INVESTIGATIONS OF THE BIOCHEMISTRY OF VANADIUM

钒的生物化学研究

• 批准号: 3466143
• 负责人: Alison Butler
• 金额: $ 5.13万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3466143
• 关键词: biochemistry; bleomycin; carbonate dehydratase; carboxypeptidase; catalase; catalyst; cytosine; deferoxamine; electron transport; hydrogen peroxide; lactoferrin; macromolecule; metalloproteins; oxidation reduction reaction; peroxidases; superoxide dismutase; thermolysin; transferrin; uracil; vanadium

The goal of this work is to improve our understanding of the biological function of vanadium, in general, and to investigate the reactivity of vanadium-containing proteins, more specifically. Vanadium is capable of existing in many oxidation states and the aqueous chemistry of vanadium is dominated by electron transfer, hydrolysis and/or polymerization reactions. Clearly the coordination environment of the vanadium will affect its reactivity. Towards our overall goal, we proposed to investigate the factors that govern the oxidation and reduction reactions of vanadium bound to macromolecules (eg., the naturally occurring V-bromoperoxidase and V substituted derivatives of transferrin, lactoferrin, ovotransferrin, carboxypeptidase A, carbonic anhydrase B, thermolysin, bleomycin, etc), and to examine the possibility that vanadium proteins catalyze the disproportionation of superoxide (i.e., superoxide dismutase activity), participate in the disproportionation of hydrogen peroxide (i.e., catalase activity) and/or halogenate certain organic substrates in the presence of H2O2 (i.e., haloperoxidase activity). We have found that several V(V) complexes catalyze the decomposition of hydrogen peroxide, including V2-transferrin, V(V)-(8- hydroxyuinoline)(O)(OCH3) and V(V)-desferoxamine. The later two are catalyzed by ultraviolet light. We also propose to further characterize the vanadium bromoperoxidase (V-BrPO) isolated from Ascophyllum nodosum and Laminaria setchellii. We have discovered that this enzyme brominates the pyrimidine-containing nucleic acid bases, cytosine and uracil. Experiments are proposed to probe the substrate specificity by variation of the pyrimidine-ring substituents. Experiments are also proposed to probe the function of the vanadium. Does the vanadium act as a Lewis acid catalyst or an electron transfer catalyst, cycling between oxidation states? These mechanistic studies will be further probed using the model complex, V(V)-desferoxamine, which we have shown catalyzes the same bromination reactions as the V-BrPO.

这项工作的目的是提高我们对 通常，钒的生物学功能，并研究 更具体地说，含钒蛋白的反应性。 钒能够存在于许多氧化状态和 钒的水性化学因电子转移的主导， 水解和/或聚合反应。 显然 钒的协调环境将影响其 反应性。 达到我们的整体目标，我们建议调查 控制氧化和还原反应的因素 钒结合到大分子（例如，天然发生的 V-溴过氧化物酶和V取代的转铁蛋白衍生物， 乳铁蛋白，卵纤维蛋白，羧肽酶A，碳纤维肽 赤道酶B，热霉素，博来霉素等），并检查 钒蛋白会催化不成比例的可能性 超氧化物（即超氧化物歧化酶活性）参与 过氧化氢的比例（即过氧化氢酶 活性）和/或卤化某些有机底物 H2O2的存在（即卤代氧化酶活性）。 我们找到了 几个V（V）复合物催化了 过氧化氢，包括V2-转铁蛋白，V（V） - （8- 羟基二酚）（O）（OCH3）和V（V） - 脱氧胺。 后来 两个被紫外线催化。 我们还建议进一步描述钒 从腹膜结膜中分离的溴过氧化物酶（V-BRPO） 和Laminaria setchellii。 我们发现这种酶 溴化含嘧啶的核酸碱基，胞嘧啶 和乌拉西尔。 提出了实验以探测基材 嘧啶环取代基的变化特异性。 还提出了实验来探测 钒。 钒是刘易斯酸催化剂还是 电子转移催化剂，氧化态之间的循环？ 这些机械研究将使用模型进一步探讨 复合物v（v） - 脱氧胺，我们已经显示出催化 与V-BRPO相同的溴化反应。