Intermediates in the Reactions of Pterin-Dependent Hydroxylases

该奖项将资助德克萨斯大学圣安东尼奥分校健康科学中心的Paul Fitzpatrick博士研究食物代谢并转化为新细胞和组织时氧气被激活的机制。空气中的分子氧由两个结合在一起的氧原子组成。活着的生物体能够将这些原子结合到生物分子中，这一过程不是自发的，需要分子氧的激活。为了实现这一目标，他们使用了含有金属离子的酶。Fitzpatrick博士将研究一种含铁酶，并致力于阐明氧、含铁酶和酶底物之间的化学作用所形成的中间产物。这项工作对我们对氧气为生物体提供动力的基础化学的理解，以及对下一代科学家的培训产生了广泛的影响，其中包括可能没有机会参与科学研究的本科生。这个项目中正在进行的实验的目标是确定非血红素蝶呤依赖的酶激活氧气的以前未被表征的步骤。各种光谱方法被用来确定酪氨酸羟基酶与酪氨酸和四氢蝶呤结合的NO络合物的结构，作为该四元络合物与氧的模型。快速反应方法也被用来捕捉和表征色氨酸羟基酶反应中的中间体，并解决质子转移在氧-氧键断裂中的作用。

With this award the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Paul Fitzpatrick of the University of Texas Health Science Center-San Antonio to study the mechanism by which oxygen is activated when food is metabolized and converted into new cells and tissues. Molecular oxygen from the air consists of two oxygen atoms bonded together. Living organisms are capable of the incorporation of these atoms in biomolecules, a process that is not spontaneous and that requires the activation of the molecular oxygen. To achieve this goal, they use enzymes that contain metal ions. Dr. Fitzpatrick will study an iron-containing enzyme and pursue the elucidation of intermediates formed upon the chemical interaction between oxygen, the iron-containing enzyme, and the enzyme substrates. The work is having a broad impact on our understanding of the basic chemistry by which oxygen powers living organisms, as well as on the training of the next generation of scientists, including undergraduates who might not otherwise have the opportunity to become involved in scientific research. The goal of the experiments being carried out in this project is to determine previously uncharacterized steps in the activation of oxygen by non-heme pterin-dependent enzymes. A variety of spectroscopic methods are being used to determine the structure of the NO complex of tyrosine hydroxylase with tyrosine and a tetrahydropterin bound as a model for the quaternary complex with oxygen. Rapid-reaction methods are also being used to trap and characterize an intermediate in the reaction of tryptophan hydroxylase and to address the role of proton transfer in cleavage of the oxygen-oxygen bond.