Iron Metabolism

Question 1

What does the ratio of haem and zinc protoporphyrin tell us?

Answer 1

If iron deficient, bone marrow inserts zinc into protporphyrin 9 (normally last step of Haem synthesis) –> zinc protoporphyrin complex.

Question 2

What is serum TfR useful for?

Answer 2

After reticulocyte differentiation - TfR cleaved from cell surface - gives measure of rate of erythropoiesis.

Question 3

How do serum TfR levels change in iron deficiency anaemia?

Answer 3

sTfR increases
Anaemia –> hypoxia which stimulates EPO –> increases rate of erythropoiesis.
Small pale RBCs seen as synthesis increases but not enough iron.

Question 4

What happens in the absence of hepcidin?

Answer 4

Free iron release from intestine and macrophages. (affects release of iron from dietary absorption and recycling pathway).

Question 5

Give four conditions associated with iron deficiency.

Answer 5

• Pathological blood loss (hookworm)
• Infection (overproduction of hepcidin)
• Pregnancy - more plasma but same no of RBS –> haemodilution.
• Obesity = haemodilution and chronic low grade inflammation.

Question 6

UK prevalence 2012.

Answer 6

Men and boys - 100% RNI, Girl (11-18) - only over half meet requirment.

Lower RNI ( baseline amount) - Men and boys - 1.5% consume below.
Girls (11-18) - almost half consume below.
9% of girls anaemic, 10% of women.

Question 7

What are the non-hepcidin mediated local iron absorption mechanisms?

Answer 7

• Dietary iron (DMT1 and DCyt trafficked away from membrane to vesicles under high iron load).
• Systemic iron - transcriptional (HIF2a) post-transcriptional (IRP2)
• Dietary factors - solubility and bioavailability.

Question 8

What experiments have shown a role for hypoxia in iron absorption?

Answer 8

(2012) - expose Caco-2 cells to hypoxia for 24hrs
- HIF2a increases and so does DMT1 and GLUT1.
mRNA of DMT1 increases.

(2009) - HIF1 or 2 KOs in mice.
HIF2 KO –> reduction in DMT1, DCytB, FPn (no effect on GLUT1).

Question 9

What is the effect of an IRP binding to a protein with a 3’ UTR?
Which iron proteins have 3’ IREs?
Are these transcribed under low or high iron?

Answer 9

Blocks endonuclease site –> protects from degradation.
Tf, DMT-1.
Low iron as IRP2 is synthesised under these conditions.

Question 10

Why is the optimal uptake of iron in the duodenum?

Answer 10

DMT1 is a proton couples transporter that needs an extracellular proton source.