Regulation of biosynthesis of nitric oxide.
Regulation of biosynthesis of nitric oxide.
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DOI：
10.1016/s0021-9258(17)36703-0
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发表时间：
1994-05
期刊：
影响因子：
--
通讯作者：
C. Nathan;Q. Xie
中科院分区：
文献类型：
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作者：
C. Nathan;Q. Xie
一氧化氮合酶（NOS）（L-精氨酸，NADPH：氧氧化还原酶（一氧化氮形成）; EC 1.14。13.39）在真核酶中是独特的，是二聚体的、钙调蛋白依赖性的或含钙调蛋白的细胞色素P450样血红素蛋白，其在一个单体中结合联合收割机还原酶和加氧酶催化结构域，携带FAD和FMN，并在四氢生物蝶呤（1）的帮助下进行非芳香族氨基酸（L-精氨酸）的5电子氧化。真核生物在遗传学上古老而多样，如美洲鲎（Limulus polyphemus，2）和长吻红鱼（Rhodnius prolixus，3）都能产生NO，而果蝇和人类等远亲物种也产生了NOS cDNA。一氧化氮（NO）的生物合成似乎在大多数哺乳动物细胞类型（II）的全部功能中，只要它们被适当地刺激。在过去的6年中，已知NO介导巨噬细胞的细胞毒性，调节血压，并参与神经传递（11，12），然而，源源不断的报道继续扩大NO的作用范围。例如，内源性NO可导致宿主关节（13，14）和肾脏（14）的破坏或其从病毒感染中存活（15）。因此，NO生物合成的调控吸引了深入的研究，是本文的主题。其他最近的调查涉及NOS的酶学（1，16）及其生理作用（11，12）。
Nitric oxide synthases (NOSs)'(L-arginine, NADPH: oxygen oxidoreductases (nitric oxide forming); EC 1.14. 13.39) are unique among eukaryotic enzymes in being dimeric, calmodulin-dependent or calmodulin-containing cytochrome P450-like hemoproteins that combine reductase and oxygenase catalytic domains in one monomer, bear both FAD and FMN, and carry out a 5-electron oxidation of a non-aromatic amino acid (L-arginine) with the aid of tetrahydrobiopterin (1). Eukaryotes as phylogenetically ancient and diverse as Limulus polyphemus (2) and Rhodnius prolixus (3) make NO, and species as distantly related as Drosophila'and man (&lo) have yielded NOS cDNAs. Biosynthesis of nitric oxide (NO) appears to be within the repertoire of most mammalian cell types (ll), provided they are appropriately stimulated. NO has been known for the past 6 years to mediate aspects of macrophage cytotoxicity, regulate blood pressure, and participate in neurotransmission (11, 12), yet a steady stream of reports continues to enlarge NO'S sphere of action. For example, endogenous NO can contribute to destruction of the host's joints (13, 14) and kidneys (14) or to its survival from viral infection (15). Accordingly, regulation of NO biosynthesis has attracted intensive study and is the subject of this review. Other recent surveys deal with the enzymology of NOSs (1, 16) and their physiologic roles (11, 12).