Alterations of the arginine metabolome in asthma.

Rationale: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation.Objectives: We hypothesized that arginine (Arg) bioavailability would be associ...

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Publicado en:American Journal of Respiratory & Critical Care Medicine Vol. 178; no. 7; pp. 673 - 682
Autores principales: Lara A, Khatri SB, Wang Z, Comhair SA, Xu W, Dweik RA, Bodine M, Levison BS, Hammel J, Bleecker E, Busse W, Calhoun WJ, Castro M, Chung KF, Curran-Everett D, Gaston B, Israel E, Jarjour N, Moore W, Peters SP
Formato: research Journal Article
Publicado: Oxford University Press / USA Oct2008
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2008
      vid: 178
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      pub: Oxford University Press / USA
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        atl: Alterations of the arginine metabolome in asthma.
      aug:
        au:
          Lara A
          Khatri SB
          Wang Z
          Comhair SA
          Xu W
          Dweik RA
          Bodine M
          Levison BS
          Hammel J
          Bleecker E
          Busse W
          Calhoun WJ
          Castro M
          Chung KF
          Curran-Everett D
          Gaston B
          Israel E
          Jarjour N
          Moore W
          Peters SP
      sug:
        subj:
          Arginine Metabolism
          Asthma Metabolism
          Hydrolases Metabolism
          Nitric Oxide Metabolism
          Adult
          Arginine Blood
          Asthma Physiopathology
          Biological Availability
          Breath Tests
          Case Control Studies
          Female
          Hydrolases Blood
          Male
          Spirometry
          Human
          Adult: 19-44 years
          Female
          Male
      ab: Rationale: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation.Objectives: We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity.Methods: Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated.Measurements and Main Results: Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma.Conclusions: Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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