Oxygen Transport Flashcards
What molecules can haemoglobin bind? (3)
Oxygen
Carbon dioxide
H+
Where is myoglobin present?
Skeletal and cardiac muscle
How many haem groups are found in a haemoglobin molecule?
How many oxygen molecules can a Hb molecule bind?
How many haem groups are found in a myoglobin molecule?
How many oxygen molecules can a myoglobin molecule bind?
4
4
1
1
What is the structure of a haem group?
Fe2+ bonded to 4 nitrogen atoms in the centre of the ring structure
2 additional bonds can be made, 1 bond is made to a histidine residue, the other to an oxygen molecule
What is the structure of myoglobin?
Single polypeptide chain
Mainly alpha-helical
How does oxygen bind to a haem group? What change does this result in?
Oxygen binds to Fe atom - which usually sits below the plane of the ring
Binding of the oxygen results in Fe atom moving into the plane of the ring —> small change in protein conformation
What type of curve does oxygen binding in myoglobin show?
Hyperbolic
What type of curve does haemoglobin binding to oxygen show?
Sigmoidal
What is p50?
The partial pressure at which there is 50% saturation of myoglobin/haemoglobin with oxygen
What is the structure of a haemoglobin molecule?
4 polypeptide chains - 2 alpha and 2 beta
4 haem groups - 4 oxygen molecules
Haemoglobin can exist in which two states?
T state - low affinity
R state - high affinity
What stabilises the structure of the T state?
Interactions between +ve histidine and -ve aspartate residues
Are Haem groups are more exposed in T or R state haemoglobin?
R state
How does binding of oxygen promote stabilisation of the R state?
Binding of oxygen pulls fe into the plane of the ring of a haem group resulting in a change in conformation of the Hb molecule - interactions lost due to small rotation and haem groups more exposed for binding
Why is the haemoglobin oxygen curve sigmoidal?
Due to cooperative binding of oxygen (cooperativity)
Binding affinity for oxygen increases as the number of oxygen molecules bound increases
What does the sigmoidal binding curve for Hb suggest about the states of haemoglobin in the blood?
There is a mixture of Hb in the high and low affinity states
What is the benefit of the sigmoidal curve of Hb for the body?
Allows haemoglobin to be more sensitive to small changes in [O2]
Loading/unloading of oxygen is more efficient
Shifting of an oxygen binding curve to the left _________ affinity
Increases
Shifting of an oxygen binding curve to the right _________ affinity
Decreases
What does the binding of 2,3-bisphosphoglycerate (BPG) result in?
Shifts oxygen binding curve to the right
Decreases affinity of Hb to oxygen
Increases efficiency of Hb as an O2 carrier
How does BPG bind to Hb?
1 molecule of BPG binds to one Hb molecule usually in the centre
What happens to [BPG] at high altitudes? Why?
Increased concentration. More oxygen is released at the tissues.
How does CO2 bind to Hb molecules?
Covalently bonds to n-terminus of each chain
How do H+ ions bind to Hb?
They protonate -ve amino acids
What effect does the binding of CO2 and H+ ions have on the affinity of Hb for oxygen?
Lowers the affinity
How does the Bohr effect help with the supply and demand of oxygen at metabolically active tissues?
At metabolically active tissues —> high [H+]
Lower affinity of Hb for oxygen —> oxygen released at respiring tissues
How does CO poisoning work?
Binds very tightly to Hb and with a higher affinity
Stopping oxygen transport
When is CO poisoning fatal?
When 50% or more of the Hb is CO bound
How does binding of CO to haemoglobin affect other subunits?
Increases affinity of unaffected subunits for oxygen
What is the structure of HbA and HbF?
HbA = adult haemoglobin (vast majority) - 2 alpha chains, 2 beta
HbF = fetal haemoglobin - 2 alpha, 2 gamma chains
What are features of HbF?
Has a higher affinity than HbA for oxygen - so oxygen passes from the mother to the foetus
Sickle cell anaemia is cause by a mutation in which gene?
Beta-goblin gene
How does the mutation of glutamate to valine in the beta globin gene in sickle cell anaemia, change the structure of the haemoglobin molecule?
Results in the formation of a hydrophobic ‘sticky’ pocket
How do sickle cell haemoglobin (HbS) interact with other Hb molecules?
Polymerises with other Hb molecules causing suckling of RBCs
Sickle RBCs are more prone to ______
Lysis
What are thalassaemias?
Group of genetic disorders resulting in incorrect proportions of alpha and beta globin chains
What is B-thalassaemia?
Decreased/absent b-globin chain production
What is a-thalassaemia?
Decreased/absent a-globin chain production
Is beta-thalassaemia developed before or after birth?
Onset after birth
Is alpha-thalassaemia developed before or after birth?
Before
Can B-globin chains form stable tetramers?
Yes, with increased affinity for oxygen
Can a-globin chains form stable tetramers?
No
