ESSENTIAL CARBAMOYL-AMINO ACIDS FORMED IN-VIVO IN PATIENTS WITH END-STAGE RENAL-DISEASE MANAGED BY CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS - ISOLATION, IDENTIFICATION, AND QUANTITATION

Carbamoyl-amino acids (C-AA) are formed by reaction of amino acids wit h 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 derivatiza tion. Free-amino acids (F-AA) but no C-AA were found in the postabsorp tive plasma of eight normal persons with blood urea nitrogen (BUN) lev els ranging from 9 to 16 mg/dl, In a longitudinal study of postprandia l plasma (n = 43), essential amino acids, both C-AA and F-AA, were iso lated and quantified by reverse-phase high-pressure liquid chromatogra phy in six patients with end-stage renal disease who were managed by c ontinuous ambulatory peritoneal dialysis. The mean BUN was 61 mg/dl (r ange, 36 to 79 mg/dl). In uremia, removal of F-AA from the essential a mino 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 am ino acid, the Cls were as follows: leucine, 4; valine, 3.3; isoleucine , 11.4; threonine, 9; lysine, 2; methionine, 3.5; histidine, 3.5; phen ylalanine, 0.5; and tyrosine, 1.3. Carbamoylation of F-AA may account, in part, for the lower than normal levels of F-AA iri patients with u remia. The derivatized amino group of C-AA interferes with formation o f a peptide bond in protein synthesis, which requires an underivatized amino acid. A decrease in the F-AA pool available for protein synthes is and anabolism in the presence of C-AA may provide additional contri buting factors for the development of malnutrition in uremia.