Kinetics of ammonia metabolism in vivo.

The studies of Schoenheimer and his colleagues (1) amply demonstrated that N16, introduced into the animal as ammonia or an cy-amino acid, may later be found not only in urea but in the amino acids of tissue protein. Particularly rich were glutamic and aspartic acids and the amide nitrogen of glutamine and asparagine. These findings, coupled with the great activity of hepatic transaminases and glutamic dehydrogenase and the relatively weak activity of hepatic L-amino acid oxidases when assayed in vitro (2), led to the concept that deamination of L-amino acids is accomplished by the consecutive action of specific transaminases and glutamic dehydrogenase. Incorporation of administered NH3-N16 into amino acids has been considered to occur by reversal of the process. The collective actions of glutamic dehydrogenase, glutamine synthetase, and carbamyl phosphate synthesis have been suggested (3) as the explanation of the extremely’low concentration of ammonia in animal tissue (4). These concepts have not been subjected to a direct experimental test in vivo. Although several reactions have been observed in which the amide nitrogen of glutamine is transferred to various acceptors (5-9), the metabolic role of the large amounts of glutamine in animal tissues is but poorly understood. There have been repeated suggestions that glutamine, rather than ammonia, may be specifically employed for urea synthesis; the status of this problem has recently been reviewed (3). In the present studies NHI, glutamine, Dand L-leucine, labeled with N16, have been given intravenously to rats, and the N16 content of the non-protein nitrogenous components of liver and other tissues has been determined after various time intervals in the hope that the data so obtained might elucidate the problems cited above.