Copper

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Copper is a reddish chemical element. It has many uses, mainly due to the fact that it is a good conductor of heat and electricity and is very ductile.¹ Figure 1 is a graphic that displays the many diverse uses of copper.

 

Figure 1 Source

Copper can be found naturally, and can be obtained by electrolysis, smelting and leaching minerals and ores that contain copper.¹ Some places of natural occurrence are:^1,2

• Minerals such as bornite and chalcopyrite
• Sea corals and seaweeds
• Basaltic lavas
• Mollusks and arthropods
• Human liver
• Foods
  • Shellfish
  • Seeds and nuts
  • Wheat bran cereals
  • Organ meats
  • Chocolate
  • Whole-grain products

Copper is an essential element biologically.² It is utilized in many enzymatic and physiological processes.² Some examples are shown below in Table 1.²

Table 1

Enzymatic Processes	Physiologic Processes
Iron metabolism	Neurohormone homeostasis
Neuropeptide activation	Angiogenesis
Energy production	Regulation of immune system functioning, gene expression, pigmentation, brain development
Synthesis of neurotransmitters and connective tissue

 

Biotransformation

It its oxidative states of +1 and +2, copper will form compounds. Copper(I) compounds are considered cuprous compounds, and will combine with oxygen, chlorine and sulfur to form Cu₂O (cuprous oxide), Cu₂Cl₂ (cuprous chloride) and Cu₂S (cuprous sulfide).³ Copper(II) compounds are considered cupric compounds, and will combine with oxygen, chlorine and sulfate to form CuO (cupric oxide), CuCl₂ (cupric chloride), cupric sulfate CuSO₄ (cupric sulfate).³

Toxicokinetics

Pharmacokinetics of copper are as follows:⁴

Absorption: Copper is absorbed in the stomach to the distal small intestine following oral intake

Distribution: Mediated by copper binders, primarily ceruloplasmin and albumin

Metabolism/Excretion: Bile

Figure 2 depicts the pharmacokinetics of copper.

Figure 2 Source

Acute and chronic poisoning occurs mainly from ingestion of copper from contaminated food and water sources. Common side effects are shown in Figure 3, and listed in Table 2.⁵

 

Figure 3 Source

 

Table 2

Acute Toxicities	Chronic Toxicities
GI mucosal ulcerations and bleeding	Hepatic disease
Acute hemolysis and hemoglobinuria	Neurotoxicity
Hepatic necrosis with jaundice	Hemolytic anemia
Nephropathy with azotemia and oliguria
Hypotension
Tachypnea
Dizziness
Headache
Convulsions
Lethargy
Stupor
Coma

Target Organs of Toxicity⁵

Gastrointestinal system

Liver

Kidney

Hematological system

Cardiovascular system

Central nervous system

 

Carcinogenicity

There have been many studies analyzing the relationship of cancer with copper. The conclusions of the studies are compounded by the fact that cancer can result in elevated copper levels. It is concluded that elevated copper levels could be a result of cancer. Studies are inconclusive if elevated copper is a factor for increased carcinogenicity. A great resource summarizing studies of carcinogenicity can be found at this link.⁵

https://www.ncbi.nlm.nih.gov/books/NBK225400/

 

Genetic Susceptibility 

There are three genetic disorders of copper. They are Wilson’s Disease, Menkes Disease and occipital horn syndrome.⁶ Wilson’s Disease is characterized by copper excess, while Menkes Disease and occipital horn syndrome are characterized by copper deficiency.⁶ Below is a nice overview of Wilson’s Disease. I have also provided this link to an article discussing these diseases. The article provides a nice table with information regarding these three diseases.

Treatments

Wilson’s Disease⁶

• Penicillamine
• Trientine
• Zinc

Menkes Disease and Occipital Horn Syndrome⁶

•  Parenteral copper

Biomarkers⁷

Caeruloplasmin

CCS (copper chaperone)

References

1. Royal Society of Chemistry. Copper. Royal Society of Chemistry Periodic Table. Accessed June 15, 2021. https://www.rsc.org/periodic-table/element/29/copper
2. National Institutes of Health. Copper Factsheet for Healthcare Professionals. National Institutes of Health. Updated March 29, 2021. Accessed June 15, 2021. https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/
3. Britannica, The Editors of Encyclopaedia. “Copper”. Encyclopedia Britannica, 28 Oct. 2020, https://www.britannica.com/science/copper. Accessed 28 July 2021.
4. Wapnir, RA. Copper absorption and bioavailability. (1998). The American Journal of Clinical Nutrition. 67(5): 1054S–1060S. https://doi.org/10.1093/ajcn/67.5.1054S
5. National Research Council (US) Committee on Copper in Drinking Water. Copper in Drinking Water. Washington (DC): National Academies Press (US); 2000. 5, Health Effects of Excess Copper. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225400/
6. Kodama, H, Fujisawa, C, Bhadhprasit, W. (2012). Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment. Curr Drug Metab. 13(3): 237–250. doi: 10.2174/138920012799320455
7. Harvey LJ, McArdle HJ. Biomarkers of copper status: a brief update. British Journal of Nutrition. 2008;99(S3):S10-S13. doi:10.1017/S0007114508006806