Decreased arginine bioavailability and increased serum arginase activity in asthma.
Recent studies suggest that a nitric oxide (NO) deficiency and elevated arginase activity may play a role in the pathogenesis of asthma. Although much attention has been directed toward measurements of exhaled NO in asthma, no studies to date have evaluated levels of plasma arginase or arginine, the substrate for NO production, in patients with asthma. This study, therefore, measured amino acid levels, arginase activity, and nitric oxide metabolites in the blood of patients with asthma, as well as NO in exhaled breath. Although levels of virtually all amino acids were reduced, patients with asthma exhibited a striking reduction in plasma arginine levels compared with normal control subjects without asthma (45 +/- 22 vs. 94 +/- 29 microM, p < 0.0001), and serum arginase activity was elevated (1.6 +/- 0.8 vs. 0.5 +/- 0.3 micromol/ml/hour, asthma vs. control, p < 0.0001). High arginase activity in patients with asthma may contribute to low circulating arginine levels, thereby limiting arginine bioavailability and creating a NO deficiency that induces hyperreactive airways. Addressing the alterations in arginine metabolism may result in new strategies for treatment of asthma.
Morris
Claudia R
CR
Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, Oakland, CA 94609, USA. claudiamorris@comcast.net
Poljakovic
Mirjana
M
Lavrisha
Lisa
L
Machado
Lorenzo
L
Kuypers
Frans A
FA
Morris
Sidney M
SM
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000097:blood; D001119:Arginase / Q000097:blood*; D001120:Arginine / Q000493:pharmacokinetics*; D001249:Asthma / Q000097:blood* / Q000201:enzymology* / Q000628:therapy; D001682:Biological Availability; D001944:Breath Tests; D002648:Child; D002675:Child, Preschool; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis
D000596:Amino Acids; D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase