Oxygen transport 13 Flashcards
Where is haemoglobin found?
Erythrocytes in the blood
Where is myoglobin found?
Heart and skeletal muscle cells
Why does oxygen need to be transported via haemoglobin?
It is non-polar, not very soluble in water and stable, so it couldn’t be transported efficiently without it
What is the function of myoglobin?
It is a temporary store for oxygen, and transports oxygen from the erythrocytes to the mitochondria of muscle cells
What is haemoglobin called when it is bound to carbon dioxide?
Carbaminohaemoglobin
What is the structure of a haem group and how does oxygen bind to it?
A protoporphyrin ring with Fe at its centre, connected to 4 N atoms of the ring. This Fe can make 2 additional bonds to oxygen, one above and one below the ring
How does oxygen bind to the haem group in myoglobin and haemoglobin?
The Fe atom in the haem group is bound to the rest of the protein via a histidine residue on one side of the protoporphyrin ring, so the Fe can only form one bond with an oxygen molecule
What level of protein structure does myoglobin have?
Tertiary, as it is only made up of one subunit
What are some features of myoglobin structure?
It is a small protein, it is compact and globular, it is 75% α-helical (secondary structure)
Where is the Fe located in myoglobin?
His 93 in the 8th α-helix
How is Fe bound in myoglobin and haemoglobin?
Via covalent bonds to N atoms
What happens when oxygen binds to the haem in myoglobin and haemoglobin?
It causes the movement of Fe from slightly below the plane of the ring into the plane of the ring, causing movement of the histidine and a small change in overall protein conformation. This doesn’t have much effect in myoglobin but it does in haemoglobin.
What type of oxygen dissociation curve would a graph of oxygen saturation (y) vs partial pressure of oxygen (x) in myoglobin show? What about in haemoglobin?
Myoglobin - hyperbolic
Haemoglobin - sigmoidal
(1)
What is the quaternary structure of haemoglobin?
Formed of 4 polypeptide chains; two α and two β subunits. Each subunit has a haem group, and is very similar in conformation to myoglobin
What are the two states haemoglobin can exist in?
T state - low affinity for oxygen as haem groups are less exposed, there is larger lumen in centre of protein
R state - high affinity for oxygen as haem groups are more exposed, there is smaller lumen in centre of protein
What effect does oxygen binding to a haem group have in haemoglobin?
It promotes a conformational change, changing the protein from a T state to an R state and so increasing the affinity for oxygen of the other haem groups, resulting in a sigmoidal binding curve as the binding affinity changes with the curve
Why is the oxygen binding curve for haemoglobin sigmoidal?
Oxygen binds cooperatively, so its binding affinity increases as more oxygen molecules bind to Hb subunits, since the more oxygen are bound to the Hb the more exposed the other haem groups are
Can you explain this diagram? (2)
(3)
What effect does 2,3-bisphosphoglycerate (BPG) have on oxygen binding?
One BPG molecule binds per tetramer, and its negatively charged parts bind to the positive parts of haemoglobin, sitting in the ‘hole’ in the centre, making the haemoglobin less flexible and lowering its affinity for oxygen
How is oxygen binding of haemoglobin affected at high altitudes?
At high altitudes, BPG concentration increases, promoting oxygen release at tissues as they need more of it, so the BPG shifts the curve to the right to lower oxygen affinity
At what concentration is BPG usually present at in erythrocytes?
～5mM
Describe the BOHR effect
H+ and CO2 an both bind to haemoglobin, and when they do they lower its oxygen affinity. This is because when you exercise lactate (acidic) is produced, so your tissues need you to release more oxygen from the haemoglobin, therefore shifting the curve to the right as pH decreases
Why is CO so dangerous? How do you treat CO poisoning? At what percentage of COHb is it fatal?
It binds 250x more readily than oxygen, as it binds to the Hb
Put the patient in a hyperbaric chamber to increase pO2, so it competes with the bound CO
50%
Which haemoglobins are found in a normal adult?
HbA - ⍺2β2 - 90%
HbF - α2γ2 - <2%
HbA2 - α2δ2 - 5%
