Haemoglobin and Myoglobin Flashcards
Briefly describe the structure of a haem group.
In a haem group, there is a protoporphyrin ring, with an Fe bound to 4 N within the ring. The Fe group can bind to one O2 molecule, whilst the other side is bound to the protein by a histidine residue (proximal histidine)
Why is there a difference in structure between deoxy and oxy myoglobin/ haemoglobin.
In the deoxy form, the Fe molecule sits below the plane within the haem group, however when it binds to oxygen it is pulled into the centre of the ring. This has an impact on the histidine residue the other side and leads to a conformational change.
What is the difference between the binding of oxygen to both myoglobin and haemoglobin and how does this affect the shape of the graph?
Myoglobin has a constant affinity for oxygen and so it readily accepts it (it shows an exponential curve). Haemoglobin has a changing binding affinity and so the graph is curved.
What are the two states that deoxy haemoglobin can exist in?
High affinity R state
Low affinity T state
How does the binding of one oxygen molecule to haemoglobin alter the binding of subsequent molecules?
When one molecule binds, it stabilises the high affinity state, and so promotes the binding of subsequent molecules.
Why is the sigmoidal curve of haemoglobin important for its function?
It means that where pO2 is high (lungs) Haemoglobin will take up oxygen, and where is it low (muscles/cells) Haemoglobin will release its oxygen.
What is the action of 2,3-BPG on haemoglobin?
It lowers the affinity of haemoglobin for oxygen meaning that more oxygen is released at tissues where BPG is high. It shifts the curve to the right.
What is the BOHR effect?
The BOHR effect is the effect of pH on haemoglobin. An increase in pH will shift the curve to the right, lowering the affinity of Haemoglobin. This is important in metabolically active tissues where there are higher concentrations of H+/CO2.
Why is Carbon monoxide poisoning a problem?
CO binds to haemoglobin very tightly, and will not be released. If 4CO molecules bind to a haemoglobin it can no longer bind oxygen. If 2CO bind, it pushes haemoglobin to its high affinity state and so altho oxygen binds it cannot be released to the tissues.
How does adult haemoglobin vary compared to fetal haemoglobin?
Adults and foetus must have different haemoglobin so that oxygen in transferred from mother to foetus. The foetal Haemoglobin therefore has a high affinity for oxygen than the maternal Haemoglobin.
What is the amino acid change in sickle cell anaemia? And why does this cause a problem?
Glutamate to Valine.
This is a hydrophilic residue changing to a hydrophobic residue. The hydrophobic residues stick together to exclude water and this means that chains are formed.
Why can’t sickle red blood cells pass easily through capillaries?
The chains of haemoglobin molecules bind to the cell membrane which makes the cell rigid and unable to squash.
What is thalassaemias?
Genetic disorders where there is an imbalance between a and B haemoglobin chain formation. This means that there will be too many of one type. a chains cannot form tetramers but precipitate and form polymers. B chains can form tetramers but these have increased oxygen affinity.
Where is myoglobin found?
In the muscles.
