Sponsor
Portland State University. Department of Chemistry
First Advisor
Robert M. Strongin
Term of Graduation
Winter 2025
Date of Publication
3-3-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.) in Chemistry
Department
Chemistry
Language
English
Subjects
albumin, biomolecular mechanisms, copper, dehydroascorbic acid, homocysteine, redox chemistry
Physical Description
1 online resource (xiii, 87 pages)
Abstract
Homocysteine at elevated levels is a well-known independent risk factor for cardiovascular disease. However, it is still unclear, after large scale clinical trials, involving tens of thousands of patients, whether homocysteine is a disease mediator or marker. The disconnect between the basic science showing the association of homocysteine with cardiovascular disease and the outcomes of clinical trials based on vitamin therapy for homocysteine lowering, highlights the need for insights into the molecular mechanisms linking homocysteine to cardiovascular disease and other pathologies. For example, elevated homocysteine levels have also been associated with risk for stroke, venous thromboembolism, Alzheimer's disease, neural tube defects, complications during pregnancy, inflammatory bowel disease and osteoporosis, as well as several additional major disorders.
This project's overall objective is to determine the relationship between homocysteine redox chemistry and molecular mechanisms related to disease. The overall hypothesis of this project is that homocysteine redox chemistry involves an intramolecular hydrogen atom transfer, which is promoted by free and bound copper as well as dehydroascorbic acid.
In keeping with the hypothesis, we herein have provided evidence for the homocysteine redox interaction with biological oxidants to occur via the kinetically favored formation of the strongly reducing and relatively toxic alpha carbon-radical of homocysteine. Additionally, we have shown this hydrogen atom transfer mechanism to occur in homocysteine-containing peptides promoted by protein bound-copper in human serum albumin under physiologically relevant concentrations and conditions.
Rights
© 2025 Megha Gupta
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Persistent Identifier
https://archives.pdx.edu/ds/psu/43149
Recommended Citation
Gupta, Megha, "The Role of Homocysteine Redox Chemistry in Biomolecular Mechanisms" (2025). Dissertations and Theses. Paper 6774.
