Abstract
Dopamine Beta-Hydroxylase is the enzyme responsible for hydroxylating dopamine to generate norepinephrine in the brain. This synthetic pathway of norepinephrine describes the synthetic foundation for the noradrenergic cycle. The cycle is essential for the neurological function of humans and other organisms. Inhibition of this process and the participating enzymes has been found to lead to Parkinson’s disease along with numerous other neurological and physiological failures. The structure of the active site of Dopamine-beta Hydroxylase contains a binuclear copper complex responsible for the hydroxylation of dopamine substrate, but the current mechanistic understanding of this hydroxylation reaction involves a poorly understood and supported fast electron transfer step. This project aims to support this fast electron transfer step within the current mechanism. By individually modeling the two copper centers termed CuM and CuH with mononuclear, functionally similar coordination complexes, the proposed functionality of each copper center in relation to the overall proposed mechanism can be supported or opposed. These copper model complexes were synthesized from commercial starting materials and characterized by nuclear magnetic resonance and visible light absorption spectroscopy. Visible light absorption spectroscopy and electron paramagnetic resonance were utilized to compare the redox activities of these mononuclear complexes to those expected by the individual copper centers in the dopamine beta- hydroxylase enzyme. Data from visible light absorption supported the individual redox functionality of the CuM site model, put only the partial individual functionality of the CuH site model. Electron paramagnetic resonance data to evaluate the dual functionality of the models is pending.
Advisor
Gallo, Annastassia
Department
Chemistry
Recommended Citation
Harvey, Eli J., "Interrogation of the Dopamine Beta-Hydroxylase Mechanism Through Biomimetic Modeling" (2024). Senior Independent Study Theses. Paper 11157.
https://openworks.wooster.edu/independentstudy/11157
Disciplines
Arts and Humanities
Keywords
Copper, Dopamine Beta-Hydroxylase, Mechanism, Biomimetic Modeling
Publication Date
2024
Degree Granted
Bachelor of Arts
Document Type
Senior Independent Study Thesis
Final Submission
© Copyright 2024 Eli J. Harvey