S14 Protein Function - Oxygen Transport Flashcards
Why is the structure of haem as it is?
To allow oxygen to bind
How is the Fe atom bound to Hb?
Bound via a histidine residue on the side of the ring
Is myoglobin large or small?
Small (153 amino acids (100 or more classes as a protein))
What does binding of oxygen mean happens to the plane in myoglobin?
Oxygen binding causes movement of Fe into the plane of the ring (causes a small change in protein conformation that has no major effects)
What type of curve is seen with oxygen binding to myoglobin?
Hyperbolic
What type of curve is seen with oxygen binding to Hb?
Sigmoidal
How many polypeptide chains is Hb made up of?
What about myoglobin?
2
1
What are the two states of Hb?
T - low affinity state
R - high affinity state
Which state does oxygen binding promote the stabilisation of?
The R state
What does binding of 2,3-BPG do to Hb?
Decreases Hb affinity of oxygen
BPG conc increases at high altitudes, promotes oxygen release at the tissues
What does binding of carbon dioxide and H+ do to Hb affinity for oxygen? What is its significance?
Lower the affinity (Bohr effect)
H+ and CO2 produced by metabolically active tissues - the Bohr affect means that delivery of O2 is coupled with demand
What is the affect of carbon monoxide poisoning on Hb?
Binds to the Fe in Hb (ferroHb) and blocks oxygen transport as CO can bind more readily than O2
What are the polypeptide chains in HbA, HbF and HBA2?
HbA - alpha 2 and beta 2
HbF - alpha 2 and gamma 2
HbA2 - alpha 2 and delta 2
What is the most common Hb in human adults?
HbA (90%)
What is the importance of foetal Hb (HbF)?
It is the major Hb in foetal blood
It has a higher binding affinity for oxygen than HbA which allows transfer of oxygen to the foetal blood supply from the mother
Which direction does the curve shift for increased affinity?
To the left
What mutation causes sickle cell anaemia?
Mutation of glutamate to valine in the beta globin (HbS)
What does the mutation Glu —> Val cause in Hb?
A sticky hydrophobic pocket (Val is hydrophobic, Glu isn’t) which allows HbS to polymerise.
What are sickled cells prone to? What is their structure?
More prone to lyse
More rigid (block microvasculature e.g. capillaries)
What are thalassaemias?
A group of genetic disorders where there is an imbalance between the number of alpha and beta globin chains
What is beta-thalassaemia? What form of Hb takes over?
- decreased/absent beta-globin chain production
- alpha chains unable to form stable tetramers
- symptoms appear after birth
(Major is both beta globins missing, minor is only one missing)
HbF takes over (not ideal in high amounts)
What is alpha-thalassaemia?
- decreased or absent alpha globin chain production
- different levels of severity due to multiple copies of the alpha chains present (alpha 1 and alpha 2)
- beta chains can form stable tetramers with increased affinity for oxygen
- onset before birth
What are the different levels of severity for alpha thalassaemia?
- Normal - 2 alpha-1, 2 alpha-2
- Silent carrier - 1 alpha-1, 2 alpha-2
- Alpha-thalassaemia trait (heterozygous clinically mild) - no alpha-1, 2 alpha-2
- Alpha-thalassaemia trait (heterozygous clinically mild) - 1 alpha-1, 1 alpha-2
- HbH disease (clinically severe) - 1 alpha-2
- Hydrops fetalis (fatal after birth) - none
How many haem subunits make up HbA?
4 haem containing subunits - 2 alpha, 2 beta
