Inhibition of glycosylation processes: the reaction between pyridoxamine and glucose.
Glycosylation of proteins by glucose produces toxic and immunogenic compounds called 'advanced glycosylation end products' (AGEs), which are the origin of pathological symptoms in various chronic diseases. In this work, a kinetic study of the reaction between glucose (2) and pyridoxamine (1)--a potent inhibitor of AGEs formation both in vivo and in vitro--was conducted. The NH2 group of pyridoxamine was found to react with the C=O group of glucose to form the Schiff base 9 (Scheme 2). Subsequently, the Schiff base gives rise to other products, including compound 3, pyridoxal, pyridoxine, and 4-pyridoxic acid. Compound 3 inhibits the Amadori rearrangement, and prevents the formation of other C=O groups capable of triggering glycosylation processes. Pyridoxal and pyridoxine can also inhibit protein glycosylation via other previously reported mechanisms.
Adrover
Miquel
M
Institut Universitari d'Investigació en Ciències de la Salut, Departament de Química, Universitat de les Illes Balears, E-07122 Palma de Mallorca.
Vilanova
Bartolomé
B
Muñoz
Francisco
F
Donoso
Josefa
J
D005947:Glucose / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000737:chemistry; D006031:Glycosylation; D007700:Kinetics; D015394:Molecular Structure; D011730:Pyridoxal / Q000737:chemistry; D011733:Pyridoxamine / Q000737:chemistry*; D011735:Pyridoxic Acid / Q000737:chemistry; D011736:Pyridoxine / Q000737:chemistry
D017127:Glycation End Products, Advanced; D011730:Pyridoxal; D011735:Pyridoxic Acid; D011733:Pyridoxamine; D005947:Glucose; D011736:Pyridoxine