Myoglobin and haemoglobin Flashcards
1
Q
2 models of O2 binding to Hb
A
sequential and concerted
2
Q
function of myoglobin
A
oxygen store in muscle
3
Q
function of haemoglobin
A
oxygen transporter in blood
4
Q
haem group structure
A
- 4 pyrrole rings linked together (a protoporphyrin) in a planar structure
- Fe is constrained in the ferrous form Fe2+ (prevents Fe oxidising to Fe3+)
- Fe must be in the ferrous Fe2+ form to enable binding of oxygen
- Fe has six coordinate bonds - four to the haem, one to the globin and one to the O2
- Binding of oxygen to the Fe2+ is a reversible interaction
5
Q
myoglobin structure
A
- Single protein molecule (monomer)
- Protein primary structure - 150 amino acids proteins
- Secondary structure - eight alpha-helices A-H
- Almost no beta sheets
- Protein fold - hydrophobic pocke
6
Q
haem binding to myoglobin
A
- Haem binds to histidine in helix F, position 8 (F8) in globin protein
- A globin protein evolved with a hydrophobic pocket (many hydrophobic side chains)in which a haem group could bind (globin + haem = myoglobin)
7
Q
what does His E7 in haem group do
A
- distorts binding of gas molecules to 6th co-ordination position on Fe
- The position of His E7 sterically hinders and reduces the binding affinity of oxygen (and also the respiratory poison carbon monoxide, CO, to which Mb binds much more readily than oxygen) to myoglobin
8
Q
myoglobin vs haemoglobin O2 binding and release
A
- Myoglobin is O2 saturated at low pO2
- O2 only released to muscle cells when cellular pO2 is very low
- Hence myoglobin has evolved to function as a “backup” store of O2 in muscle cells
- Haemoglobin functioning as an O2 transporter in blood had to evolve a much weaker binding affinity for oxygen - binds at high pO2 and releases at low pO2
9
Q
haemoglobin O2 binding and release
A
Haemoglobin has had to evolve binding O2 less tightly because O2 must be released in peripheral tissues where myoglobin does not release it
10
Q
how many oxygen molecules and atoms can bind to Hb
A
4 O2 molecules, 8 O atoms
11
Q
Hb subunits
A
2 alpha and 2 beta globins
12
Q
Hb binding of oxygen effect
A
- Tetramer globin subunits interact (cooperate) with each other
- Results in binding or releasing O2 progressively more easily as each subunit influences neighbouring subunits
- Results in sigmoidal O2 saturation curve (binding one O2 makes it easier to bind the 2nd and the 3rd O2 etc)
13
Q
cooperative binding of oxygen to Hb
A
- Binding of O2 to one subunit of Hb tetramer induces conformational change in the subunit
- Conformational change in transmitted to adjacent subunits which are in contact, making binding of O2 to these subunits easier
14
Q
conformational change in Hb when O2 binds
A
- When O2 binds to deoxy-Hb, the Fe2+ moves into the plane of the haem ring and draws the His F8 down, leading to repositioning of the F helix
- This results in conformation change in each Hb subunit on binding to oxygen, as movement of the F helix causes a change in conformation in the rest of the protein
15
Q
effect of BPG on O2 release
A
- 2,3-biphosphoglycerate (BPG) fits into the bigger central cavity in deoxy-Hb and bind
- This holds Hb in the deoxy conformation ensuring O2 releases to cells and does not re-bind to Hb
- This effect contributes to the release of oxygen from haemoglobin at peripheral tissues where the local pO2 is relatively low and oxygen is being taken up by cells to enable aerobic metabolism
- The relatively high pO2 at lungs displaces BPG when binding of O2 to deoxy-haemoglobin occurs
