Iron and Copper - Skildum

Question 1

What does the Creatinine Height Index (CHI) measure?

Answer 1

Nutritional status

Question 2

What is the reduced form of iron?

Answer 2

Fe²⁺

(favored in low pH)

Question 3

What is the oxidized form of iron?

Answer 3

Fe³⁺

(converted by ceruloplasmin)

Question 4

Iron transport in the blood requires what form of iron?

Answer 4

Iron transport in the blood requires oxidation to Fe³⁺ by hephaestin (HP; ceruloplasmin).

This is a copper requiring enzyme.

Question 5

What form of iron is absorbed in the intestines?

Answer 5

At the brush border, a reductase reduces ferric iron to ferrous iron.

Fe²⁺ then is transported through the divalent metal transporter -1 (DMT1).

Question 6

What does iron bind to for transport to the tissues?

Answer 6

Fe³⁺ binds transferritin for transport to tissues.

Question 7

Where is the main storage of iron in the body?

Answer 7

• Liver:
  
  • Ferritin (Fe³⁺)⇔ Hemosiderin

Question 8

Regulation of iron uptake is through what?

Answer 8

hepcidin

When iron stores in the liver are high, hepcidin is produced.

It binds ferroportin (FPN) and causes its degradation.

Question 9

What are the functions of Iron?

Answer 9

• 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

Question 10

What vitamin enhances the absorption of iron?

Answer 10

Vitamin C enhances absorption and maintains iron in the reduced state.

Question 11

Iron inhibits the absorption of what mineral?

Answer 11

Iron inhibits zinc absorption.

Question 12

What is required for the export of iron from enterocytes?

Answer 12

Copper is required for export of iron from enterocytes.

Question 13

Iron deficiency most often occurs in what patient demographics?

Answer 13

• Observed in:
  
  • infants (low iron in diets)
  • adolescents (rapid growth rate)
  • pregnant women (rapid growth rate, blood loss at delivery)
  • absorption disorders

Question 14

What are the symptoms of iron deficiency?

Answer 14

Microcytic hypochromic anemia, listlessness, fatigue

Question 15

What happens if iron intake exceeds the livers ferritin storage capacity?

Answer 15

• can accumulate in tissues and act as a free radical → causing oxidative damage
  
  • Iron toxicity: TUL = 45 mg / day

Question 16

What happens in Chronic hemochromotosis, which is caused by inherited mutations in hepcidin (or other iron metabolism genes)?

Answer 16

It causes organ failure due to iron accumulation.

Question 17

What are the dietary sources of copper?

Answer 17

meat, shellfish, and nuts

Question 18

How is copper absorbed in the intestines?

Answer 18

• A brush border reductase reduces Cu²⁺ to Cu⁺.
• Cu⁺ then is transported through CTR1.

Question 19

How does copper enter the blood stream?

Answer 19

• Cu⁺ enters the blood through ATP7A
  
  • a basolateral transporter
  • circulates bound to proteins
    
    • e.g. albumin

Question 20

What causes Menkes kinky hair syndrome?

Answer 20

• 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

Question 21

What are the functions of copper?

Answer 21

• 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.

Question 22

What causes copper deficiency?

Answer 22

• May occur in people who consume a lot of zinc, or a lot of proton pump inhibitors

Question 23

What are the symptoms of Copper Deficiency?

Answer 23

Symptoms: anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism.

Question 24

What are the symptoms of acute and chronic Copper Toxicity?

Answer 24

• Copper toxicity: TUL = 10 mg/day
• acute: epigastric pain, nausea, vomiting, diarrhea
• chronic: hematuria, liver damage, kidney damage

Question 25

What is Wilson Disease caused by? How do you treat it?

Answer 25

• 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.