Isolation and characterization of a new advanced glycation endproduct of dehydroascorbic acid and lysine.
Proteins are subject of posttranslational modification by sugars and their degradation products in vivo. The process is often referred as glycation. L-Dehydroascorbic acid (DHA), an oxidation product of L-ascorbic acid (vitamin C), is known as a potent glycation agent. A new product of modification of lysine epsilon -amino group by DHA was discovered as a result of the interaction between Boc-Lys and dehydroascorbic acid. The chromatographic and spectral analyses revealed that the structure of the product was 1-(5-ammonio-5-carboxypentyl)-3-oxido-4-(hydroxymethyl)pyridinium. The same compound was isolated from DHA modified calf lens protein after hydrolysis and chromatographic separation. The study confirmed that L-erythrulose is an important intermediate of modification of proteins by DHA. The structure of the reported product and in vitro experiments suggested that L-erythrulose could further transform to L-threose, L-erythrose and glycolaldehyde under conditions similar to physiological. The present study revealed that the modification of epsilon -amino groups of lysine residues by DHA is a complex process and could involve a number of reactive carbonyl species.
Argirov
Ognyan K
OK
Mason Eye Institute, University of Missouri-Columbia, 404 Portland Street, 65201, USA. argirovo@health.missouri.edu
Lin
Bin
B
Olesen
Paul
P
Ortwerth
Beryl J
BJ
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000737:chemistry*; D005136:Eye Proteins / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013780:Tetroses / Q000737:chemistry
D005136:Eye Proteins; D017127:Glycation End Products, Advanced; D013780:Tetroses; C040741:epsilon-tert-butyloxycarbonyl-lysine; C100073:erythrulose; D000079:Acetaldehyde; D008239:Lysine; C010972:glycolaldehyde; D003683:Dehydroascorbic Acid