Last revised by Daniel J Bell on 27 Sep 2021

Copper (chemical symbol Cu) is one of the trace elements. It has an important biological role as a redox agent and as a cofactor in cuproproteins, facilitating many vital metabolic reactions.

Copper is a transition metal with the atomic number 29 and an atomic weight of 63.54. It has three main valency states: Cu2+ is stable in vivo, whilst Cu+ and Cu3+ tend to be unstable. 

There are two natural stable isotopes of copper, copper-63 and copper-65, the former accounting for almost 70% of the copper on earth. In addition 27 unstable isotopes are known, but the ones that have shown most promise for labeling radiotracers in nuclear medicine are copper-60, -61, -62, -67, and particularly Cu-64 5,7.

In general, nuts, internal animal organs (i.e. offal), and - in lesser quantities - grains and fruit are the best dietary sources for copper. Dairy products tend to be lacking 2. Local environmental conditions tend to affect the copper content of foods, due to different soil concentrations of copper, copper in air pollution, cupric compounds in fertilisers, etc.

Copper is absorbed primarily in the duodenum, and much smaller quantities in the stomach and distal ileum. The human copper transport protein 1 (hCTR1) facilitates most enteric uptake, although the divalent metal transporter 1 protein also contributes 3

In the circulation copper is complexed to several carrier proteins, including albumin, transcuprein, and histidines. The bloodstream transports the copper to the liver, where hCTR1 facilitates absorption into the hepatocytes 3

Intracellular cytoplasmic copper has three main fates:

  1. complexes with metallothionein proteins for storage
  2. joins to a 'copper chaperone' for transfer to a specific protein
  3. links to reduced glutathione

Overall body stores of copper are small, at maximum 100 mg, mostly in the liver, but also brain, kidney, and heart.

It exists in two main oxidation states: oxidised (Cu2+) and reduced (Cu+), which underpin its main biological function aiding redox reactions by releasing and accepting electrons. 

Copper is essential for the functioning of many cuproproteins, which are a form of metalloprotein, consisting of a protein complexed with one or more copper atoms.

Cuproproteins include:

  • ceruloplasmin: important carrier protein for copper
  • cytochrome c oxidase
  • tyrosinase

Copper is also a hematinic.

Copper deficiency is rare due to the good dietary availability of copper. One of the main congenital causes is Menkes disease 3. Its main manifestations are various blood dyscrasias and neurological dysfunction (see main article). Its effects are very similar to those of vitamin B12 deficiency.

Copper toxicity is unusual and is most commonly seen as part of Wilson disease. Idiopathic copper toxicosis (ICT), a pediatric condition is a rare cause, and its existence as a true separate disease entity is contentious; some believe it to result from subclinical Wilson disease which is then exacerbated by reduced dietary copper intakes 3. Chronic copper excess characteristically results in hepato- and/or neurotoxicity.

Copper-containing fumes have also been implicated as a precipitant in metal fume fever, although this is contentious 6.

  • various copper isotopes have been trialled for use as labels for PET radiotracers 4,5,7:
    • copper-62 PTSM has been employed to measure myocardial perfusion
  • copper-65 is used as a radiotracer in clinical chemistry to evaluate the metabolism of copper 7
  • copper has been used since prehistoric times, its name derives ultimately from the Latin for Cyprus, as the element was found there

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