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Identification of N(omega)-carboxymethylarginine as a novel acid-labileadvanced glycation end product in collagen.

ABSTRACT: Collagen undergoes continuous non-enzymatic glycation during its long life period. The products resulting from the glycation reaction, so-called advanced 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) responsible for the diseases have not yet been fully characterized. Moreover, acid-labile constituents were decomposed during acid hydrolysis. To investigate 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 collagen. We identified this compound as N(omega)-carboxymethylarginine (CMA) by matrix-assisted laster-desorption ionization-MS and NMR. CMA gradually increased in collagen during incubation with glucose and the yield reached about 8 mol/mol of collagen, which is 100 times higher than that of pentosidine. This result suggests that CMA is a major AGE in collagen.

SUBMITTER: Iijima K

PROVIDER: S-EPMC1220926 | biostudies-other | 2000 Apr

REPOSITORIES: biostudies-other

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Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

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Identification of N(omega)-carboxymethylarginine as a novel acid-labileadvanced glycation end product in collagen.

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