Isolation and Identification of N,N- and N,N' -Dimethylarginine, Nε-Mono-, Di-, and Trimethyllysine, and Glucosylgalactosyl- and Galactosyl-δ-hydroxylysine from Human Urine

Abstract 1. Eight different substances were isolated in crystalline forms by ion exchange chromatography of the aliphatic basic amino acid fraction of human urine. 2. Structures of guanidino-N,N-dimethylarginine and guanidino-N,N'-dimethylarginine were assigned for two substances by analyses of the degradation products, elemental compositions, and nuclear magnetic resonance spectra. The identities of the compounds were confirmed by synthesis followed by comparison of infrared and nuclear magnetic resonance spectra and of chromatographic properties with those of the isolated compounds. The concentrations of these two compounds in human urine are higher than that of arginine. Their natural occurrence has not been reported previously. 3. Three compounds, Ne-methyl-, Ne,Ne-dimethyl-, and Ne,Ne,Ne-trimethyllysine, were identified by elementary analyses and syntheses. Occurrence of the last two compounds in free state in nature has not been reported previously. 4. Two compounds, glucosylgalactosyl- and galactosyl-δ-hydroxylysine, whose occurrence in human urine has been reported previously, were isolated as crystals for the first time. 5. The concentrations of these N-methyl derivatives of lysine and arginine in the urine were not changed by oral loading of either lysine or arginine. Protein-free diet did not affect the amounts of these compounds in urine. The possibility that these compounds are derived from tissue proteins in which lysine and arginine residues are methylated was discussed.