Abstract
The natural copper isotopic compositions of superoxide dismutase and metallothionein from six post-mortem human frontal cortices were determined using a combination of size exclusion protein liquid chromatography, followed by anion exchange chromatography and multiple collector inductively-coupled plasma mass spectrometry. Superoxide dismutase was enriched in the heavier 65Cu relative to the metallothionein fraction in all specimen pairs. The isotopic compositions were independent of copper content. This finding provides evidence that nitrogen ligands in protein copper binding sites will be enriched in heavy metal isotopes, and sulphur ligands will preferentially incorporate lighter isotopes in vivo. This in turn has implications for understanding isotopic distributions within different components in the body and the dominant ligands in different tissues. Differences in Cu isotope distributions between the two proteins were seen between Alzheimer’s disease and healthy control samples, when normalised for sex.
Highlights
Trace metals are important for many biological functions and have a significant role in health and disease [1]
The aim of this study is to demonstrate a novel combination of HPLC and high precision isotopic analysis for the isolation and subsequent determination of copper isotope compositions in cortex samples, as a new tool to investigate copper metabolic changes in neurodegenerative diseases
The copper isotope composition of superoxide dismutase (SOD) relative to metallothionein was found to be significantly heavier in all specimens analysed as part of this study regardless of disease state and gender, with the exception of the female Alzheimer’s disease specimen (AD3, Table 1) for which no significant difference in isotope composition was found between the two complexes
Summary
Trace metals are important for many biological functions and have a significant role in health and disease [1]. Differences in the isotopic fractionation of copper, zinc and iron have been found in an array of diseases relative to healthy controls [6,7,8,9,10,11], as well as in the ranges of “healthy” values in relation to age, sex and dietary intake [12,13,14,15]. These differences have been found in diverse tissue types including serum, urine
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