Naslov
Favored and disfavored pathways of protein crosslinking by glucose: glucose lysine dimer (GLUCOLD) and crossline versus glucosepane

Autori
Nemet, Ina ; Strauch, Christopher M. ; Monnier, Vincent M.

Izvornik
Amino Acids (0939-4451) 40 (2011), 1; 167-181

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
advanced glycation end-product; Maillard reaction; glycation; crosslink; diabetes

Sažetak
We describe the isolation and molecular characterization of a novel glucose-lysine dimer crosslink 1, 3-bis-(5-amino-5-carboxypentyl)-4-(1ˈ, 2ˈ, 3ˈ, 4ˈ-tetrahydroxybutyl)-3H-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 N6-1, 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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA