N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia.

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  • Additional Information
    • Source:
      Publisher: American Academy of Pediatrics Country of Publication: United States NLM ID: 0376422 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-4275 (Electronic) Linking ISSN: 00314005 NLM ISO Abbreviation: Pediatrics Subsets: MEDLINE
    • Publication Information:
      Publication: Elk Grove Village Il : American Academy of Pediatrics
      Original Publication: Springfield, Ill., Thomas.
    • Subject Terms:
      Ammonia/*blood ; Glutamates/*administration & dosage ; Glutamine/*blood ; Propionic Acidemia/*diagnosis ; Propionic Acidemia/*drug therapy ; Urea/*blood; Administration, Oral ; Adolescent ; Ammonia/metabolism ; Blood Chemical Analysis ; Child ; Child, Preschool ; Confidence Intervals ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Glutamine/metabolism ; Humans ; Infant ; Male ; Probability ; Prospective Studies ; Risk Assessment ; Treatment Outcome ; Urea/metabolism
    • Abstract:
      Objectives: 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.
    • References:
      Neurology. 1984 Apr;34(4):550-3. (PMID: 6422325)
      Pediatr Res. 1976 Jul;10(7):683-6. (PMID: 934734)
      Mol Genet Metab. 2004 Apr;81 Suppl 1:S45-51. (PMID: 15050973)
      J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S219-22. (PMID: 18338235)
      J Inherit Metab Dis. 1997 Nov;20(6):839-40. (PMID: 9427158)
      J Clin Invest. 1979 Dec;64(6):1544-51. (PMID: 500823)
      J Inherit Metab Dis. 2005;28(2):241-4. (PMID: 15877213)
      J Pediatr. 1980 Dec;97(6):893-900. (PMID: 7441417)
      Pediatr Res. 1986 Jan;20(1):49-52. (PMID: 3511440)
      Eur J Pediatr. 2010 Jan;169(1):133-4. (PMID: 19680687)
      Am J Hum Genet. 1994 Jul;55(1):51-8. (PMID: 8023851)
      Mol Genet Metab. 2003 Aug;79(4):303-4. (PMID: 12948747)
      Mol Genet Metab. 2009 Dec;98(4):325-30. (PMID: 19660971)
      Isotopes Environ Health Stud. 1999;35(1-2):19-37. (PMID: 10902535)
      N Engl J Med. 1982 Jun 10;306(23):1387-92. (PMID: 7078580)
      Neonatology. 2010;97(3):286-90. (PMID: 19887858)
      J Inherit Metab Dis. 1998 Dec;21(8):867-8. (PMID: 9870213)
      Adv Pediatr. 1996;43:127-70. (PMID: 8794176)
      Mol Genet Metab. 2008 Aug;94(4):397-402. (PMID: 18562231)
      Pediatr Res. 2008 Aug;64(2):213-7. (PMID: 18414145)
      J Clin Invest. 1980 Sep;66(3):484-92. (PMID: 7400325)
      N Engl J Med. 1981 Feb 26;304(9):543. (PMID: 7453791)
      J Pediatr. 2004 Oct;145(4):552-4. (PMID: 15480384)
      Pediatr Res. 1982 Jan;16(1):5-7. (PMID: 7070876)
      J Inherit Metab Dis. 1995;18(1):61-5. (PMID: 7623444)
      J Biol Chem. 1958 Feb;230(2):1013-21. (PMID: 13525417)
    • Grant Information:
      R01 DK064913 United States DK NIDDK NIH HHS; R01 DK047870-16 United States DK NIDDK NIH HHS; R01 DK064913-09 United States DK NIDDK NIH HHS; R01 HD058567-01 United States HD NICHD NIH HHS; U54 HD061221 United States HD NICHD NIH HHS; R01 DK047870-15 United States DK NIDDK NIH HHS; R01 DK053761 United States DK NIDDK NIH HHS; R01DK47870 United States DK NIDDK NIH HHS; R01 HD058567-03 United States HD NICHD NIH HHS; P01 NS054900 United States NS NINDS NIH HHS; R01 DK047870-14 United States DK NIDDK NIH HHS; U54 RR019453 United States RR NCRR NIH HHS; U54RR-019453 United States RR NCRR NIH HHS; R01 HD058567-02 United States HD NICHD NIH HHS; R01DK64913 United States DK NIDDK NIH HHS; P30 HD026979 United States HD NICHD NIH HHS; R01 DK047870 United States DK NIDDK NIH HHS; R01HD058567 United States HD NICHD NIH HHS; R01 DK064913-08 United States DK NIDDK NIH HHS; NS054900 United States NS NINDS NIH HHS; RR024134 United States RR NCRR NIH HHS; R01 HD058567 United States HD NICHD NIH HHS; R01 DK064913-07 United States DK NIDDK NIH HHS; P01HD26979 United States HD NICHD NIH HHS; R01 DK047870-13 United States DK NIDDK NIH HHS; UL1 RR024134 United States RR NCRR NIH HHS
    • Accession Number:
      0 (Glutamates)
      0RH81L854J (Glutamine)
      1188-38-1 (N-carbamylglutamate)
      7664-41-7 (Ammonia)
      8W8T17847W (Urea)
    • Publication Date:
      Date Created: 20100623 Date Completed: 20100728 Latest Revision: 20220318
    • Publication Date:
      20240829
    • Accession Number:
      PMC3297024
    • Accession Number:
      10.1542/peds.2010-0008
    • Accession Number:
      20566609