Copper Article Takeaways Flashcards

0
Q

Which two states can copper ions exist?

A
  • oxidized, cupric (Cu2+)

- reduced, cuprous (Cu+)

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1
Q

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

A

Liver

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2
Q

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

A
  • cytochrome c oxidase
  • tyrosinase
  • p-hydroxyphenyl pyruvate hydrolase
  • dopamine beta hydroxylase
  • lysyl oxidase
  • Cu-zinc superoxide dismutase (Cu-Zn-SOD)
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3
Q

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

A

Food

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4
Q

What are some copper rich foods?

A
  • oysters
  • liver
  • nuts
  • legumes
  • whole grains
  • dried fruit
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5
Q

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

A

6-13%; 1.3mg Cu/l

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6
Q

From what sources is copper released into the air?

A

Natural: windblown dust, volcanoes, forest fires

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

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7
Q

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

A

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

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8
Q

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

A

Histidine, methionine, and cysteine

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9
Q

Which other materials form ligands with Cu for ready absorption?

A

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

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10
Q

What metals/compounds impair Cu absorption?

A
  • zinc
  • iron
  • molybdenum
  • calcium
  • phosphorus
  • vitamin C
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11
Q

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

A

albumin and transcuprein

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12
Q

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

A

Hepatocytes of the liver; plasma; bile

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13
Q

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

A

metallothionein; cuproenzymes

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14
Q

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

A

Ceruloplasmin

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15
Q

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

A

60-90%

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16
Q

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

A

ceruloplasmin; albumin, transcuprein, and histidine

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17
Q

Why might metallothionein bind intracellular ionic Cu?

A

to prevent cytoxicity and serve as an antioxidant

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18
Q

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

A

18-45µg Cu/g; 6mg

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19
Q

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

A
  • increased Cu absorption or excretion - protects agains Cu toxicity or deficiency
  • endogenous excretion is the primary method for regulating the body’s Cu stores
20
Q

Which route represents the major excretory pathway of Cu?

A

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

21
Q

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

A

Sweat: 50-100µg
Urine: 10-50µg

22
Q

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?

A
  • 0.9mg/daily
  • women: 0.6mg/daily and men: 0.7mg/daily
  • 1mg/daily
23
Q

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?

A

Oxidation

24
Q

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

A

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

25
Q

Chronic Cu toxicity primarily affects which organ?

A

Liver

26
Q

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

A

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

27
Q

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

A
  • Dialysis patients (through Cu tubing)
  • Workers using pesticides containing Cu
  • Infants maintained for long period of time on IV total parenteral nutrition
28
Q

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

A

gastrointestinal

29
Q

Cu poisoning may result in what early stage symptoms?

A
  • 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
30
Q

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

A

10-20g

31
Q

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

A

Rodents, poultry, and pigs.

32
Q

Which animals are sensitive to high Cu intakes?

A
  • sheep
  • Bedlington terriers
  • Long-Evans Cinnamon strain rats
33
Q

What medical conditions predispose patients to increased Cu concentrations?

A

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

34
Q

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

A

Menkes syndrome and Wilson’s disease

35
Q

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

A

Menkes syndrome

36
Q

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

A

Menkes syndrome

37
Q

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?

A

Wilson’s disease

38
Q

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

A

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

39
Q

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

A
  • Accumulation of Cu in hepatocytes

- Cu builds in the liver leading to cirrhosis

40
Q

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?

A

lipid peroxidation; Vit E; oxidative damage

41
Q

What are the treatments for Wilson’s disease?

A

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

42
Q

What are two conditions that mimic Wilson’s disease?

A
  • Idiopathic Cu toxicosis

- Indian Childhood Cirrhosis

43
Q

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

A
  • 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
45
Q

What is the mechanism for Cu damage in the body?

A

Free Cu ions participate in formation of ROS

46
Q

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?

A

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

47
Q

What does the hydroxyl radical do that is so bad?

A

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.

51
Q

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

A
  • 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