Wang J, Sim A S, Wang X L, Wilcken D E L
Prince of Wales Hospital, Barker St, Randwick, Sydney, NSW, Australia.
Cell Mol Life Sci. 2006 Dec;63(23):2838-46. doi: 10.1007/s00018-006-6271-8.
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.
循环中不对称二甲基精氨酸（ADMA）水平升高以及L-精氨酸/ADMA比值降低与内皮一氧化氮（NO）生成减少和血管疾病风险增加相关。我们探讨了肝脏（HepG2）细胞中ADMA、L-精氨酸和二甲基精氨酸二甲胺水解酶（DDAH）之间的关系。DDAH是ADMA代谢的主要酶。在无L-精氨酸的情况下，HepG2细胞每3.6×10⁶个细胞每小时代谢44.8 nmol的ADMA。在培养的HepG2细胞中，生理水平（1μmol/L，p<0.01）和病理水平（100μmol/L，p<0.01）的ADMA代谢均受到L-精氨酸（0 - 400μmol/L）的剂量依赖性抑制，并且细胞内ADMA增加（p = 0.039）。L-精氨酸将DDAH酶活性竞争性抑制至未处理水平的5.6±2.0%（p<0.01）。我们得出结论，L-精氨酸通过与DDAH竞争来剂量依赖性地调节ADMA代谢，从而维持L-精氨酸和ADMA的代谢平衡以及内皮NO稳态。
