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UBC Theses and Dissertations

Metal ion distribution in blood plasma : towards metallo-proteomics Levesque, Chantal A.


Considering the immense involvement of metal ions in metabolism, protein structure, electron transfer, and their relation to health and disease, deciphering the mechanisms by which metals are stored, transported, sensed and incorporated within the human biosystem is imperative to further understand metal homeostasis and metal-related diseases. In this "omics" age, the emerging field of metallomics sets out to do just that. The metallome of a tissue, fluid, or cell includes aquated trace elements and their complexes with endogenous and induced biomolecules, including organic acids, sugars, proteins, and oligonucleotides. Metallomic studies seek to determine the distribution of elements in a sample, the coordination environments of that element, and the concentrations of each metalcontaining species present. The technology involved combines protemics methods with elemental analysis techniques. The most promising approach to studying the blood plasma metallome involves coupling size-exclusion chromatography (SEC) to inductively coupled plasma mass spectrometry (ICP-MS). This platform technology produces a two-dimensional metal distribution plot of the plasma proteome. The first phase separates the plasma's components based on size, and the resulting fractions are analyzed for metal content in the second phase. Combining two well-characterized and widely used analytical techniques, SEC and ICP-MS, effectively maps out where and how the transition elements distribute themselves in plasma. However, while few plasma metallomic studies have been reported to date, the involvement of the protein separation step (SEC) and its impact on the sample integrity prior to metal analysis has not been investigated, bringing into question the potential for processing artifacts.

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