期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2010
卷号：46
期号：2
页码：177-185
DOI：10.3164/jcbn.09-104
出版社：The Society for Free Radical Research Japan
摘要：N ω-Carboxymethyl-arginine (CMA), N ω-carboxyethyl-arginine (CEA) and N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) have been identified as L-arginine-derived advanced glycation end products (AGEs) formed by non-enzymatic reactions between reducing sugars such as glucose and amino groups in proteins. These AGEs are structurally analogous to endogenous inhibitors of nitric oxide synthases (NOS) including N G-monomethyl-L-arginine (L-NMMA) and asymmetric N G, N G-dimethyl-L-arginine (ADMA). Increased plasma levels of these NOS inhibitors, and thus impaired generation of NO in vivo has been associated with the pathogenesis of vascular complications such as kidney failure and atherosclerosis. For these reasons we examined whether L-arginine-derived AGEs inhibit the activities of three L-arginine metabolizing enzymes including three isoforms of NOS (endothelium, neuronal and inducible NOS), dimethylarginine dimethylaminohydrolase (DDAH) that catalyzes the hydrolytic degradation of L-NMMA and ADMA to L-citrulline, and arginase that modulates intracellular L-arginine bioavailability. We found that AGEs inhibited the in vitro activities of endothelium type NOS weakly (IC50 values of CMA, CEA and MG-H1 were 830, 3870 and 1280 μM, respectively) and were also potential endogenous inhibitors for arginase (IC50 values of CMA and CML were 1470 and 1060 μM), but were poor inhibitors for DDAH. These results suggest that the tested L-arginine- and L-lysine-derived AGEs appear not to impair NO biosynthesis directly.
关键词：advanced glycation end products;Nω-carboxymethyl-arginine;nitric oxide synthase;dimethylarginine dimethylaminohydrolase;arginase
