Oxygen Transport Flashcards
Why does oxygen need to bind to specific transporters?
Not soluble in water
Where is myoglobin found?
Muscle tissue
What does Haem consist of?
A protoporphyrin ring and an Fe atom bound to a N atoms of the ring
What does oxygen bind to and why?
Haem groups - Fe2+ can make 2 additional bonds to oxygen, one on either side of the plane
What is the Fe atom bound to the protein via?
Histidine residue on the other side of the ring
What are some features of the structure of myoglobin?
153 amino acids, compact, 75% alpha helical, His 93 in the 8th alpha helix is covalently linked to Fe
Where is Fe in deoxymyoglobin?
Slightly below plane of the ring
What does oxygen binding do to the Fe in myoglobin?
Moves Fe into plane of the ring which causes movement of His F8 and small change in overall protein conformation
What graph does oxygen binding to myoglobin show?
Hyperbolic dependence on oxygen concentration
In the graph of the binding of oxygen to myoglobin, what does Y, pO2 and P50 mean?
Y = percentage saturation with oxygen PO2 = partial pressure of oxygen P50 = partial pressure giving 50% saturation
What is the shape of the oxygen dissociation curve for myoglobin?
Rectangular hyperbola - due to being only one subunit
What is the shape of the oxygen dissociation curve for haemoglobin?
Sigmoidal - a consequence of the four subunits co-operating
What are some features of haemoglobin structure?
2 polypeptide chains - each containing haem prosethetic group
alpha chain (141 amino acids) and beta chain (146 amino acids) in a a2b2 tetramemer
In what two states can deoxyhaemoglobin exist in?
Low affinity T state (tense) ad high affinity R state (relaxed)
Which state of deoxyhaemoglobin does oxygen binding promote the stabilisation of?
R state
What does oxygen binding to haemoglobin cause?
Change in conformation
What is meant by the co-operative binding of oxygen?
Binding affinity for oxygen increases as more oxygen molecules bind to Hb subunits. Binding of the first oxygen molecule is hard as it has a low affinity but it gets progressively easier so that the binding of the last oxygen molecule to the 4th subunit is very easy - has a high affinity.
What does the sigmoidal binding curve of haemoglobin mean?
That oxygen can be efficiently carried from lungs to tissues and there is more sensitivity to small differences in oxygen concentrations
What effect does 2,3-Bisphosphoglycerate (BPG) have on oxygen binding?
Stabilises T state of haemoglobin so lowers the affinity making it harder for oxygen to bind
What is 2,3-BPG present in red blood cells at?
~5mM
What happens to the concentration of BPG at high altitudes?
Concentration increases to promote oxygen release at the tissues
What can regulate oxygen binding?
Binding of BPG, H+ and CO2
What does the binding of H+ and CO2 do to the affinity of haemoglobin for oxygen?
Decreases affinity
What does the Bohr effect ensure?
Ensures the delivery of O2 to tissues is coupled to demand. Metabolically active tissues produce large amounts of H+ and CO2.
Why is carbon monoxide poisonous?
CO combines with ferromyoglobin and ferrohaemoglobin, blocking oxygen transport. It also increases the affinity for oxygen for unaffected subunits
How much more readily does CO bind to haemoglobin than O2?
250x more readily
When is COHb fatal?
> 50%
What is the importance of faetal haemoglobin?
Has a higher binding affinity for oxygen than adult haemoglobin which allows transfer of oxygen to foetal blood supply from the mother
What is the mutation involved in Sickle Cell Anaemia?
Mutation of Glutamate to Valine in beta globin forming a ‘sticky’ hydrophobic pocket which allows deoxygenated HbS to polymerize.
What are sickle cells more prone to?
More prone to lyse - anaemia
Also more rigid - microvasculature
What are thalassaemias?
A group of genetic disorders where there is an imbalance between the number of alpha and beta globin chains.
What are beta-thalassaemias?
Decreased or absent beta globin chain prdouction meaning that alpha chains are unable to form stable tetramers.
Do symptoms of beta-thalassaemias appear before or after birth?
After birth
What are alpha-thalassaemias?
Decreased or absent alpha-globin chain production. Beta chais can form stable tetramers with increased affinity for oxygen. There can be different levels of severity as there are multiple copies of the alpha chains present.
Is alpha-thalassaemia onset before or after birth?
Before birth
