The autoxidation of tetrahydrobiopterin revisited - Proof of superoxide formation from reaction of tetrahydrobiopterin with molecular oxygen
The autoxidation of tetrahydrobiopterin revisited - Proof of superoxide formation from reaction of tetrahydrobiopterin with molecular oxygen
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DOI：
10.1074/jbc.m211779200
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发表时间：
2003-07-04
影响因子：
4.8
通讯作者：
de Groot, H
中科院分区：
文献类型：
--
作者：
Kirsch, M;Korth, HG;de Groot, H
人们早就知道，四氢生物蝶呤（H4B）在分子氧的存在下容易自氧化。有证据表明，在这个过程中可能会释放超氧自由基，尽管它们的中间作用从未被直接证明。在本研究中，重新研究了H4B的自氧化，目的是寻找超氧化物形成的直接证据。通过lucigenin的发光激发和DEPMPO-OOH自由基加合物的esr -光谱检测两种特定的实验，明确地证明了游离超氧化物自由基的释放。与一氧化氮的相互作用进一步证实了超氧自由基的产生。建立了自氧化过程动力学。我们的数据完全证实了之前的结论，即H4B与氧的直接反应是由此形成的超氧化物与H4B进一步快速反应的起始反应，从而很可能建立一个由中间四氢生物蝶呤自由基还原分子氧的链式反应过程。最后，由于H4B本身可以诱导氧化应激，体内这种蝶呤的过量产生可能是观察到的病理生理途径加速的原因，这在各种疾病中都很明显。
It has been known for quite some time that tetrahydrobiopterin (H4B) is prone to autoxidation in the presence of molecular oxygen. Evidence has been presented that in this process superoxide radicals may be released, although their intermediacy never has been directly proven. In the present study, the autoxidation of H4B was reinvestigated with the aim to find direct evidence for superoxide formation. By means of two specific assays, namely elicitation of luminescence from lucigenin and ESR-spectrometric detection of the DEPMPO-OOH radical adduct, the release of free superoxide radicals was unequivocally demonstrated. The production of superoxide radicals was further corroborated by interaction with nitric oxide. The kinetics of the autoxidation process was established. Our data fully confirm earlier conclusions that the direct reaction between H4B and oxygen serves as an initiation reaction for the further, rapid reaction of the thus formed superoxide with H4B, thereby very likely establishing a chain reaction process involving reduction of molecular oxygen by the intermediary tetrahydrobiopterin radical. Conclusively, because H4B can per se induce oxidative stress, an in vivo overproduction of this pterin, as is evident in various diseases, may be responsible for the observed acceleration of pathophysiological pathways.