title: N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia.
abstract: 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.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ah Mew
authors.forename: Robert
authors.initials: R
authors.lastname: McCarter
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Daikhin
authors.forename: Itzhak
authors.initials: I
authors.lastname: Nissim
authors.forename: Marc
authors.initials: M
authors.lastname: Yudkoff
authors.forename: Mendel
authors.initials: M
authors.lastname: Tuchman
mesh_terms: 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
chemical_list: D005971:Glutamates; D005973:Glutamine; C006895:N-carbamylglutamate; D000641:Ammonia; D014508:Urea