Theoretical studies on models of lysine-arginine cross-linksderived from α-oxoaldehydes: a new mechanismfor glucosepane formation

Availability and high reactivity of α-oxoaldehydeshave been approved by experimental techniques not only invivo systems but also in foodstuffs. In this article we reexaminethe mechanism of glucosepane formation by usingcomputational model chemistry. Density functional theory hasbeen applied to propose a new mechanism for glucosepaneformation through reaction of α-oxoaldehydes with methylamine (MA) and methyl guanidine (MGU) models of lysineand arginine residues respectively. This non enzymatic processcan be described in three main steps: (1) Schiff base formationfrom methyl amine, methyl glyoxal (MGO) (2) addition ofmethyl guanidine and (3) addition of glyceraldehyde. Weshow that this process is thermodynamically possible andpresents a rate-determining step with a reasonable free energybarrier equal to 37.8 kcal mol-1 in water solvent. Comparisonswere done with the mechanism formation of GODIC(glyoxal-derived imidazolium cross-link) and MODIC(methyl glyoxal-derived imidazolium cross-link), two otherimportant cross-links in vivo.