title: Alterations of the arginine metabolome in sickle cell disease: a growing rationale for arginine therapy.
abstract: Low global arginine bioavailability (GAB) is associated with numerous complications of SCD including early mortality. Mechanisms of arginine dysregulation involve a complex paradigm of excess activity of the arginine-consuming enzyme arginase, elevated levels of asymmetric dimethylarginine, altered intracellular arginine transport, and nitric oxide synthase dysfunction. Restoration of GAB through exogenous supplementation is therefore, a promising therapeutic target. Studies of arginine therapy demonstrate efficacy in treating patients with leg ulcers, pulmonary hypertension risk, and pain. Co-administration with hydroxyurea increases levels of nitrite and fetal hemoglobin. Addressing the alterations in the arginine metabolome may result in new strategies for treatment of SCD.
authors.affiliation: Division of Emergency Medicine, Department of Pediatrics, Emory-Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, 1645 Tullie Circle Northeast, Atlanta, GA 30329, USA. Electronic address: claudia.r.morris@emory.edu.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Morris
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000378:metabolism*; D000986:Antisickling Agents / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005319:Fetal Hemoglobin / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D055442:Metabolome; D016896:Treatment Outcome
chemical_list: D000986:Antisickling Agents; D005319:Fetal Hemoglobin; D001120:Arginine; D006918:Hydroxyurea
keywords: Arginase; Arginine; Hemolysis; Nitric oxide; Sickle cell disease; Vasoocclusive pain episodes