title: Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.
abstract: Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, The Children's Hospital at King Fahad Medical City and Faculty of Medicine at King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Ayman W
authors.initials: AW
authors.lastname: El-Hattab
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Emrick
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sirisak
authors.initials: S
authors.lastname: Chanprasert
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Craigen
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: fscaglia@bcm.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
mesh_terms: D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D002956:Citrulline / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D017241:MELAS Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000172:deficiency* / Q000378:metabolism
chemical_list: D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine
keywords: Lactic acidosis; Myopathy; Nitric oxide (NO); Nitric oxide synthase (NOS); Stroke-like episodes