Commentary on Wilcken et al. Asymmetric Dimethylarginine (ADMA) in Vascular and Renal Disease
2007 (English)In: Molecular Genetics and Metabolism, ISSN 1096-7192, E-ISSN 1096-7206, Vol. 91, no 4, 308- p.Article in journal (Refereed) Published
Wilcken and co-workers summarize our current knowledge about the role of asymmetric dimethylarginine (ADMA) as a key regulation of nitric oxide (NO) production, and examine the putative role of ADMA in the development of vascular and organ dysfunction . Impaired NO production is closely associated with vascular dysfunction, especially during states of increased oxidative stress such as smoking, renal dysfunction requiring dialysis, hypertension and diabetes. Vallance et al. early identified increased ADMA levels in patients requiring dialysis, a state commonly associated with vascular dysfunction . ADMA competitively inhibits NOS and competes with arginine for cellular uptake via the cationic amino acid-specific y+-system. Both mechanisms result in reduced NO production. ADMA levels are regulated by the interplay between the production by protein arginine methyltransferases (PRMTs), and the elimination by the metabolizing enzymes dimethylarginine dimethylaminohydrolase (DDAH) and, to a much lesser extent, by urinary excretion. However, as pointed out by the authors, numerous human studies have shown no beneficial effects of arginine supplementation, indicating a level of complexity for the regulation of ADMA levels that is not yet fully understood. The pioneering work by the authors themselves reveals a new mechanism that can explain some of these discrepancies. By showing that arginine directly inhibits DDAH in hepatic (HepG2) cells , they provide important information why arginine administration often fails to improve NO production. The knowledge about the cellular regulation of ADMA is constantly growing and will hopefully result in improved therapeutic strategies, especially for patients with vascular dysfunction due to impaired NO production.
Place, publisher, year, edition, pages
2007. Vol. 91, no 4, 308- p.
Nitric oxide, ADMA, Arginine, Oxidative stress
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-13116DOI: 10.1016/j.ymgme.2007.04.003OAI: oai:DiVA.org:uu-13116DiVA: diva2:40886