Andrew P J, Mayer B
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Cardiovasc Res. 1999 Aug 15;43(3):521-31. doi: 10.1016/s0008-6363(99)00115-7.
Nitric oxide (NO) is synthesised from L-arginine by the enzyme NO synthase (NOS). The complex reaction involves the transfer of electrons from NADPH, via the flavins FAD and FMN in the carboxy-terminal reductase domain, to the haem in the amino-terminal oxygenase domain, where the substrate L-arginine is oxidised to L-citrulline and NO. The haem is essential for dimerisation as well as NO production. The pteridine tetrahydrobiopterin (BH4) is a key feature of NOS, affecting dimerisation and electron transfer, although its full role in catalysis remains to be determined. NOS can also catalyse superoxide anion production, depending on substrate and cofactor availability. There are three main isoforms of the enzyme, named neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS), which differ in their dependence on Ca2+, as well as in their expression and activities. These unique features give rise to the distinct subcellular localisations and mechanistic features which are responsible for the physiological and pathophysiological roles of each isoform.
一氧化氮（NO）由一氧化氮合酶（NOS）催化L-精氨酸合成。这一复杂反应涉及电子从烟酰胺腺嘌呤二核苷酸磷酸（NADPH）经羧基末端还原酶结构域中的黄素腺嘌呤二核苷酸（FAD）和黄素单核苷酸（FMN）转移至氨基末端加氧酶结构域中的血红素，在此底物L-精氨酸被氧化为L-瓜氨酸和NO。血红素对于二聚化以及NO生成至关重要。蝶啶四氢生物蝶呤（BH4）是NOS的关键特征，影响二聚化和电子转移，尽管其在催化中的完整作用仍有待确定。根据底物和辅因子的可利用性，NOS还可催化超氧阴离子的产生。该酶有三种主要同工型，分别称为神经元型NOS（nNOS）、诱导型NOS（iNOS）和内皮型NOS（eNOS），它们在对Ca2+的依赖性以及表达和活性方面存在差异。这些独特特征导致了不同的亚细胞定位和机制特点，这些特点决定了每种同工型的生理和病理生理作用。
