Copper Article Takeaways Flashcards
Which two states can copper ions exist?
- oxidized, cupric (Cu2+)
- reduced, cuprous (Cu+)
Where is the highest concentration of copper in the body found?
Liver
Cu functions as a co-factor and is required for structural and catalytic properties of a variety of important enzymes including:
- cytochrome c oxidase
- tyrosinase
- p-hydroxyphenyl pyruvate hydrolase
- dopamine beta hydroxylase
- lysyl oxidase
- Cu-zinc superoxide dismutase (Cu-Zn-SOD)
Which provides the most of the Cu consumed by mammals; food or water?
Food
What are some copper rich foods?
- oysters
- liver
- nuts
- legumes
- whole grains
- dried fruit
What percentage of average daily intake of drinking water contains copper? What is the EPA maximum contaminant level for Cu in drinking water?
6-13%; 1.3mg Cu/l
From what sources is copper released into the air?
Natural: windblown dust, volcanoes, forest fires
Man-made: smelters, iron/steel production, and municipal incinerators
Where is the 30-50% of ingested copper (mostly Cu2+) absorbed?
small intestine (with very small amounts being absorbed in the stomach)
Which amino acids bind to Cu to allow absorption through an amino acid transport system?
Histidine, methionine, and cysteine
Which other materials form ligands with Cu for ready absorption?
GSH (reduced glutathione), and organic acids: citric, gluconic, lactic, and acetic acids
What metals/compounds impair Cu absorption?
- zinc
- iron
- molybdenum
- calcium
- phosphorus
- vitamin C
What two materials bind to and transport Cu from the small intestine in the blood to the liver?
albumin and transcuprein
Where is copper stored (cellularly), secreted into, or excreted in?
Hepatocytes of the liver; plasma; bile
Cu held in the hepatocytes is mostly bound to what substance? Or it is synthesized into which substance?
metallothionein; cuproenzymes
What is an acute phase protein that is the main Cu binding protein and contains 6 Cu atoms in both states (Cu2+ and Cu+)?
Ceruloplasmin
What percentage of circulating Cu in the blood is in the form of ceruloplamin?
60-90%
Cu released from the liver is primarily bound to which substance? What are 3 other materials to which it can bind?
ceruloplasmin; albumin, transcuprein, and histidine
Why might metallothionein bind intracellular ionic Cu?
to prevent cytoxicity and serve as an antioxidant
How much copper does the normal adult liver contain (by dry weight)? How much does blood contain?
18-45µg Cu/g; 6mg
How does the body homeostatically regulate Cu? What is its primary method?
- increased Cu absorption or excretion - protects agains Cu toxicity or deficiency
- endogenous excretion is the primary method for regulating the body’s Cu stores
Which route represents the major excretory pathway of Cu?
biliary (it accounts for 80% of the Cu leaving the liver)
What is the amount of Cu lost daily through sweat? Urine?
Sweat: 50-100µg
Urine: 10-50µg
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?
- 0.9mg/daily
- women: 0.6mg/daily and men: 0.7mg/daily
- 1mg/daily
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?
Oxidation
How is copper used in daily areas and what does this cause?
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
Chronic Cu toxicity primarily affects which organ?
Liver
Cu toxicity is typically manifested by the development of what condition? Accompanied by what other symptoms?
liver cirrhosis; episodes of hemolysis, damage to renal tubules, brain and other organs, resulting in coma, hepatic necrosis, vascular collapse, and death
What are 3 areas where Cu was found to be causing toxicity?
- Dialysis patients (through Cu tubing)
- Workers using pesticides containing Cu
- Infants maintained for long period of time on IV total parenteral nutrition
Consuming Cu-contaminated water or food is associate with development of acute _________ symptoms, but NOT with increase mortality from liver disease.
gastrointestinal
Cu poisoning may result in what early stage symptoms?
- 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
What is the estimated lethal dose of Cu in an untreated adult?
10-20g
What animals can tolerate many times their usual daily intakes of Cu?
Rodents, poultry, and pigs.
Which animals are sensitive to high Cu intakes?
- sheep
- Bedlington terriers
- Long-Evans Cinnamon strain rats
What medical conditions predispose patients to increased Cu concentrations?
primary biliary cirrhosis, obstructive hepatobiliary disease, extrahepatic biliary atresia, neonatal hepatitis, choledochal cysts and a-1-antitrypsin deficiency
Which Cu-dependent disorders provide a rationale for a link between severely dysregulated metal-ion homeostasis and selective pathology?
Menkes syndrome and Wilson’s disease
Which syndrome is an X-linked Cu deficiency disorder that is usually fatal in early childhood?
Menkes syndrome
Which disorder presents with mental retardation and neruodegeneration (mostly as a result of a deficiency of Cu-dependent enzymes necessary for brain development)?
Menkes syndrome
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?
Wilson’s disease
An alteration in the ATP7B gene on chromosome 13 affects which enzyme? For which process is the enzyme key?
Cu-transporting enzyme, adenosine triphosphatase; key to excretion of Cu into the bile
Dysfunction with the enzyme adenosine triphosphatase will result in what problem?
- Accumulation of Cu in hepatocytes
- Cu builds in the liver leading to cirrhosis
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?
lipid peroxidation; Vit E; oxidative damage
What are the treatments for Wilson’s disease?
D-penicillamine (1g/day) and oral Zn supplement (which compete for Cu)
What are two conditions that mimic Wilson’s disease?
- Idiopathic Cu toxicosis
- Indian Childhood Cirrhosis
What are the major differences of Idiopathic Cu toxicosis and Wilson’s?
- 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
What is the mechanism for Cu damage in the body?
Free Cu ions participate in formation of ROS
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?
catalyzing the formation of hydroxyl radicals (OH*) from hydrogen peroxide (H2O2) via the Haber-Weiss reaction
What does the hydroxyl radical do that is so bad?
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.
What are characteristics of Indian childhood cirrhosis that distinguish it from Wilson’s disease? What can help?
- 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
