Mayer B, Andrew P
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jul;358(1):127-33. doi: 10.1007/pl00005233.
Biosynthesis of nitric oxide (NO) is performed by the dimeric, heme-containing enzyme nitric oxide synthase, which requires the flavins FAD and FMN, as well as the pteridine cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin) in order to catalyze the NADPH-dependent oxidation of L-arginine. The three major isoforms of nitric oxide synthase (NOS), although identical in that they contain a carboxy-terminal reductase and an amino-terminal oxygenase domain, fulfill diverse physiological functions, according to their differing expression patterns and mechanisms of activation. The pteridine H4biopterin, which affects both the conformational stability and activity of NOS, demonstrates anticooperative binding which results in the stoichiometric production of NO and O2-. Physiological mechanisms involving superoxide dismutase and reduced glutathione exist to avoid the subsequent formation of the potent oxidant peroxynitrite. With regard to inhibition of NO production, novel isoform-selective inhibitors are proving useful not only for dissecting the physiological functions of NOS, but also in the development of novel therapeutic agents.
一氧化氮（NO）的生物合成由含血红素的二聚体酶一氧化氮合酶完成，该酶需要黄素FAD和FMN以及蝶啶辅因子（6R）-5,6,7,8-四氢-L-生物蝶呤（H4生物蝶呤）来催化L-精氨酸的NADPH依赖性氧化。一氧化氮合酶（NOS）的三种主要同工型虽然都含有羧基末端还原酶和氨基末端加氧酶结构域，但根据其不同的表达模式和激活机制，发挥着不同的生理功能。蝶啶H4生物蝶呤影响NOS的构象稳定性和活性，表现出反协同结合，导致化学计量地产生NO和O2-。存在涉及超氧化物歧化酶和还原型谷胱甘肽的生理机制以避免随后形成强氧化剂过氧亚硝酸盐。关于抑制NO的产生，新型同工型选择性抑制剂不仅被证明有助于剖析NOS的生理功能，而且在新型治疗药物的开发中也很有用。
