title: Theoretical studies on models of lysine-arginine cross-links derived from α-oxoaldehydes: a new mechanism for glucosepane formation.
abstract: Availability and high reactivity of α-oxoaldehydes have been approved by experimental techniques not only in vivo systems but also in foodstuffs. In this article we re-examine the mechanism of glucosepane formation by using computational model chemistry. Density functional theory has been applied to propose a new mechanism for glucosepane formation through reaction of α-oxoaldehydes with methyl amine (MA) and methyl guanidine (MGU) models of lysine and arginine residues respectively. This non enzymatic process can be described in three main steps: (1) Schiff base formation from methyl amine, methyl glyoxal (MGO) (2) addition of methyl guanidine and (3) addition of glyceraldehyde. We show that this process is thermodynamically possible and presents a rate-determining step with a reasonable free energy barrier equal to 37.8 kcal mol(-1) in water solvent. Comparisons were done with the mechanism formation of GODIC (glyoxal-derived imidazolium cross-link) and MODIC (methyl glyoxal-derived imidazolium cross-link), two other important cross-links in vivo.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Iran.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Nasiri
authors.forename: Mansour
authors.initials: M
authors.lastname: Zahedi
authors.forename: Hélène
authors.initials: H
authors.lastname: Jamet
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D007661:Ketoses / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D015416:Maillard Reaction; D008744:Methylamines / Q000737:chemistry; D008760:Methylguanidine / Q000737:chemistry; D008958:Models, Molecular; D008962:Models, Theoretical; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000447:Aldehydes; D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D007661:Ketoses; D008744:Methylamines; D011506:Proteins; D008760:Methylguanidine; C543060:glucosepane; D001120:Arginine; D008239:Lysine