Copper Article Takeaways

Question 0

Which two states can copper ions exist?

Answer 0

• oxidized, cupric (Cu2+)

- reduced, cuprous (Cu+)

Question 1

Where is the highest concentration of copper in the body found?

Answer 1

Liver

Question 2

Cu functions as a co-factor and is required for structural and catalytic properties of a variety of important enzymes including:

Answer 2

• cytochrome c oxidase
• tyrosinase
• p-hydroxyphenyl pyruvate hydrolase
• dopamine beta hydroxylase
• lysyl oxidase
• Cu-zinc superoxide dismutase (Cu-Zn-SOD)

Question 3

Which provides the most of the Cu consumed by mammals; food or water?

Answer 3

Food

Question 4

What are some copper rich foods?

Answer 4

• oysters
• liver
• nuts
• legumes
• whole grains
• dried fruit

Question 5

What percentage of average daily intake of drinking water contains copper? What is the EPA maximum contaminant level for Cu in drinking water?

Answer 5

6-13%; 1.3mg Cu/l

Question 6

From what sources is copper released into the air?

Answer 6

Natural: windblown dust, volcanoes, forest fires

Man-made: smelters, iron/steel production, and municipal incinerators

Question 7

Where is the 30-50% of ingested copper (mostly Cu2+) absorbed?

Answer 7

small intestine (with very small amounts being absorbed in the stomach)

Question 8

Which amino acids bind to Cu to allow absorption through an amino acid transport system?

Answer 8

Histidine, methionine, and cysteine

Question 9

Which other materials form ligands with Cu for ready absorption?

Answer 9

GSH (reduced glutathione), and organic acids: citric, gluconic, lactic, and acetic acids

Question 10

What metals/compounds impair Cu absorption?

Answer 10

• zinc
• iron
• molybdenum
• calcium
• phosphorus
• vitamin C

Question 11

What two materials bind to and transport Cu from the small intestine in the blood to the liver?

Answer 11

albumin and transcuprein

Question 12

Where is copper stored (cellularly), secreted into, or excreted in?

Answer 12

Hepatocytes of the liver; plasma; bile

Question 13

Cu held in the hepatocytes is mostly bound to what substance? Or it is synthesized into which substance?

Answer 13

metallothionein; cuproenzymes

Question 14

What is an acute phase protein that is the main Cu binding protein and contains 6 Cu atoms in both states (Cu2+ and Cu+)?

Answer 14

Ceruloplasmin

Question 15

What percentage of circulating Cu in the blood is in the form of ceruloplamin?

Answer 15

60-90%

Question 16

Cu released from the liver is primarily bound to which substance? What are 3 other materials to which it can bind?

Answer 16

ceruloplasmin; albumin, transcuprein, and histidine

Question 17

Why might metallothionein bind intracellular ionic Cu?

Answer 17

to prevent cytoxicity and serve as an antioxidant

Question 18

How much copper does the normal adult liver contain (by dry weight)? How much does blood contain?

Answer 18

18-45µg Cu/g; 6mg

Question 19

How does the body homeostatically regulate Cu? What is its primary method?

Answer 19

• increased Cu absorption or excretion - protects agains Cu toxicity or deficiency
• endogenous excretion is the primary method for regulating the body’s Cu stores

Question 20

Which route represents the major excretory pathway of Cu?

Answer 20

biliary (it accounts for 80% of the Cu leaving the liver)

Question 21

What is the amount of Cu lost daily through sweat? Urine?

Answer 21

Sweat: 50-100µg
Urine: 10-50µg

Question 22

What is the 2002 Dietary Reference Intake for Cu daily for adults? What is the W.H.O. recommendation for men/women (adults)?
What is the average daily intake?

Answer 22

• 0.9mg/daily
• women: 0.6mg/daily and men: 0.7mg/daily
• 1mg/daily

Question 23

Cu in normal healthy adults is linked to prosthetic groups or tightly bound in storage or transport proteins, so it is typically not available for participation in which reactions?

Answer 23

Oxidation

Question 24

How is copper used in daily areas and what does this cause?

Answer 24

metal or alloy in machinery, construction, transportation, military weaponry, component of white gold, alloys for imitation jewelry, dental products, cosmetics, IUD. -While not harmful upon exposure, chronic exposure or elevated exposure is damaging

Question 25

Chronic Cu toxicity primarily affects which organ?

Answer 25

Liver

Question 26

Cu toxicity is typically manifested by the development of what condition? Accompanied by what other symptoms?

Answer 26

liver cirrhosis; episodes of hemolysis, damage to renal tubules, brain and other organs, resulting in coma, hepatic necrosis, vascular collapse, and death

Question 27

What are 3 areas where Cu was found to be causing toxicity?

Answer 27

- Dialysis patients (through Cu tubing) - Workers using pesticides containing Cu - Infants maintained for long period of time on IV total parenteral nutrition

Question 28

Consuming Cu-contaminated water or food is associate with development of acute _________ symptoms, but NOT with increase mortality from liver disease.

Answer 28

gastrointestinal

Question 29

Cu poisoning may result in what early stage symptoms?

Answer 29

- weakness, lethargy, and anorexia - as well as: erosion of the epithelial lining of GI tract, heptocellular necrosis in the liver, and acute tubular necrosis in the kidney

Question 30

What is the estimated lethal dose of Cu in an untreated adult?

Answer 30

10-20g

Question 31

What animals can tolerate many times their usual daily intakes of Cu?

Answer 31

Rodents, poultry, and pigs.

Question 32

Which animals are sensitive to high Cu intakes?

Answer 32

- sheep - Bedlington terriers - Long-Evans Cinnamon strain rats

Question 33

What medical conditions predispose patients to increased Cu concentrations?

Answer 33

primary biliary cirrhosis, obstructive hepatobiliary disease, extrahepatic biliary atresia, neonatal hepatitis, choledochal cysts and a-1-antitrypsin deficiency

Question 34

Which Cu-dependent disorders provide a rationale for a link between severely dysregulated metal-ion homeostasis and selective pathology?

Answer 34

Menkes syndrome and Wilson's disease

Question 35

Which syndrome is an X-linked Cu deficiency disorder that is usually fatal in early childhood?

Answer 35

Menkes syndrome

Question 36

Which disorder presents with mental retardation and neruodegeneration (mostly as a result of a deficiency of Cu-dependent enzymes necessary for brain development)?

Answer 36

Menkes syndrome

Question 37

Which disease is an autosomal recessive metabolic disorder characterized by a marked increase of Cu in the liver and brain due to a reduced capacity for biliary and other means of Cu excretion?

Answer 37

Wilson's disease

Question 38

An alteration in the ATP7B gene on chromosome 13 affects which enzyme? For which process is the enzyme key?

Answer 38

Cu-transporting enzyme, adenosine triphosphatase; key to excretion of Cu into the bile

Question 39

Dysfunction with the enzyme adenosine triphosphatase will result in what problem?

Answer 39

- Accumulation of Cu in hepatocytes | - Cu builds in the liver leading to cirrhosis

Question 40

Patients with Wilson's disease have evidence of what reaction in their liver mitochondria and a reduced liver and blood concentration of the antioxidant Vitamin _____ suggesting the role of Cu in what type of damage?

Answer 40

lipid peroxidation; Vit E; oxidative damage

Question 41

What are the treatments for Wilson's disease?

Answer 41

D-penicillamine (1g/day) and oral Zn supplement (which compete for Cu)

Question 42

What are two conditions that mimic Wilson's disease?

Answer 42

- Idiopathic Cu toxicosis | - Indian Childhood Cirrhosis

Question 43

What are the major differences of Idiopathic Cu toxicosis and Wilson's?

Answer 43

- abnormally high levels of hepatic Cu - normal or increased plasma concentrations of Cu and ceruloplasmin - clinical onset and cirrhosis by age 2, death by age 5

Question 45

What is the mechanism for Cu damage in the body?

Answer 45

Free Cu ions participate in formation of ROS

Question 46

In the presence of superoxide (*O2-) or reducing agents such as ascorbic acid or GSH, Cu2+ can be reduced to Cu+ which is capable of what?

Answer 46

catalyzing the formation of hydroxyl radicals (OH*) from hydrogen peroxide (H2O2) via the Haber-Weiss reaction

Question 47

What does the hydroxyl radical do that is so bad?

Answer 47

It can initiate oxidative damage by abstracting the H+ from an amino-bearing carbon to form a carbon-centered protein radical and from an unsaturated fatty acid to form a lipid radical.

Question 51

What are characteristics of Indian childhood cirrhosis that distinguish it from Wilson's disease? What can help?

Answer 51

- Increased Cu in the blood but normal ceruloplasmin concentrations and very high Cu concentrations in the liver - Treatment with D-pencillamine prevents a fatal outcome and often restores liver histology to normal