Kinoshita H, Tsutsui M, Milstien S, Katusic Z S
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
Prog Neurobiol. 1997 Jul;52(4):295-302. doi: 10.1016/s0301-0082(97)00017-8.
Tetrahydrobiopterin is an essential cofactor required for activity of nitric oxide synthases. Existing evidence suggests that, during activation of constitutive and inducible isoforms of nitric oxide synthase, tetrahydrobiopterin is needed for allosteric and redox activation of enzymatic activity. However, precise mechanisms underlying the role of tetrahydrobiopterin in regulation of nitric oxide formation is not fully understood. In cerebral and peripheral arteries, increased availability of tetrahydrobiopterin can augment production of nitric oxide. In contrast, in arteries depleted of tetrahydrobiopterin, production of nitric oxide is impaired. Proinflammatory cytokines enhance mRNA expression of the rate-limiting enzyme of tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I and stimulate production of tetrahydrobiopterin. The ability of vascular tissues to synthesize tetrahydrobiopterin plays an important role in regulation of nitric oxide synthase under physiological conditions as well as during inflammation and sepsis. More recent studies concerning expression and function of recombinant nitric oxide synthases suggest that availability of tetrahydrobiopterin is important for production of nitric oxide in genetically engineered blood vessels. In this review, mechanisms regulating availability of intracellular tetrahydrobiopterin and its role in control of vascular tone under physiological and pathological conditions will be discussed.
四氢生物蝶呤是一氧化氮合酶活性所必需的辅助因子。现有证据表明，在组成型和诱导型一氧化氮合酶激活过程中，四氢生物蝶呤对于酶活性的变构激活和氧化还原激活都是必需的。然而，四氢生物蝶呤在调节一氧化氮生成中所起作用的精确机制尚未完全明确。在脑动脉和外周动脉中，四氢生物蝶呤可用性增加可增强一氧化氮的生成。相反，在四氢生物蝶呤缺乏的动脉中，一氧化氮的生成受损。促炎细胞因子可增强四氢生物蝶呤生物合成限速酶鸟苷三磷酸环化水解酶I的mRNA表达，并刺激四氢生物蝶呤的生成。血管组织合成四氢生物蝶呤的能力在生理条件下以及炎症和脓毒症期间对一氧化氮合酶的调节中起着重要作用。关于重组一氧化氮合酶表达和功能的最新研究表明，四氢生物蝶呤的可用性对于基因工程血管中一氧化氮的生成很重要。在这篇综述中，将讨论调节细胞内四氢生物蝶呤可用性的机制及其在生理和病理条件下对血管张力控制中的作用。
