Competitive metabolism of L-arginine:arginase as a therapeutic target in asthma

作     者：Jennifer M.Bratt Amir A.Zeki Jerold A.Last Nicholas J.Kenyon 

作者机构：Department of Internal MedicineDivision of Pulmonary and Critical Care and Sleep MedicineUniversity of California 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2011年第25卷第5期

页      面：299-308页

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the following grants:National Institute of Environmental Health Sciences funded training program in Environmental Health Sciences (No.T32 ES007058-33) to Jennifer M.Bratt,CTSC K12 Award (No.UL1RR024146) KL2RR024144 to Amir A.Zeki the American Asthma Foundation to Nicholas J.Kenyon 

主　　题：nitric oxide L-arginine arginase nor-NOHA nitrosation nitric oxide synthase 

摘      要：Exhaled breath nitric oxide （NO） is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase （NOS） and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential tox- icity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics.