Identification of N-omega-carboxymethylarginine as a novel acid-labile advanced glycation end product in collagen

Collagen undergoes continuous non-enzymatic glycation during its long life period. The products resulting from the glycation reaction, so-called advan ced glycation end products (AGEs), were regarded as potential pathogens of various diseases such as diabetic complications. Although several AGEs were identified from acid hydrolysates of glycated collagen, the major AGE(s) r esponsible for the diseases have not yet been fully characterized. Moreover , acid-labile constituents were decomposed during acid hydrolysis. To inves tigate these AGEs, we used the enzymatic hydrolysis method [Bensusan, Dixit and McKnight (1971) Biochim. Biophys. Acta 251, 100-108]. As a result, an acid-labile unknown compound was discovered from the digested glycated coll agen. We identified this compound as N-omega-carboxymethyl-arginine (CMA) b y matrix-assisted laster-desorption ionization-MS and NMR. CMA gradually in creased in collagen during incubation with glucose and the yield reached ab out 8 mol/mol of collagen, which is 100 times higher than that of pentosidi ne. This result suggests that CMA is a major AGE in collagen.