Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase
Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase
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DOI：
10.1006/niox.2001.0332
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发表时间：
2001-04-01
影响因子：
3.9
通讯作者：
Mayer, B
中科院分区：
文献类型：
--
作者：
Gorren, ACF;Kungl, AJ;Mayer, B
四氢生物蝶呤（BH4）是一氧化氮合酶（NOS）的重要辅助因子，但其功能尚不完全清楚。具体来说，BH4是否直接参与电子转移尚不清楚。利用循环伏安法和奥斯特杨方波伏安法研究了BH4和其他几种翼啶化合物的氧化还原性质。BH4在+0.27 V的电位下与普通氢电极（NHE）氧化；扫描方向反转后对应的约化信号很小。相反，还原发生在-0.16 V vs NHE电位下；没有相应的氧化信号。这两种转变是相互依赖的，表明-0.16 V的还原波代表BH4从+0.27 V的氧化产物中再生。四氢蝶呤和6,7-二甲基四氢蝶呤均可替代BH4进行NOS催化，得到相似的伏安图。7,8-二氢生物蝶呤、七氢蝶呤、2'-脱氧七氢蝶呤和氧化BH4得到了完全不同的伏安图。这些不支持NOS催化的7,8-二氢蝶呤在更高的电位下被氧化（+0.82-1.04 V vs NHE），并且在+1.2和-0.8 V之间没有明显的还原，这符合BH4在NOS催化中的氧化还原作用的概念。然而，有效的pterin-site NOS抑制剂4-氨基-BH4的电化学性质与BH4相似，而活性的pterin辅助因子5-甲基-BH4氧化后没有再还原。我们得出结论，BH4和类醌双氢生物蝶呤之间的蝶呤辅助因子的2电子氧化还原循环对NO合成不是必需的。这些数据与BH4与三氢生物蝶呤自由基BH3之间的1电子氧化还原循环一致（.）。(C) 2001学术出版社。
Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), but its function is not fully understood. Specifically, it is unclear whether BH4 participates directly in electron transfer. We investigated the redox properties of BH4 and several other pteridines with cyclic voltammetry and Osteryoung square wave voltammetry. BH4 was oxidized at a potential of +0.27 V vs normal hydrogen electrode (NHE); the corresponding reductive signal after the reversal of the scan direction was very small. Instead, reduction occurred at a potential of -0.16 V vs NHE; there was no corresponding oxidative signal. These two transitions were interdependent, indicating that the reductive wave at -0.16 V represented the regeneration of BH4 from its product of oxidation at +0.27 V. Similar voltammograms were obtained with tetrahydroneopterin and 6,7-dimethyltetrahydropterin, both of which can substitute for BH4 in NOS catalysis. Completely different voltammograms were obtained with 7,8-dihydrobiopterin, sepiapterin, 2'-deoxysepiapterin, and autoxidized BH4. These 7,8-dihydropterins, which do not sustain NOS catalysis, were oxidized at much higher potentials (+0.82-1.04 V vs NHE), and appreciable reduction did not occur between +1.2 and -0.8 V, in line with the concept of a redox role for BH4 in NOS catalysis. However, the electrochemical properties of the potent pterin-site NOS inhibitor 4-amino-BH4 resembled those of BH4, whereas the active pterin cofactor 5-methyl-BH4 was not re-reduced after oxidation. We conclude that the 2-electron redox cycling of the pterin cofactor between BH4 and quinonoid dihydrobiopterin is not essential for NO synthesis. The data are consistent with 1-electron redox cycling between BH4 and the trihydrobiopterin radical BH3(.). (C) 2001 Academic Press.