Literature DB >> 20566609

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

Nicholas Ah Mew1, Robert McCarter, Yevgeny Daikhin, Itzhak Nissim, Marc Yudkoff, Mendel Tuchman.   

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.

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Year:  2010        PMID: 20566609      PMCID: PMC3297024          DOI: 10.1542/peds.2010-0008

Source DB:  PubMed          Journal:  Pediatrics        ISSN: 0031-4005            Impact factor:   7.124


  26 in total

1.  Effect of propionic acid on fatty acid oxidation and ureagenesis.

Authors:  A M Glasgow; H P Chase
Journal:  Pediatr Res       Date:  1976-07       Impact factor: 3.756

2.  N-acetylglutamate synthetase deficiency: a disorder of ammonia detoxication.

Authors:  C Bachmann; S Krähenbühl; J P Colombo; G Schubiger; K H Jaggi; O Tönz
Journal:  N Engl J Med       Date:  1981-02-26       Impact factor: 91.245

3.  Valproic acid-induced hyperammonemia in mentally retarded adults.

Authors:  C A Williams; S Tiefenbach; J W McReynolds
Journal:  Neurology       Date:  1984-04       Impact factor: 9.910

4.  Treatment of hyperammonemic coma caused by inborn errors of urea synthesis.

Authors:  M L Batshaw; S W Brusilow
Journal:  J Pediatr       Date:  1980-12       Impact factor: 4.406

5.  Failure of the normal ureagenic response to amino acids in organic acid-loaded rats. Proposed mechanism for the hyperammonemia of propionic and methylmalonic acidemia.

Authors:  P M Stewart; M Walser
Journal:  J Clin Invest       Date:  1980-09       Impact factor: 14.808

Review 6.  Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism.

Authors:  Charles A Stanley
Journal:  Mol Genet Metab       Date:  2004-04       Impact factor: 4.797

7.  N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria.

Authors:  Boris Gebhardt; Stefan Vlaho; Doris Fischer; Adrian Sewell; Hansjosef Böhles
Journal:  Mol Genet Metab       Date:  2003-08       Impact factor: 4.797

8.  Glycine cleavage system in ketotic hyperglycinemia: a reduction of H-protein activity.

Authors:  K Hayasaka; K Narisawa; T Satoh; H Tateda; K Metoki; K Tada; K Hiraga; T Aoki; T Kawakami; H Akamatsu; N Matsuo
Journal:  Pediatr Res       Date:  1982-01       Impact factor: 3.756

9.  Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion.

Authors:  M L Batshaw; S Brusilow; L Waber; W Blom; A M Brubakk; B K Burton; H M Cann; D Kerr; P Mamunes; R Matalon; D Myerberg; I A Schafer
Journal:  N Engl J Med       Date:  1982-06-10       Impact factor: 91.245

10.  Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia.

Authors:  F X Coude; L Sweetman; W L Nyhan
Journal:  J Clin Invest       Date:  1979-12       Impact factor: 14.808

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  25 in total

Review 1.  Acute management of propionic acidemia.

Authors:  Kimberly A Chapman; Andrea Gropman; Erin MacLeod; Kathy Stagni; Marshall L Summar; Keiko Ueda; Nicholas Ah Mew; Jill Franks; Eddie Island; Dietrich Matern; Loren Pena; Brittany Smith; V Reid Sutton; Tiina Urv; Charles Venditti; Anupam Chakrapani
Journal:  Mol Genet Metab       Date:  2011-09-24       Impact factor: 4.797

2.  N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy.

Authors:  Sandra K Heibel; Nicholas Ah Mew; Ljubica Caldovic; Yevgeny Daikhin; Marc Yudkoff; Mendel Tuchman
Journal:  Hum Mutat       Date:  2011-09-09       Impact factor: 4.878

3.  Nutritional and Pharmacological Management during Chemotherapy in a Patient with Propionic Acidaemia and Rhabdomyosarcoma Botryoides.

Authors:  E Martín-Hernández; P Quijada-Fraile; L Oliveros-Leal; Mt García-Silva; C Pérez-Cerdá; M Baro-Fernández; V Pérez-Alonso; Jl Vivanco
Journal:  JIMD Rep       Date:  2012-03-21

4.  Short-term outcome of propionic aciduria treated at presentation with N-carbamylglutamate: a retrospective review of four patients.

Authors:  Sébastien Lévesque; Marie Lambert; Aspasia Karalis; Serge Melancon; Laura Russell; Nancy Braverman
Journal:  JIMD Rep       Date:  2011-09-06

Review 5.  Treatment strategies for acute metabolic disorders in neonates.

Authors:  Sarar Mohamed
Journal:  Sudan J Paediatr       Date:  2011

6.  Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes.

Authors:  Dashuang Shi; Gengxiang Zhao; Nicholas Ah Mew; Mendel Tuchman
Journal:  Mol Genet Metab       Date:  2016-12-08       Impact factor: 4.797

7.  Expansion of the Phenotypic Spectrum of Propionic Acidemia with Isolated Elevated Propionylcarnitine.

Authors:  Gerarda Cappuccio; Paldeep S Atwal; Taraka R Donti; Kiki Ugarte; Nadia Merchant; William J Craigen; V Reid Sutton; Sarah H Elsea
Journal:  JIMD Rep       Date:  2016-11-30

Review 8.  Recurrent encephalopathy: NAGS (N-acetylglutamate synthase) deficiency in adults.

Authors:  A Cartagena; A N Prasad; C A Rupar; M Strong; M Tuchman; N Ah Mew; C Prasad
Journal:  Can J Neurol Sci       Date:  2013-01       Impact factor: 2.104

9.  Recapitulation of metabolic defects in a model of propionic acidemia using patient-derived primary hepatocytes.

Authors:  Kimberly A Chapman; Maria S Collado; Robert A Figler; Stephen A Hoang; Allison J Armstrong; Wanxing Cui; Michael Purdy; Michael B Simmers; Nada A Yazigi; Marshall L Summar; Brian R Wamhoff; Ajit Dash
Journal:  Mol Genet Metab       Date:  2015-12-24       Impact factor: 4.797

Review 10.  Methylmalonic and propionic acidemias: clinical management update.

Authors:  Jamie L Fraser; Charles P Venditti
Journal:  Curr Opin Pediatr       Date:  2016-12       Impact factor: 2.856

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