四氢生物蝶呤代谢紊乱导致一氧化氮合酶解耦联的分子机制  

The Molecular Mechanism of Nitric Oxide Synthase Uncoupling Induced by the Tetrahydrobiopterin Metabolic Disorders

作　　者：焦亮[1] 邓乃刚[2] 门秀丽[2] 李治国[3] 

机构地区：[1]河北联合大学研究生院,河北唐山063000 [2]河北联合大学病理生理学系教研室,河北唐山063000 [3]河北联合大学医学实验研究中心,河北唐山063000

出　　处：《医学综述》2013年第12期2119-2121,共3页Medical Recapitulate

基　　金：国家自然科学基金(81100518)

摘　　要：一氧化氮合酶(NOS)合成的一氧化氮(NO)是调节血管舒张功能的重要因子。四氢生物蝶呤(BH4)是NOS的重要辅助因子。BH4在体内的稳定性由从头合成、补救合成、氧化消耗及再循环所决定。当BH4/NOS的比例失调,可导致NOS催化L-精氨酸的作用解耦联,NOS催化产物由NO变为超氧阴离子(O2-)。O2-能与NO反应生成氧化性很强的氧亚硝基(ONOO-),ONOO-能迅速氧化BH4,加剧NOS的解耦联。NOS解耦联是高血压病、糖尿病、动脉粥样硬化等疾病中内皮细胞功能障碍的重要原因,因而通过纠正NOS解耦联可有效改善内皮细胞功能,有望为保护血管内皮功能提供有效途径。Nitric oxide（ NO）, a key regulator of cardiovascular tunction,is synthesized trom L-arglmne and oxygen by the enzyme nitric oxide synthase（NOS）. This reaction requires tetrahydrobiopterin（ BH4 ） as a cofactor. The stability of BH4 in the human body is determined by de novo synthesis, remedial synthesis, oxidative consumption and recycling. When BH4/NOS is imbalanced, NOS is ＂ uncoupled＂ from L-arginine oxidation,and NOS produces superoxide （O2^- ）instead of NO. NOS-derived superoxide reacts with NO to produce peroxynitrite （ ONOO^- ）, a highly reactive anion which can rapidly oxidize BH4, accelerating the upcoupling of BH4. BH4 depletion and NOS uncoupling contributes to endothelial dysfunction in hyperten-sion, diabetes, artery atherosclerosis and other diseases. Fixation the uncoupling of NOS can effectively improve endothelial function,which is hopefully to be an effective way to protect vascular endothelial function.

关 键 词：四氢生物蝶呤 一氧化氮 一氧化氮合酶解耦联 超氧阴离子 

分 类 号：R914[医药卫生—药物化学]