Iron and Copper - Skildum Flashcards
What does the Creatinine Height Index (CHI) measure?
Nutritional status
What is the reduced form of iron?
Fe2+
(favored in low pH)
What is the oxidized form of iron?
Fe3+
(converted by ceruloplasmin)
Iron transport in the blood requires what form of iron?
Iron transport in the blood requires oxidation to Fe3+ by hephaestin (HP; ceruloplasmin).
This is a copper requiring enzyme.
What form of iron is absorbed in the intestines?
At the brush border, a reductase reduces ferric iron to ferrous iron.
Fe2+ then is transported through the divalent metal transporter -1 (DMT1).
What does iron bind to for transport to the tissues?
Fe3+ binds transferritin for transport to tissues.
Where is the main storage of iron in the body?
- Liver:
- Ferritin (Fe3+)⇔ Hemosiderin
Regulation of iron uptake is through what?
hepcidin
When iron stores in the liver are high, hepcidin is produced.
It binds ferroportin (FPN) and causes its degradation.
What are the functions of Iron?
- Heme synthesis:
- Glycine + succinyl CoA + Iron à heme
- Heme is used in:
- cytochrome B, cytochrome C
- hemoglobin, myoglobin
- monooxygenases, e.g. phenylalanine dehdrogenase
- Iron-Sulfur clusters:
- Electron transfer groups in, e.g. NADH dehydrogenase
- Non-heme iron:
- Dioxygenase, e.g. homogentisate dioxygenase
What vitamin enhances the absorption of iron?
Vitamin C enhances absorption and maintains iron in the reduced state.
Iron inhibits the absorption of what mineral?
Iron inhibits zinc absorption.
What is required for the export of iron from enterocytes?
Copper is required for export of iron from enterocytes.
Iron deficiency most often occurs in what patient demographics?
- Observed in:
- infants (low iron in diets)
- adolescents (rapid growth rate)
- pregnant women (rapid growth rate, blood loss at delivery)
- absorption disorders
What are the symptoms of iron deficiency?
Microcytic hypochromic anemia, listlessness, fatigue
What happens if iron intake exceeds the livers ferritin storage capacity?
- can accumulate in tissues and act as a free radical → causing oxidative damage
- Iron toxicity: TUL = 45 mg / day
What happens in Chronic hemochromotosis, which is caused by inherited mutations in hepcidin (or other iron metabolism genes)?
It causes organ failure due to iron accumulation.
What are the dietary sources of copper?
meat, shellfish, and nuts
How is copper absorbed in the intestines?
- A brush border reductase reduces Cu2+ to Cu+.
- Cu+ then is transported through CTR1.
How does copper enter the blood stream?
- Cu+ enters the blood through ATP7A
- a basolateral transporter
- circulates bound to proteins
- e.g. albumin
What causes Menkes kinky hair syndrome?
- by mutations in ATP7A
- characterized by hypothermia, hypotonia, poor feeding, failure to thrive, and seizures.
- patients have normal hair at birth, but it becomes brittle and sparse as they age
What are the functions of copper?
- Cofactor for ceruloplasmin
- Cytochrome C oxidase has 3 Cu+ per enzyme
- Cofactor for lysyl oxidase
- (collagen synthesis; also requires ascorbate)
- Copper is a cofactor for superoxide dismutase, an antioxidant enzyme.
- Copper is a cofactor for dopamine b-hydroxylase, required for catecholamine synthesis.
What causes copper deficiency?
- May occur in people who consume a lot of zinc, or a lot of proton pump inhibitors
What are the symptoms of Copper Deficiency?
Symptoms: anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism.
What are the symptoms of acute and chronic Copper Toxicity?
- Copper toxicity: TUL = 10 mg/day
- acute: epigastric pain, nausea, vomiting, diarrhea
- chronic: hematuria, liver damage, kidney damage
What is Wilson Disease caused by? How do you treat it?
- mutation in the liver specific copper transporter ATP7B
- ATP7B normally transports excess copper into the bile for excretion
- When it is defective, copper accumulates and ‘leaks out’ unbound to ceruloplasmin
- Treatment is to avoid high copper foods, and chelation therapy.
