Copper

Copper exists in two states within the human body: cuprous (Cu¹⁺) and cupric (Cu²⁺). There are 50-120 milligrams of copper found within the body with the highest concentration within the liver.¹ Copper serves as a cofactor for many bodily reactions and deficiency of copper can cause similar symptoms to iron deficiency anemia.¹

Absorption: Copper is absorbed primarily in the small intestine but also within the stomach.¹ Copper in the cupric form must be reduced into its cuprous form to enter the enterocytes; a group of reductases called Steap proteins along the brush border converts it.¹ Once converted, copper binds to protein carriers to bring into enterocytes. Ctr1 is a transport protein that binds to copper; other carriers include DMT1 and amino acid transporters.¹ Within enterocytes, copper binds to chaperone proteins in the following ways:

• Atox1 transports copper to ATP7A to enter portal blood.¹

• CCS transports copper into super-oxide dismutase (SOD) to form an antioxidant enzyme called copper-zinc superoxide dismutase.¹

• Cox17 transports copper to Cox11 and  Sco1 or Sco2 into cytochrome c oxidase used within the electron transport chain.¹

Excess copper binds to protein metallothionein and is excreted through feces when enterocytes are sloughed off.¹ 

Copper absorption is affected and influenced by other minerals. Excess zinc decreases copper absorption.¹ Zinc impacts copper absorption by increasing the production of protein metallothionein; metallothionein binds and traps zinc but has a greater affinity for copper. Therefore, copper is also lost and excreted as feces when higher metallothionein production occurs due to increased zinc intake.¹ The levels of zinc that can impact copper absorption are measured at 18.5 mg/day or higher.¹ A high intake of copper is associated with less absorption of copper and high dietary iron is associated with a reduction of copper absorption.¹ Excess copper can cause iron deficiency.¹ Copper absorption is increased with the presence of amino acids such as histidine and cysteine, or the presence of binding ligands such as citrate.¹

Circulation: Copper is found bound to albumin or transcurprin in the blood. Once copper reaches the liver, it may reenter circulation with a-macroglobulin and ceruloplasmin.¹ These molecules transport copper to peripheral tissues and play a role in iron transport found in transferrin by acting as a ferroxidase (converts ferrous iron to ferric iron for transport on transferrin).¹

Storage and Excretion: Copper is found mostly within the liver but also in the heart, brain, kidneys, and spleen.¹ Excretion of copper occurs primarily in the bile but also in urine or through loss of skin and hair.¹

Functions: Copper serves as cofactors for many enzymes called cuproenzymes. 

Examples include:

Amine oxidases  (monoamine and diamine oxidase)  - break down amines such as tyramine, dopamine, serotonin, histidine, norepinephrine, and histamine.¹

Lysyl oxidase - a cuproenzyme responsible for deaminating lysine to form crosslinks that make collagen and elastin for connective tissue.¹

Cytochrome c oxidase - found within the electron transport chain as a rate-limiting enzyme dependent on copper content within tissues.¹

Dopamine hydroxylase - an enzyme that converts dopamine into norepinephrine dependent on copper.¹

Superoxide dismutase - A copper-zinc enzyme complex found within the brain, liver, thyroid, kidneys, and red blood cells that serves as a powerful antioxidant to destroy superoxide radicals.¹

Tyrosinase - A cuproenzyme responsible for the conversion of 1-DOPA into melanocytes. Lack of this enzyme can cause a noticeable loss in pigmentation.¹

Hydroxylase - an enzyme involved in tyrosine catabolism and containing copper.¹

Copper is also found as part of compounds such as protein transcuprin (plasma protein transporting copper), blood clotting factor V, and myelination of the nervous system.¹

Dietary Reference Intake (DRI) - The recommended dietary allowance (RDA) for copper is 900 micrograms for adult men and women 19 years old and older.²

Deficiency/Toxicity- Copper deficiency is not common among adults but can occur. Individuals who undergo bariatric surgery may not absorb copper as effectively.¹ Copper deficiency may be present in premature infants, malnourished infants, infants with short gut syndrome, and infants on enteral nutrition; they often present with brittle bones that can fracture easily.¹

Genetic conditions that can lead to a copper deficiency are Menkes disease and Wilson disease.¹ Menkes disease occurs when there is an error with protein ATP7A and causes depigmentation of skin, CNS damage, muscle/connective tissue abnormalities, and kinky hair.¹ Wilson disease leads to increased levels of copper in the liver and brain due to an abnormality with a protein called ATP7B; it leads to liver damage and neurological issues.¹

Dietary Sources of Copper

Copper is found within an assortment of foods - copper found in plants is dependent on the soil and water content of copper, and copper content in meat is dependent on the amount found in the animals' feed and water as well.¹ Copper can be found in foods such as nuts, chocolate, shellfish, organ meats, beans, and dried fruit.¹

Examples of foods containing copper include

Meat/Seafood/Animal Product-  beef liver, oysters, beef, crab, pork, turkey 

Legumes/Grains/Nuts - cereals, sunflower seeds, chickpeas, cashews, millet, pasta

Vegetables/Fruits - potatoes, mushrooms, spinach, asparagus, tomatoes, apples, figs

Dairy - milk, Greek yogurt

Source(s):

1. Denise M Medeiros and Robert E.C. Wildman, Advanced Human Nutrition, 4th ed. (Burlington, MA: Jones & Bartlett, 2019).

2. https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/