title: L-arginine regulates asymmetric dimethylarginine metabolism by inhibiting dimethylarginine dimethylaminohydrolase activity in hepatic (HepG2) cells.
abstract: An increase in circulating asymmetric dimethylarginine (ADMA) and a decreased L-arginine/ADMA ratio are associated with reduced endothelial nitric oxide (NO) production and increased risk of vascular disease. We explored relations between ADMA, L-arginine and dimethylarginine dimethylaminohydrolase (DDAH) in liver (HepG2) cells. DDAH is the principle enzyme for the metabolism of ADMA. HepG2 cells metabolised 44.8 nmol/h of ADMA per 3.6 x 10(6) cells in the absence of L-arginine. The metabolism of ADMA at physiological (1mu mol/l, p < 0.01) and at pathological (100mumol/l, p < 0.01) levels was inhibited dose-dependently by L-arginine (0-400mumol/l) in cultured HepG2 cells and increased intracellular ADMA (p = 0.039). L-arginine competitively inhibited DDAH enzyme activity to 5.6 +/- 2.0% of the untreated level (p < 0.01). We conclude that L-arginine regulates ADMA metabolism dose-dependently by competing for DDAH thus maintaining the metabolic balance of L-arginine and ADMA, and endothelial NO homeostasis.
authors.affiliation: Prince of Wales Hospital, Barker St, Randwick, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: A S
authors.initials: AS
authors.lastname: Sim
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.forename: D E L
authors.initials: DE
authors.lastname: Wilcken
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase