Formation pathways for lysine-arginine cross-links derived from hexoses and pentoses by Maillard processes: unraveling the structure of a pentosidine precursor.
Covalently cross-linked proteins are among the major modifications caused by the advanced Maillard reaction. So far, the chemical nature of these aggregates and their formation pathways are largely unknown. Synthesis and unequivocal structural characterization are reported for the lysine-arginine cross-links N(6)-(2-([(4S)-4-ammonio-5-oxido-5-oxopentyl]amino)-5-[(2S,3R)-2,3,4- trihydroxybutyl]-3,5-dihydro-4H-imidazol-4-ylidene)-l-lysinate (DOGDIC 12), N(6)-(2-([(4S)-4-ammonio-5-oxido-5-oxopentyl]amino)-5-[(2S)-2,3-dihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene)-l-lysinate (DOPDIC 13), and 6-((6S)-2-([(4S)-4-ammonio-5-oxido-5-oxopentyl] amino)-6-hydroxy-5,6,7,7a-tetrahydro-4H-imidazo[4,5-b] pyridin-4-yl)-l-norleucinate (pentosinane 10). For these compounds, as well as for glucosepane 9 and pentosidine 11, the formation pathways could be established by starting from native carbohydrates, Amadori products, and 3-deoxyosones, respectively. Pentosinane 10 was unequivocally proven to be an important precursor of pentosidine 11, which is a well established fluorescent indicator for advanced glycation processes in vivo. The Amadori products are shown to be the pivots in the formation of the various cross-links 9-13. The bicyclic structures 9-11 are directly derived from aminoketoses, whereas 12 and 13 stem from reaction with the 3-deoxyosones. All products 9-13 were identified and quantified from incubations of bovine serum albumin with the respective 3-deoxyosone or carbohydrate. From these results it seems fully justified to expect both glucosepane 9 and DOGDIC 12 to constitute important in vivo cross-links.
Biemel
K M
KM
Institut für Lebensmittelchemie (170), Universität Hohenheim, Garbenstrasse 28, D-70593 Stuttgart, Germany.
Reihl
O
O
Conrad
J
J
Lederer
M O
MO
D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D001381:Azepines / Q000138:chemical synthesis*; D006601:Hexoses / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis*; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D015416:Maillard Reaction; D008956:Models, Chemical; D009952:Ornithine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D010429:Pentoses / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism
D001381:Azepines; D006601:Hexoses; D007093:Imidazoles; C432395:N(5)-(4-(5-amino-5-carboxypentyl)azepino(2,3-d)-5,6,7,8,8a-pentahydro-6,7-dihydroxyimidazol-2-yl)ornithinate; C432396:N(5)-(4-(5-amino-5-carboxypentyl)pyridino(2,3-d)imidazol-2-yl)ornithinate; C432393:N(6)-(2-((4-ammonio-5-oxido--5-oxopentyl)amino)-5-(2,3-dihydroxypropyl)-3,5-dihydro-4H-imidazol-4-ylidene)lysinate; C432392:N(6)-(2-((4-ammonio-5-oxido-5-oxopentyl)amino)-5-(2,3,4-trihydroxybutyl)3,5-dihydro-4H-imidazol-4-ylidene)lysinate; D010429:Pentoses; D012710:Serum Albumin, Bovine; D001120:Arginine; C062187:pentosidine; D009952:Ornithine; D008239:Lysine