Oxidative fragmentation of hydroxy octadecadienoates generates biologically active gamma-hydroxyalkenals.
Oxidative fragmentation of hydroxy octadecadienoates generates biologically active gamma-hydroxyalkenals.
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羟基十八碳二烯酸酯的氧化断裂产生具有生物活性的γ-羟基烯醛。
DOI：
10.1021/ja038756w
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Salomon,RobertG
中科院分区：
文献类型：
--
作者：
Sun,Mingjiang;Salomon,RobertG
体内多不饱和脂肪酸（PUFA）的氧化断裂产生细胞毒性醛。其中，4-羟基壬-2-烯醛和类似的γ-羟基烯醛磷脂酰胆碱（PC）引起了人们的注意，因为这些氧化截短的脂质具有生物活性，并与疾病有关。先前的研究表明，由亚油酸的烯丙位氧化产生的羟基二烯对氧化断裂不起反应。我们现在表明，在氢过氧化物存在下，羟基二烯与相应的氢过氧二烯一样容易断裂，生成γ-羟基烯醛。在一项拟生理模型研究中，髓过氧化物酶促进的自由基诱导的2-溶血-PC的氢过氧-或羟基辛碳二烯酸酯在小单层囊泡中的片段化产生了9-羟基-12-氧代十二碳-10-烯酸（HODA）酯HODA-PC。因此，羟基二烯，通常是更丰富的体内比过氧化氢二烯，是合理的中间体在体内的氧化截短的脂质的生产中，自由基和氢过氧化物的恒定流量是存在的。我们的研究结果还表明，通过过氧自由基环化形成的二氧杂环丁烷中间体是不需要实现氧化裂解的PUFA。
Oxidative fragmentation of polyunsaturated fatty acids (PUFAs) in vivo generates cytotoxic aldehydes. Among these, 4-hydroxynon-2-enal and analogous γ-hydroxyalkenal phosphatidylcholines (PCs) have attracted attention because these oxidatively truncated lipids are biologically active and have been implicated in diseases. A previous study showed that hydroxydienes, generated by allylic oxygenation of linoleic acid, are unreactive toward oxidative fragmentation. We now show that, in the presence of hydroperoxides, hydroxydienes fragment as readily as the corresponding hydroperoxydienes, generating γ-hydroxyalkenals. In a physiomimetic model study, myeloperoxidase-promoted free radical-induced fragmentation of either hydroperoxy- or hydroxyoctecadienoate esters of 2-lyso-PC in small unilamellar vesicles produced the 9-hydroxy-12-oxododec-10-enoic acid (HODA) ester HODA-PC. Therefore, hydroxydienes, that are generally more abundant in vivo than hydroperoxydienes, are plausible intermediates in the production of oxidatively truncated lipids in vivo where a constant flux of radicals and hydroperoxides is present. Our findings also show that the formation of dioxetane intermediates through peroxyradical cyclization is not required to achieve oxidative fragmentation of PUFAs.