Abstract
Observations that copper and homocysteine levels are simultaneously elevated in patients with cardiovascular disease has generated interest in investigating the interactions between copper and homocysteine. Several prior studies have shown that complexes of copper and homocysteine are toxic, leading to cardiovascular damage in vitro. It is not clear, however, why related effects do not occur with other structurally similar, more abundant cellular thiols such as glutathione and cysteine. Herein, a mechanism for a selective redox interaction between copper and homocysteine is demonstrated. It involves a kinetically favored intramolecular hydrogen atom transfer that results in an alpha-amino carbon-centered radical known to promote biomolecular damage.
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The authors thank Portland State University for its support of this work. The National Science Foundation is acknowledged for support of the BioAnalytical Mass Spectrometry Facility at PSU (MRI 1828573).
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MG performed experiments, acquired analytical and chromatographic data, interpreted results and wrote the manuscript. JMA interpreted results, assisted with experiments and proofread the manuscript. RMS conceived of the study, guided the work and contributed to manuscript preparation.
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Gupta, M., Meehan-Atrash, J. & Strongin, R.M. Identifying a role for the interaction of homocysteine and copper in promoting cardiovascular-related damage. Amino Acids 53, 739–744 (2021). https://doi.org/10.1007/s00726-021-02979-9
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DOI: https://doi.org/10.1007/s00726-021-02979-9