2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine) is a newly identified advanced glycation end product in cataractous and aged human lenses.
Post-translational modifications of proteins take place during the aging of human lens. The present study describes a newly isolated glycation product of lysine, which was found in the human lens. Cataractous and aged human lenses were hydrolyzed and fractionated using reverse-phase and ion-exchange high performance liquid chromatography (HPLC). One of the nonproteinogenic amino acid components of the hydrolysates was identified as a 3-hydroxypyridinium derivative of lysine, 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine). The compound was synthesized independently from 3-hydroxypyridine and methyl 2-[(tert-butoxycarbonyl)amino]-6-iodohexanoate. The spectral and chromatographic properties of the synthetic OP-lysine and the substance isolated from hydrolyzed lenses were identical. HPLC analysis showed that the amounts of OP-lysine were higher in water-insoluble compared with water-soluble proteins and was higher in a pool of cataractous lenses compared with normal aged lenses, reaching 500 pmol/mg protein. The model incubations showed that an anaerobic reaction mixture of Nalpha-tert-butoxycarbonyllysine, glycolaldehyde, and glyceraldehyde could produce the Nalpha-t-butoxycarbonyl derivative of OP-lysine. The irradiation of OP-lysine with UVA under anaerobic conditions in the presence of ascorbate led to a photochemical bleaching of this compound. Our results argue that OP-lysine is a newly identified glycation product of lysine in the lens. It is a marker of aging and pathology of the lens, and its formation could be considered as a potential cataract risk-factor based on its concentration and its photochemical properties.
Argirov
Ognyan K
OK
Mason Eye Institute, University of Missouri, Columbia, Missouri 65201, USA. argirovo@health.missouri.edu
Lin
Bin
B
Ortwerth
Beryl J
BJ
D000368:Aged; D000375:Aging; D001205:Ascorbic Acid / Q000737:chemistry; D002208:Caproates / Q000737:chemistry* / Q000378:metabolism; D002386:Cataract / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D007908:Lens, Crystalline / Q000378:metabolism*; D008027:Light; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D008956:Models, Chemical; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
C484321:2-amino-6-(3-oxidopyridinium-1-yl)hexanoic acid; D002208:Caproates; D017127:Glycation End Products, Advanced; D011726:Pyridinium Compounds; D014867:Water; C037652:hexanoic acid; D008239:Lysine; D001205:Ascorbic Acid