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- Title
Favored and disfavored pathways of protein crosslinking by glucose: glucose lysine dimer (GLUCOLD) and crossline versus glucosepane.
- Authors
Nemet, Ina; Strauch, Christopher; Monnier, Vincent
- Abstract
We describe the isolation and molecular characterization of a novel glucose-lysine dimer crosslink 1,3-bis-(5-amino-5-carboxypentyl)-4-(1′,2′,3′,4′-tetrahydroxybutyl)-3 H-imidazolium salt, named GLUCOLD. GLUCOLD was easily formed from the Amadori product (fructose-lysine). However, when BSA was incubated with 100 mM glucose for 25 days, the levels of the lysine-lysine glucose crosslinks GLUCOLD and CROSSLINE were only 21 and <1 pmol/mg, respectively, compared to 611 pmol/mg protein for the lysine-arginine GLUCOSEPANE crosslink, in spite of more than 20 potential lysine-lysine crosslinking sites in the protein. Mechanistic investigation revealed that metal-free phosphate ions catalyzed formation of fructose-lysine and all three crosslinks from amino acids, while cationic MOPS buffer had an opposite effect. This together with the rapid formation of N-1,4-dideoxy-5,6-dioxoglucosone derivatives by dicarbonyl trapping agents, such as 1,2-diaminobenzene or γ-guanidinobutyric acid, strongly suggests that enolization of the Amadori product and trapping of the 5,6-dioxo derivative by arginine residues constitutes the major pathway for glucose-mediated crosslinking in proteins.
- Subjects
PROTEIN crosslinking; GLUCOSE; DIMERS; IONS; FRUCTOSE; LYSINE; GLYCOSYLATION; ARGININE; DIABETES; MAILLARD reaction
- Publication
Amino Acids, 2011, Vol 40, Issue 1, p167
- ISSN
0939-4451
- Publication type
Article
- DOI
10.1007/s00726-010-0631-2