title: L-homoarginine and cardiovascular disease.
abstract: OBJECTIVE
  An increasing number of reports indicate that low levels of the endogenous amino acid L-homoarginine are linked to cardiovascular disease. In this article, we review the current findings regarding L-homoarginine metabolism and (patho-)physiology with a focus on its clinical impact.
  
  
  RESULTS
  Recent clinical and epidemiological studies revealed a strong association of low circulating L-homoarginine with cardiovascular outcomes and mortality. Human and murine studies identified L-arginine:glycine amidinotransferase (AGAT) as the responsible enzyme for endogenous L-homoarginine formation, suggesting a further important function of AGAT apart from its involvement in creatine and energy metabolism. Further studies related L-homoarginine to smoking and hypertension, and metabolic phenotypes.
  
  
  CONCLUSIONS
  AGAT deficiency results in diminished intracellular energy stores (i.e., ATP and phosphocreatine), as well as a lack of L-homoarginine, and has been linked to an improved metabolic risk profile, but also to impaired cardiac and cerebrovascular function. L-homoarginine's structural similarity to L-arginine suggested physiological interference with L-arginine pathways (e.g., nitric oxide). Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease.
authors.affiliation: aInstitute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf bDZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck cDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Chi-un
authors.initials: CU
authors.lastname: Choe
mesh_terms: D000579:Amidinotransferases / Q000172:deficiency*; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D002658:Developmental Disabilities / Q000150:complications; D004734:Energy Metabolism; D006709:Homoarginine / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000150:complications*; D013064:Speech Disorders / Q000150:complications*
chemical_list: D006709:Homoarginine; D000579:Amidinotransferases