Studies on the in vivo Metabolism of α- and β-Aspartylglycine-1-C^14*

Abstract

Human subjects were given 4-mg intravenous doses of a-~-aspartylglycine-l-C~~, P-Laspartylglycine-1-C 4, or an equivalent molar amount of free g1y~ine-l-C'~ and unlabeled aspartic acid. Much more radioactivity appeared in the expired carbon dioxide, in the urinary hippuric acid, and in the glycine and serine of plasma protein when the a rather than the p peptide was given. The results with free glycine and the a peptide were similar. When the p peptide was administered most of the radioactivity promptly appeared in the urine in the same chemical form but mixed with a larger quantity of endogenous p-aspartylglycine.The accompanying report from this laboratory (Buchanan et d., 1962) describes the isolation and identification of a number of B-aspartyl and yglutamyl oligopeptides from human urine. The most abundant of these, p-aspartylglycine, was shown not to arise by isomerization of a-aspartylglycine (John and Young, 1954;Swallow and Abraham, 1958; Byrant et al., 1959) during the isolation procedure, and it is likely that the other @-aspartyl oligopeptides found are actually excreted in the fl form. The present paper reports *Supported in part by Grant A-1277 from the United States Public Health Service. Preliminary reports (Haley et al., 1961; Buchanan at al., 1961) have appeared. studies on the metabolic fates of synthetic aand 8-aspartylglycines given intravenously to human subjects. The results support a hypothesis (Buchanan et aZ., 1962) that may explain the presence of P-aspartyl peptides in urine. METHODSThe wand P-L-aspartylglycines were prepared from carbobenzoxy-L-aspartic acid and glycine-l-C14 by a slight modification of the procedure of LeQuesne and Young (1952), separated chromatographically, and recrystallized from alcohol !Buchanan et d., 1962). The specific radioactivity of crystalline peptides was 2.5 pc per mg.

Confirmation of d-aspartic acid in the novel dipeptide β-aspartylglycine isolated from tissue extract of Aplysia kurodai

“…analysis can be attributed to incomplete separation from tissue extract and/or to seasonal variation. /J-Asp-Gly has been identified previously in human urine (Buchanan et al, 1962;Gejyo et al, 1978), in collagen (Pisano et al, 1966), in caecal contents of mammals (Welling & Groen, 1978;Welling, 1982) and also in tissues of Aplysia californica (McCaman & Stetzler, 1984). However, there is no information in these reports on the configuration of aspartic acid of /,-Asp-Gly.…”

β-Aspartyl Peptides in Enzymatic Hydrolysates of Protein*

“…There was no increase in the ß-aspartylglycine content of human or bovine tendon collagen with aging in vivo nor of lysozyme with aging in vitro. The data suggest that, in intact proteins, ßaspartyl linkages do not form spontaneously from aaspartyl or asparaginyl linkages. products, less readily cleaved by tissue peptidases and more susceptible to renal excretion than a-aspartyl peptides, was supported by results of experiments in which human subjects were given glycine-labeled Asp-Gly or Asp(Gly), or labeled glycine intravenously (Buchanan et al, 1962b). Most of the ß peptide was quickly excreted, while the metabolic pattern of the injected a peptide was similar to that found when free glycine was administered.…”

β-Aspartylglycine, a substance unique to caecal contents of germ-free and antibiotic-treated mice

“…In human urine, fl-aspartyl peptides are commonly present (Buchanan et al, 1962a,b). Buchanan et al (1962b) and Dorer et al (1966) provided evidence that f-aspartylglycine in urine is largely endogenous and results from protein catabolism. The remaining part is derived more directly from protein in the diet.…”