Copper

Katrina Beining & Sarah StahlFN 4320

Overview

• Atomic number is 29 and molecular weight is 63.55g/mol

• Atomic symbol: Cu• Two valence states: cupric (Cu2+) & cuprous

(Cu1+)• Cupric=oxidized; cuprous=reduced• Only about 150mg copper is found in the body

[1]

Overview Continued

• Main storage site of copper is the liver• Liver helps to maintain copper homeostasis• Skeleton contains the highest percent of

copper• Binds to metallothionein protein in cells

(stores 12 copper and 12 zinc molecules) [1]

Needs

• Trace mineral, but still important• RDA for copper is 900µg/day• UL for copper is 10,000µg/day [2]• Most people meet their copper needs,

concern of deficiencies in developing nations• Bioavailability: 12-75% [3]

Good Sources

• Highest levels in dried fruits, dried legumes, and organ meats [2]

• Shellfish, whole grains, potatoes, and dark leafy greens are also good sources [4]

• Drinking water can be a source that often leads to toxicity (copper pipes leaching into potable water)

Good Sources Cont.

http://www.sparknotes.com/health/minerals/minor/section3.rhtml

Functions

• Important in functioning of organs & metabolic processes

- Bone health (cross-linking of collagen & turnover of bone tissue), CNS, immune system, CV system, reproduction, skin health, gene transcription [5,6,7]

- Endorphin action [1]• Builds tissue, maintains blood volume, and

produces energy• Produces RBCs and collagen [8]

Functions Continued

• Bound copper acts as an antioxidant, free copper is a free radical [9]

• Proteins that incorporate copper include: cytochrome c oxidase, ceruloplasmin, dopamine, blood clotting proteins, and many others [1,10]

• Cofactor of superoxide dismutase (part of antioxidant defense system) [2]

• Copper-dependent enzymes, cuproenzymes, function in cellular respiration, peptide hormone processing, neurotransmitter production, skin & hair pigment synthesis, and connective tissue [6,11]

Metabolism

http://www.weblo.com/celebrity/available/Ophelia_Kolb/500280/

Methods of Measuring Copper Status

• Current:- ceruloplasmin (serum copper)= not a good

indicator b/c of differences in metabolism & $$$$ [9]

- hair, saliva, feces, hair, urine= not accurate - plasma copper concentration, superoxide

dismutase activity, & platelet copper concentration- not accurate independently

- platelet copper concentration is best method b/c of sensitivity to small changes [11]

Limitations to Current Measuring Methods

• plasma copper & ceruloplasmin- not sensitive enough; detect low levels only when body is severely deficient, also effected by several factors (gender, age, diseases, pregnancy, etc.)

• Erythrocyte superoxide dismutase- same problems, but especially in Down’s syndrome & alcoholism patients

• Ratio of ceruloplasmin enzymatic activity to cupric immunoreactive protein concentration & non-ceruloplasmin-bound copper level- less interference from disease states, but calculations lead to human error [11]

Possible New Biomarkers of Copper Status

• Cuproenzymes (cytochrome c oxidase-CCO, peptidylglycine alpha-amidating monooxygenase-PAM, superoxide dismutase3- SOD3, diamine oxidase-DAO, & lysyl oxidase)

• Copper-trafficking proteins- certain copper-trafficking protein levels are more

sensitive than current methods• Immune & bone markers

- pyridinoline (PYD) & deoxypyridinoline (DPD) are cross links of bone collagen which show in urine when bone degrades from copper deficiency [11]

Toxicity• High levels of copper is toxic to the body• Contaminated water is the main source [1]• Occupational copper exposure is another problem- inhaled copper

dust leads to respiratory problems, headaches, nausea, diarrhea, GI issues, & fever [9]

• Related to higher cancer rates (esp. CRC), erythrocyte, liver, and eye damage

• High blood copper levels found in people with rheumatoid arthritis, thalassemia, & sickle-cell anemia [10]

• Might be linked to Alzheimer’s disease- studies contradicting [11]• If left untreated, high copper levels result in organ failure, shock,

coma, and death

Wilsons’ Disease

• Rare genetic disorder that causes copper deposits to form in the brain, liver, and other organs

• Genetic mutation disturbs the protein that takes excess copper out of the liver

• High liver accumulation characteristic of Wilsons’ also present in Indian childhood cirrhosis and endemic Tyrolean infantile cirrhosis [11]

http://www.studyblue.com/notes/note/n/alcoholic-liver-disease-metabolic-liver-diseases-biliary-tract-diseases/deck/1823677

http://coneil283.wordpress.com/2011/12/02/copper-its-not-just-for-pennies/

http://www.eurowilson.org/en/living/guide/pregnancy/index.phtml

Deficiency- Hypocupraemia

• Fairly rare• Populations at high risk: premature infants, children with

malnutrition, elderly, people with disorders that effect absorption in GI tract, pregnant and lactating women, vegetarians, and people recovering from illness [2]

• Taking certain meds over long periods of time can increase chance of deficiency [1]

• Common in burn victims [6]• Main symptoms: anemia, iron deficiency, low neutrophil

count in the blood, bone malformations, stunted growth, impaired immunity, & hypopigmentation of hair and skin [11]

Diseases Related to Deficiency

• Menkes syndrome- results from malabsorption in intestines

- occipital horn syndrome is a more mild form characterized by connective tissue and skeletal deformities [11]

• Copper deficiency might be a cause of organ damage in diabetes, but improved cardiac function [12]

Interactions

• Iron- low copper results in iron trapped in cells, leading to anemia [1]

• Molybdenum- enhances copper excretion in urine [13]

• Zinc- higher zinc=lower copper absorption; methallothionein transports both zinc & copper resulting in retention of copper in enterocytes & decreased absorption [3]

Excretion

• Major pathway is through bile in feces• Regulated by liver to maintain homeostasis• Also excreted through urine; amount in urine

is similar from day to day but amount in feces changes based on intake

• Small amount excreted in hair, nails, skin cells, semen, and menses [1]

Excretion Cont.

http://www.eurowilson.org/en/living/guide/pathway/index.phtml

Conclusion

• Essential for healthy body- but only small amounts needed• Good sources• Toxicity leads to oxidative damage, cancer, and kidney and

liver failure• Deficiency leads to anemia, skeletal deformations, stunted

growth, discolored hair and skin, etc. • Several different biomarkers are looked at to assess copper

status in the body• Much is still unknown about copper’s functions• The need for an accurate, sensitive test for copper levels is

evident

References1. Gropper SS, Smith S. Advanced nutrition and human metabolism, 6th ed. Wadsworth: Cengage Learning ; 2013.2. Velasco-Reynold C, Navarro-Alarcon M, Lopez-G De La Serrana H, Lopez-Martinez M. Copper in foods, beverages and waters from south east spain: influencing factors and daily dietary intake by the andalusian population. Food Addit Contam. 2008 Aug; 25(8):937-945.3. Dietary reference intakes for vitamin a, vitamin k, arsenic, boron, chromium, copper, idoine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press; 2001. 4. Trumbo P, Yates AA, Schlicker S, Poos M. Food and Nutrition Board, Institute of Medicine, The National Academies. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc. 2001 Mar;101(3):294-301.5 . Jegede A, Oduguwa O, Bamgbose A, Fanimo A, Nollet L. Growth response, blood characteristics and copper accumulation in organs of broilers fed on diets supplemented with organic and inorganic dietary copper sources. British Poultry Science 2011;52(1):133-139. Available from: Academic Search Complete.6. Voruganti V, Klein G, Hong-Xing L, Thomas S, Freeland-Graves J, Herndon D. Impaired zinc and copper status in children with burn injuries: need to reassess nutritional requirements. Burns. 2005 Apr; 31:711-716.7. Copper Development Association Incorporated [internet]. 2013. Available from: http://www.copper.org/consumers/health/.8. Wojciak R. Effect of food restriction diets on copper concentration and copper/zinc ratio in tissues of female Wistar rats (animal anorexia model). Trace Elements & Electrolytes. 2013;30(4):185-190. 9. Saha A, Karnik A, Sathawara N, Kulkarni P, Singh V. Ceruloplasmin as a marker of occupational copper exposure. J Expo Sci Env Epid. 2008; 18:332-337.10. Zelenina M, Tritto S, Bondar A, Zelenin S, Aperia A. Copper inhibits the water and glycerol permeability of aquaporin-3. J Biol Chem. 2004 Dec; 279(50):51939-51943. 11. Bertinato J, Zouzoulas A. Considerations in the development of biomarkers of copper status. J AOAC Int. 2009; 92(5):1541-1550.12. Jun L, Pontré B, Pickup S, Choong S, Mingming L, Cooper G, et al. Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment. Cardiovascular Diabetology 2013; 12(1): 1-14. Available from: Academic Search Complete.13. Turnlund J. Copper nutriture, bioavailability, and the influence of dietary factors. J Am Diet Assoc. 1988; 88:303-308.