a1 School of Medicine, Health Policy & Practice, University of East Anglia, Norwich NR4 7TJ, United Kingdom
a2 Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, United Kingdom
a3 Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, United Kingdom
The essentiality of copper (Cu) in humans is demonstrated by various clinical features associated with deficiency, such as anaemia, hypercholesterolaemia and bone malformations. Despite significant effort over several decades a sensitive and specific Cu status biomarker has yet to be identified. The present article updates a comprehensive review recently published by the authors which assesses the reliability and robustness of current biomarkers and outlines the on-going search for novel indicators of status(1). The essential features of this earlier review are reiterated whilst considering whether there are other approaches, not yet tested, which may provide valuable information in the quest for an appropriate measure of copper status. Current biomarkers include a range of cuproenzymes such as the acute phase protein caeruloplasmin and Cu-Zn-superoxide dismutase all of which are influenced by a range of other dietary and environmental factors. A recent development is the identification of the Cu chaperone, CCS as a potential biomarker; although its reliability has yet to be established. This appears to be the most promising potential biomarker, responding to both Cu deficiency and excess. The potential for identifying a ‘suite’ of biomarkers using high-throughput technologies such as transcriptomics and proteomics is only now being examined. A combination of these technologies in conjunction with a range of innovative metal detection techniques is essential if the search for robust copper biomarkers is to be successful.
Abbreviations: ATOX1, copper chaperone for ATP7A (Menkes protein) and ATP7B (Wilson protein); ATP7A, human copper-transporting P-type adenosine triphosphatase; ATP7B, human copper-transporting P-type adenosine triphosphatase; CCO, cytochrome c oxidase; CCS, copper chaperone for SOD1; CTR1, copper transporter 1; Cox17, copper chaperone for CCO; CU, copper; Fe, iron; SOD1, Cu, Zn superoxide dismutase; ZN, zinc