Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: Isolation, identification, and quantitation

Abstract

Carbamoyl-amino acids (C-AA) are formed by reaction of amino acids with cyanate, which is spontaneously formed from urea at body temperature and pH. In vivo derivatized C-AA are not measured by the usual amino acid analysis methods, which require a free amino group for derivatization. Free-amino acids (F-AA) but no C-AA were found in the postabsorptive plasma of eight normal persons with blood urea nitrogen (BUN) levels ranging from 9 to 16 mg/dl. In a longitudinal study of postprandial plasma (n = 43), essential amino acids, both C-AA and F-AA, were isolated and quantified by reverse-phase high-pressure liquid chromatography in six patients with end-stage renal disease who were managed by continuous ambulatory peritoneal dialysis. The mean BUN was 61 mg/dl (range, 36 to 79 mg/dl). In uremia, removal of F-AA from the essential amino acid pool to form C-AA is measured by the ratio of C-AA to F-AA (carbamoylation index (CI)). Using the mean value for each essential amino acid, the CIs were as follows: leucine, 4; valine, 3.3; isoleucine, 11.4; threonine, 9; lysine, 2; methionine, 3.5; histidine, 3.5; phenylalanine, 0.5; and tyrosine, 1.3. Carbamoylation of F-AA may account, in part, for the lower than normal levels of F-AA in patients with uremia. The derivatized amino group of C-AA interferes with formation of a peptide bond in protein synthesis, which requires an underivatized amino acid. A decrease in the F-AA pool available for protein synthesis and anabolism in the presence of C-AA may provide additional contributing factors for the development of malnutrition in uremia.