3. Haemoglobin Flashcards
Difference between myoglobin and haemoglobin
Mb is a storage protein
Binds O2 quickly but dissociates slowly
Not co-operative
1 polypeptide
Structure of haemoglobin
4 polypeptide chains
Each chain has a haem group
Can bind 4 oxygen
Subunits held together by non-covalent interactions
Explain what is meant by cooperativity
Binding of one O2 increases the affinity of other haem groups
Allows Hb to deliver more oxygen
Due to haem interactions
Describe the structural change in haemoglobin due to oxygenation
In deoxy- Hb the subunits are held together by 8 salt bridges
Contact region is connected to the haem groups
Movement of the haem group causes Hb to be less constrained
What is the Bohr effect?
O2 is released more easily at low pH or increased pCO2
What is 2,3- BPG?
2,3- biphosphoglycerate
By-product of glycolysis
What does 2,3-BPG do?
Binds to deoxy-Hb
Decreases its affinity for O2
How does 2,3-BPG decrease Hb affinity?
Has 4 negative charges
Forms salt bridges with positive residues
Hb where 2,3-BPG has been removed has high O2 affinity
What happens when 2,3-BPG levels are elevated?
Reduced affinity allows Hb to release O2 efficiently to tissues
What is the cause of sickle cell anaemia?
Point mutation on Hb beta globin chain which forms a ‘sticky patch’ in low O2
Glutamate to valine
Clinical consequences of sickle cell anaemia
Bone pain, chronic anaemia, organ damage
What does hydroxyurea do?
Increases fetal haemoglobin levels
What happens in a G6PD deficiency?
Means less NADPH in RBCs
Causes oxidative damage
RBCs are cleared more rapidly
How is sickle cell anaemia treated?
Treat symptoms
Hydration, painkillers, antibiotics
Blood transfusion
Hydroxyurea
What are precipitating factors in G6PD deficiency?
Oxidant drugs
Eating fava beans
Infection
Neonatal jaundice
