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Copper Isotope Compositions of Superoxide Dismutase and Metallothionein from Post-Mortem Human Frontal Cortex

1
Department of Genetics, Melbourne Brain Centre, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville 3010, Australia
2
Department of Earth Sciences, University of Oxford, South Parks Road, Oxford OX1 3AN, UK
3
Department of Anatomical Pathology, Alfred Hospital, Prahran 3004, Australia
4
The Earth Institute, Columbia University, 104 Hogan Hall, 2910 Broadway, New York, NY 10025, USA
5
The Florey Institute, University of Melbourne, Parkville 3010, Australia
6
Cooperative Research Centre for Mental Health, Parkville 3010, Australia
*
Authors to whom correspondence should be addressed.
Inorganics 2019, 7(7), 86; https://doi.org/10.3390/inorganics7070086
Received: 4 May 2019 / Revised: 24 June 2019 / Accepted: 3 July 2019 / Published: 7 July 2019
(This article belongs to the Special Issue Metals in Neurodegenerative Diseases)
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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. View Full-Text
Keywords: MCICPMS; Alzheimer’s disease; isotope fractionation; copper; superoxide dismutase; metallothionein MCICPMS; Alzheimer’s disease; isotope fractionation; copper; superoxide dismutase; metallothionein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Larner, F.; McLean, C.A.; Halliday, A.N.; Roberts, B.R. Copper Isotope Compositions of Superoxide Dismutase and Metallothionein from Post-Mortem Human Frontal Cortex. Inorganics 2019, 7, 86.

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