Haem

Question 1

Define Haem - including where the molecule is found and synthesis

Answer 1

Haem is a complex molecule formed from a porphyrin ring with a central Fe2+ molecule, which is capable of binding oxygen. The iron molecule is also capable of multiple oxidation states - facilitating binding.
This prosthetic group is incorporated into haemoglobin and cytochromes.
Haem is formed from glycine and succinyl-CoA, occurring in the mitochondria and cytoplasm. ALA synthase is the rate limiting step.

Question 2

Define anaemia

Answer 2

Decreased numbers of erythrocytes. Anaemia arises from a deficiency in haemoglobin leading to decreased oxygen transport capabilities and resultantly, decreased delivery of oxygen to tissues.

Question 3

Porphyria’s

Answer 3

Arises from a deficiency in haem synthesising enzymes..

Symptoms: Photosensitivity, dementia, diarrhoea

Question 4

Give examples of nutritional defects which result in decreased levels of haem

Answer 4

General nutrient deficits: Glycine and succinyl-CoA
Iron poor diet
Vitamin B6 deficiency (first coenzyme for haem synthesis)
Children, elderly and women are pre-disposed
Alcoholism: Often more instances of bleeding and vitamin B6 deficient

Question 5

Describe how mutations in haemoglobin result in anaemia

Answer 5

Lead to decreased oxygen carriage abilities, changes in shape, decreased production of RBCs

Question 6

Describe why the shape of haemoglobin is important

Answer 6

The concave disc shape of haemoglobin increases surface area.
Allows for co-operative binding and allosteric changes associated with oxygen binding.
Allows RBCs to transverse the blood vessels

Question 7

Explain how to diagnose a defect in haem synthesis

Answer 7

Analyse metabolic pathways.
Look for interruptions in flow (accumulation of metabolites) that may indicate a synthetic deficit/problem
May use gene sequencing

Question 8

Explain why toxins can result in decreased levels of haem

Answer 8

Detoxification requires use of cytochromes P450s, which require haem. Greater levels are haem are then required for CytP450 synthesis, leading less available for the synthesis of haemoglobin .
Toxins may bind to RBCs, causing immune recognition and lysis of the cells.

Question 9

Explain why decreased iron intake leads to decreased levels of Haem

Answer 9

Decreased availably of iron for the synthesis of haem, as iron is placed centrally within the porphyrin ring