Protein Function - Oxygen Transport Flashcards
What part of the haemoglobin does oxygen bind to?
An Fe2+ iron ion in the middle of a haem group.
What does haem groups consist of?
A protoporphyrin ring and an Fe2+ that is bound to 4 nitrogen atoms in the ring.
How is the Fe2+ bound to the haemgroup/protein?
Via a histidine residue (proximal histidine) on the other side of the ring.
What are the features of a myoglobin structure?
It is a globular tertiary structure. It is 153 aa long and compact. It is 75% alpha helical, no beta-pleated sheets and His 93 in the 8th alpha helix is covalently linked to Fe.
It is not a quaternary structure.
What is deoxymyoglobin?
A myoglobin molecules not bound to oxygen.
Where does the Fe sit in the deoxymyoglobin in relation to the plane of the protoporhyrin ring?
Slightly below the plane.
How does the Fe move as oxygen binds to it?
There is a small shift upwards so Fe sits in the middle of the plane of the ring. This is a small change in the overall protein conformation.
Describe the curve of how haemoglobin bind to oxygen.
It is sigmoidal.
How does the curve of myoglobin and haemoglobin differ and explain what this means.
Myoglobin is up-side-down L-shaped. Haemoglobin is sigmoidal. This means that myoglobin and haemoglobin binds oxygen differently. It also means that myoglobin has a higher affinity for oxygen than haemoglobin.
Outline the features of a haemoglobin molecule.
4 polypeptide chains. Two alpha polypeptides and two beta polypeptides in a a2b2 tetramer. These alpha and beta structure are called subunits and are globular proteins bound together non-covalently
Each chain contains an essential haem prosthetic group.
It has a quaternary structure and each subunit is fairly similar to a myoglobin molecule. This also means that there are 4 haem groups and 4 oxygen molecules can bind to one haemoglobin.
What are the two states of haemoglobin? How do they differ?
T state: a low affinity where the subunits are closer together as well as the polypeptide chains internally.
R state: a high affinity where the structure is a little bit more open so oxygen can bind more easily.
Which state does oxygen binding promote stabilisation for?
The R state with higher affinity.
Why is the oxygen binding curve for haemoglobin sigmoidal?
Oxygen makes a conformational change to the haemoglobin. This means that the more oxygen that bings to the Hb subunits the higher affinity for oxygen. This means that there is a promotion in the R state.
To clarify this means that binding the first oxygen molecule to the first subunits is hard as it has low affinity.
However the last oxygen molecule to the 4th subunit is easy because of its high affinity at that point.
What does cooperative binding of oxygen to haemoglobin mean?
That the more oxygen that binds the higher affinity for subsequent molecules.
Why is the sigmoidal curve of oxygen binding to haemoglobin important?
Because it means that oxygen can be efficiently carried from the lungs to the tissues.
It also mean that it is more sensitive to a small difference in oxygen concentration.
What is the formula for the sigmoidal curve of oxygen binding to haemoglobin? Explain what it means.
Y = pO2 / (pO2 + p50) Y = percentage saturation with oxygen as a fraction pO2 = partial pressure of oxygen (concentration) p50 = partial pressure giving 50% of the saturation
What other measurement in MCBG is p50 similar to?
Mikaelis Constant (Km)
What does an increase in p50 mean?
That there is a shift of the curve to the right. This means that the partial pressure of oxygen has to be higher in order to maintain 50% of oxygen saturation. This means that there is a lower affinity for oxygen to bind. This also means the haemoglobin is more prone to release oxygen.
What does a decrease in p50 mean?
That there is a shift of the curve to the left. This means that the partial pressure of oxygen will be lower in order to maintain a 50% of oxygen saturation. This means a higher affinity for oxygen to bind.
What part of the curve is found in tissues such as muscles and placenta?
The steep curve where the affinity is low.
What part of the is found in lungs?
The plateau where the affinity is high.
Give 4 factors that will regulate the p50.
pH (a low pH means less affinity) muscles pH is lower due to lactic acid e.g. The harder a tissue works the more acidic.
Temperature (high temperature means less affinity) also found in muscles.
pCO2 (an increase in pCO2 means less affinity for oxygen)
BPG (2,3 - Biphospoglycerate) Haemoglobin with 2,3 BPG has an increased p50 which results in lower affinity.
Where can you find an increased p50?
Muscles and placenta
Where can you find a decreased p50?
Lungs
