The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect.
Amadori compounds act as precursors in the formation of advanced glycation end products (AGEs) by non-enzymatic protein glycation, which are involved in ensuing protein damage. Pyridoxamine is a potent drug against protein glycation, and can act on several pathways in the glycation process. Nevertheless, the pyridoxamine inhibition action on Amadori compounds oxidation is still unclear. In this work, we have studied the Schiff base formation between pyridoxamine and various Amadori models at pH 7.4 at 37 degrees C in the presence of NaCNBH(3). We detected an adduct formation, which suggests that pyridoxamine reacts with the carbonyl group in Amadori compounds. The significance of this mechanism is tested by comparison of the obtained kinetics rate constants with that obtained for 4-(aminomethyl)-pyridine, a structural analogue of pyridoxamine without post-Amadori action. We also study the chelating effect of pyridoxamine on metal ions. We have determined the complexation equilibrium constants between pyridoxamine, N-(1-deoxy-d-fructos-1-yl)-l-tryptophan, aminoguanidine, and ascorbic acid in the presence of Zn(2+). The results show that the strong stability of pyridoxamine complexes is the key in its post-Amadori inhibition action. On the other hand results explain the lack of inhibition of aminoguanidine (a glycation inhibitor) in the post-Amadori reactions.
Adrover
Miquel
M
Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, Cra. Valldemossa km 7.5, Edifici Mateu Orfila i Rotger, E-07122 Palma de Mallorca, Spain.
Vilanova
Bartolomé
B
Frau
Juan
J
Muñoz
Francisco
F
Donoso
Josefa
J
D000596:Amino Acids / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005632:Fructose / Q000031:analogs & derivatives / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011733:Pyridoxamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012545:Schiff Bases / Q000737:chemistry; D013237:Stereoisomerism; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D000596:Amino Acids; D002614:Chelating Agents; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D006146:Guanidines; D008024:Ligands; D009942:Organometallic Compounds; D012545:Schiff Bases; C040009:1-(N-tryptophan)-1-deoxyfructose; D005632:Fructose; D011733:Pyridoxamine; D014364:Tryptophan; D005947:Glucose; D015032:Zinc; D001205:Ascorbic Acid; C004479:pimagedine