Intermediates in the Reactions of Pterin-Dependent Hydroxylases

有了这个奖项，化学部的生命过程化学项目资助德克萨斯大学圣安东尼奥健康科学中心的Paul菲茨帕特里克博士研究食物代谢并转化为新细胞和组织时氧被激活的机制。空气中的氧分子由两个氧原子结合在一起组成。 生物体能够将这些原子并入生物分子中，这是一个非自发的过程，需要分子氧的活化。 为了实现这一目标，他们使用含有金属离子的酶。 菲茨帕特里克博士将研究含铁的酶，并致力于阐明氧、含铁的酶和酶底物之间的化学相互作用所形成的中间体。 这项工作对我们理解氧气为生物体提供动力的基本化学以及下一代科学家的培训产生了广泛的影响，其中包括本科生，否则他们可能没有机会参与科学研究。在这个项目中进行的实验的目标是确定以前未知的步骤，在激活氧的非血红素蝶呤依赖性酶。各种光谱方法被用来确定酪氨酸羟化酶与酪氨酸和四氢蝶呤作为模型的四元复合物与氧结合的NO复合物的结构。快速反应方法也被用来捕获和表征色氨酸羟化酶反应中的中间体，并解决质子转移在氧-氧键裂解中的作用。

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.