy J.; Alt, Nadja; Carson, James; Nagai, Ryoji; Thorpe, Suzanne R.; Baynes, John W.

In: Archives of Biochemistry and Biophysics, Vol. 450, No. 1, 01.06.2006, p. 1-8.

Research output: Contribution to journalArticle

Alderson, NL, Wang, Y, Blatnik, M, Frizzell, N, Walla, MD, Lyons, TJ, Alt, N, Carson, J, Nagai, R, Thorpe, SR & Baynes, JW 2006, 'S-(2-Succinyl)cysteine: A novel chemical modification of tissue proteins by a Krebs cycle intermediate', Archives of Biochemistry and Biophysics, vol. 450, no. 1, pp. 1-8. https://doi.org/10.1016/j.abb.2006.03.005
Alderson, Nathan L. ; Wang, Yuping ; Blatnik, Matthew ; Frizzell, Norma ; Walla, Michael D. ; Lyons, Timothy J. ; Alt, Nadja ; Carson, James ; Nagai, Ryoji ; Thorpe, Suzanne R. ; Baynes, John W. / S-(2-Succinyl)cysteine : A novel chemical modification of tissue proteins by a Krebs cycle intermediate. In: Archives of Biochemistry and Biophysics. 2006 ; Vol. 450, No. 1. pp. 1-8.
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