title: Alterations of the arginine metabolome in asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathobiology, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lara
authors.forename: Sumita B
authors.initials: SB
authors.lastname: Khatri
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Wang
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Weiling
authors.initials: W
authors.lastname: Xu
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
authors.forename: Melanie
authors.initials: M
authors.lastname: Bodine
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Levison
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hammel
authors.forename: Eugene
authors.initials: E
authors.lastname: Bleecker
authors.forename: William
authors.initials: W
authors.lastname: Busse
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar
authors.initials: N
authors.lastname: Jarjour
authors.forename: Wendy
authors.initials: W
authors.lastname: Moore
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Sally
authors.initials: S
authors.lastname: Wenzel
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000328:Adult; D001119:Arginase / Q000097:blood / Q000378:metabolism*; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001682:Biological Availability; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D013147:Spirometry
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase