Identification of N-beta-L-aspartyl-L-phenylalanine as a normal constituent of human plasma and urine.
A new beta-aspartyl dipeptide, N-beta-L-aspartyl-L-phenylalanine (beta-AP), has been isolated and identified in urine and plasma from normal human volunteers. beta-AP was isolated from urine samples by high performance liquid chromatography (HPLC). Its identity and stereochemistry were demonstrated by HPLC and gas chromatography/mass spectrometry (GC-MS). The mean urinary beta-AP concentration in the subjects was 0.63 +/- 0.14 microgram/mg creatinine when averaged over two consecutive days of urine collection. Daily beta-AP excretion, determined from two 24-h urine samples collected from five individuals, was 801 +/- 117 micrograms/d (2.7 mumol/d). No diurnal rhythm was evident within the 24-h collection periods. beta-AP was also isolated from human plasma by HPLC and identified by GC-MS. Plasma from subjects contained approximately 5 ng beta-AP/ml. Furthermore, beta-AP was formed when asparagine and phenylalanine were incubated with an enzyme extract from human kidney. Thus, at least some of the beta-AP present in humans, and presumably other beta-aspartyl dipeptides as well, appears to be synthesized endogenously.
Burton
E G
EG
Department of Drug Metabolism, G. D. Searle & Co., Skokie, IL 60077.
Schoenhard
G L
GL
Hill
J A
JA
Schmidt
R E
RE
Hribar
J D
JD
Kotsonis
F N
FN
Oppermann
J A
JA
D001224:Aspartic Acid / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm; D004151:Dipeptides / Q000096:biosynthesis / Q000097:blood / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D013058:Mass Spectrometry; D009994:Osmolar Concentration; D010649:Phenylalanine / Q000378:metabolism / Q000652:urine; D012016:Reference Values
D004151:Dipeptides; C045207:aspartyl-phenylalanine; D001224:Aspartic Acid; D010649:Phenylalanine