Hyperglycinemia. V. The Miscible Pool and Turnover Rate of Glycine and the Formation of Serine*

Metabolism of Compounds Labeled with 15N by an Infant with Congenital Hyperammonemia

“…The excretion of 15 N following the administration of 15 N-amino acid and 15 N-ammonium has been investigated in a number of human metabolic states [2,8,11,12,16,19,21,23]. When the intake of protein in the diet is normal, the isotope ingested in these studies rapidly and extensively labels urea in urine ( Fig.…”

“…1) [2,8,11,12,21,23]. For 15 N-amino acid, the general pathway to 15 N-urea involves initial transamination with a-ketoglutaric acid to form glutamic acid [1]. Glutamic acid may then undergo deamination to yield ammonium ion for the synthesis of citrulline via carbamyl phosphate [7] or undergo transamination with oxaloacetic acid to yield aspartic acid which can in turn react with citrulline to form arginino-succinic acid [18].…”

“…Studies of the excretion of 15 N in adult subjects have been compatible with substantial direct incorporation of ingested 15 N-ammonium into urea [21,23]. In premature infants receiving high pro-N in congenital hyperammonemia 253 tern diets, the pattern of excretion of 15 N following the ingestion of 15 N-ammonium chloride suggests little direct incorporation of the nitrogen of ammonium ion into urea [12]. In those infants this nitrogen seems to be incorporated into amino acids and subsequently used, to a large extent, for the synthesis of urea.…”

“…In those infants this nitrogen seems to be incorporated into amino acids and subsequently used, to a large extent, for the synthesis of urea. When nitrogen in the diet is restricted in the premature infant and in other human subjects, the production of 15 N-urea from ingested 15 N-ammonium ion is reduced [12,19,23]. Under these circumstances, the nitrogen of ammonium ion is retained as amino acid nitrogen at the expense of urea production.…”

“…For infants with these disorders, reduction in protein in diet has been associated with symptomatic improvement [3]. The present report deals with the metabolism of compounds labeled with 15 N in an infant with congenital hyperammonemia and reduced activity of hepatic carbamyl phosphate synthetase. She was maintained on a low protein diet, of clinical necessity, throughout these studies.…”