Nitrosative stress: Metabolic pathway involving the flavohemoglobin
Nitrosative stress: Metabolic pathway involving the flavohemoglobin
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DOI：
10.1073/pnas.95.24.14100
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Stamler, JS
中科院分区：
文献类型：
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作者：
Hausladen, A;Gow, AJ;Stamler, JS
一氧化氮（NO）生物学关注的是将l -精氨酸转化为具有信号和防御功能的分子家族的严格调控的酶促机制。然而，人们对代谢这些分子或关闭信号的途径知之甚少。这种模式在细菌中得到了很好的例证，其中s -亚硝基硫醇(SNO)-一种被鉴定为具有NO合成酶抗菌活性的化合物-引发了通过未知机制介导细菌耐药性的反应。本研究表明，大肠杆菌具有SNO代谢的组成和诱导因子。组成酶(s)将SNO裂解为NO，而细菌血红蛋白是一种广泛分布的黄血红蛋白，其功能尚不清楚，是诱导反应的核心。值得注意的是，该蛋白已经进化出一种新的血红素解毒机制。具体来说，血红素具有双加氧酶的功能，主要产生硝酸盐。因此，这些研究为SNO和NO代谢提供了新的见解，并确定了那些被认为只能通过化学手段发生反应的酶。我们的研究结果还强调，SNO和NO与血红蛋白的反应是进化保守的，但已经适应了细胞特异性功能。
Nitric oxide (NO) biology has focused on the tightly regulated enzymatic mechanism that transforms L-arginine into a family of molecules, which serve both signaling and defense functions. However, very little is known of the pathways that metabolize these molecules or turn off the signals. The paradigm is well exemplified in bacteria where S-nitrosothiols (SNO)-compounds identified with antimicrobial activities of NO synthase-elicit responses that mediate bacterial resistance by unknown mechanisms. Here we show that Escherichia coli possess both constitutive and inducible elements for SNO metabolism. Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed flavohemoglobin of poorly understood function, is central to the inducible response. Remarkably, the protein has evolved a novel heme-detoxification mechanism for NO. Specifically, the heme serves a dioxygenase function that produces mainly nitrate. These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reactions that were thought to occur only by chemical means. Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolutionary conserved, but have been adapted for cell-specific function.