Nε-(1-Carboxymethyl)-L-lysine-d3 (CML-d3) is intended for use as an internal standard for the quantification of CML by GC- or LC-MS. CML is an advanced glycation end product (AGE), produced by the oxidative modification of glycated proteins during oxidative stress.1,2,3 Levels of CML increase with aging and during diabetes, cancer, vascular disease, and other pathologies marked by oxidative stress.1,4,5 CML activates the membrane-bound receptor for AGEs (RAGE), triggering signaling through MAPKs and NF-κB, whereas truncation of RAGE produces a soluble protein that binds CML and reduces signaling.6,7
1.Requena, J.R., Ahemd, M.U., Fountain, C.W., et al.Carboxymethylethanolamine, a biomarker of phospholipid modification during the maillard reaction in vivoThe Journal of Biological Chemisty272(28)17473-17479(1997) 2.Ahmed, M.U., Brinkmann, F.E., Degenhardt, T.P., et al.Nε-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteinsBiochem. J.324(Pt 2)565-570(1997) 3.Schleicher, E.D., Wagner, E., and Nerlich, A.G.Increased accumulation of the glycoxidation product Nε-(carboxymethyl)lysine in human tissues in diabetes and agingJournal of Clinical Investigation99(3)457-468(1997) 4.Campbell, D.J., Somaratne, J.B., Jenkins, A.J., et al.Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery diseaseCardiovascular Diabetology101-14(2011) 5.Brouwers, O., de Vos-Houben, J.M.J., Niessen, P.M.G., et al.Mild oxidative damage in the diabetic rat heart is attenuated by glyoxalase-1 overexpressionInternational Journal of Molecular Sciences14(8)15724-15739(2013) 6.Schmidt, A.M., Yan, S.D., Yan, S.F., et al.The biology of the receptor for advanced glycation end products and its ligandsBiochimica et Biophysica Acta1498(2-3)99-111(2000) 7.Moy, K.A., Jiao, L., Freedman, N.D., et al.Soluble receptor for advanced glycation end products and risk of liver cancerHepatology57(6)2338-2345(2013)