Intermediates in the Reactions of Pterin-Dependent Hydroxylases

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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.