L-ARGININE INHIBITS IN-VITRO NONENZYMATIC GLYCATION AND ADVANCED GLYCOSYLATED END-PRODUCT FORMATION OF HUMAN SERUM-ALBUMIN

L-Arginine (Arg) has a structure similar to that of aminoguanidine (AG ) and may inhibit glycation and advanced glycosylated end product (AGE ) formation. Human serum albumin (HSA) (100 mg/ml) was incubated for 2 weeks with glucose (200 mM) at 37 degrees C or with glucose and equim olar concentrations of Arg, N-alpha-acetyl Arg, or AG with or without 25 mM diethylenetriaminepentaacetic acid (DTPA). In the absence of DTP A, electrospray ionization mass spectrometry showed a 70% reduction of covalently bound glucose in the presence of Arg and a 30% reduction w ith AG. Digestibility by trypsin of HSA incubated with glucose and Arg was similar to that of HSA incubated alone. This suggests less covale nt modification of HSA in the presence of Arg as compared with the abs ence of Arg. When incubations contained DTPA, autoradiography showed l ess C-14 labeling of HSA subunits in the presence of Arg and AG. When the alpha-amino group of Arg was blocked with an acetyl group, labelin g was similar to that of HSA incubated with glucose, suggesting involv ement of the alpha-amino group in the inhibition. Fluorescence of HSA at ex(370) and em(440) was reduced with Arg, but AG was more effective than Arg. These results suggest that Arg, like AG, can inhibit glycat ion and AGE formation.