Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
J Inorg Biochem. 2013 Jan;118:148-54. doi: 10.1016/j.jinorgbio.2012.09.024. Epub 2012 Oct 5.
Recent research has shown that nitroxyl (HNO) has important and unique biological activity, especially as a potential alternative to current treatments of cardiac failure. HNO is a reactive molecule that undergoes efficient dimerization and subsequent dehydration to form nitrous oxide (N(2)O), making its detection in solution or biologically relevant preparations difficult. Due to this limitation, HNO has not yet been observed in vivo, though several pathways for its endogenous generation have been postulated. Here, we investigate the oxidation of N-hydroxy-l-arginine (NOHA) by hypochlorous acid (HOCl), which is generated in vivo from hydrogen peroxide and chloride by the heme enzyme, myeloperoxidase. NOHA is an intermediate in the enzymatic production of nitric oxide (NO) by NO synthases, and has been shown previously to be chemically oxidized to either HNO or NO, depending on the oxidant employed. Using membrane inlet mass spectrometry and standard N(2)O analysis by gas chromatography, we find that NOHA is oxidized by excess HOCl to form HNO-derived N(2)O. In addition, we also observe the analogous production of HNO from the HOCl oxidation of hydroxylamine, hydroxyurea, and (to a lesser extent) acetohydroxamic acid.
最近的研究表明，亚硝酰（HNO）具有重要且独特的生物学活性，特别是作为当前心力衰竭治疗的潜在替代方法。HNO 是一种反应性分子，它会发生有效的二聚化，随后脱水形成一氧化二氮（N2O），这使得其在溶液或生物相关制剂中的检测变得困难。由于这个限制，尽管已经提出了几种内源性生成 HNO 的途径，但它尚未在体内观察到。在这里，我们研究了次氯酸（HOCl）对 N-羟基-L-精氨酸（NOHA）的氧化作用，HOCl 是由血红素酶髓过氧化物酶从过氧化氢和氯离子体内生成的。NOHA 是一氧化氮合酶（NOS）酶促生成一氧化氮（NO）的中间产物，先前已经证明，根据所使用的氧化剂，NOHA 可被化学氧化为 HNO 或 NO。使用膜入口质谱和通过气相色谱进行的标准 N2O 分析，我们发现过量的 HOCl 将 NOHA 氧化形成 HNO 衍生的 N2O。此外，我们还观察到类似的 HOCl 氧化羟胺、羟基脲和（在较小程度上）乙酰羟肟酸生成 HNO。
