N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia.
OBJECTIVE
The objective of this study was to determine whether N-carbamylglutamate (NCG) reduces plasma levels of ammonia and glutamine and increases the rate of ureagenesis in patients with propionic acidemia (PA).


METHODS
Identical 4-hour studies were performed before and immediately after a 3-day trial of oral NCG in 7 patients with PA. An oral bolus of [(13)C]sodium acetate was administered at the start of each study, and sequential blood samples were obtained to measure [(13)C]urea, ammonia, urea, and amino acids.


RESULTS
With longitudinal mixed-effects linear regression, peak [(13)C]urea increased after treatment with NCG (from 2.2 to 3.8 microM; P < .0005). There were concomitant decreases in mean plasma ammonia (59-43 microM; P < .018) and glutamine (552-331 microM; P < .0005).


CONCLUSIONS
NCG augments ureagenesis and decreases plasma ammonia and glutamine in patients with PA. The drug may serve as an important therapeutic adjunct in the treatment of acute hyperammonemia in this disorder.
Ah Mew
Nicholas
N
Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.
McCarter
Robert
R
Daikhin
Yevgeny
Y
Nissim
Itzhak
I
Yudkoff
Marc
M
Tuchman
Mendel
M
D000284:Administration, Oral; D000293:Adolescent; D000641:Ammonia / Q000097:blood* / Q000378:metabolism; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage*; D005973:Glutamine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D011336:Probability; D056693:Propionic Acidemia / Q000175:diagnosis* / Q000188:drug therapy*; D011446:Prospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome; D014508:Urea / Q000097:blood* / Q000378:metabolism
D005971:Glutamates; D005973:Glutamine; C006895:N-carbamylglutamate; D000641:Ammonia; D014508:Urea