haemoglobin as an allosteric protein to transport oxygen Flashcards
What are the advantages of the shape of red blood cells?
Diffusion of oxygen and able to fit in capillaries
What is the structure of haem?
Haem is porphyrin and iron. The porphyrin is a tetrapyrolle. There is a hydrophobic end and a hydrophilic end.
What causes brown blood?
Redox state of the iron - Fe3+ is oxidised and gives dark brown blood - Met Hb
What causes blue blood?
Cyanosis - cyanide binding instead of oxygen
What causes cherry red blood?
Carbon monoxide binding instead of oxygen
What causes dark red blood?
deoxyhaemoglobin
What causes red blood?
oxyhaemoglobin
What is the secondary structure of haemoglobin?
alpha helix
What is the quaternary structure of haemoglobin?
tetramer
What is myoglobin?
Myoglobin is found in the muscle and it stores oxygen - its structure is the same as the tertiary structure of haemoglobin
What is the structure of myoglobin?
8 right handed alpha helices labelled A to H, hydrophilic on outside and hydrophobic on the inside which makes it very soluble
Where does oxygen in the tissues go?
Either to myoglobin or to mitochondria
What is the structure of haemoglobin in adults?
Two alpha subunits and two beta subunits
What is the structure of foetal haemoglobin?
Two alpha subunits and two gamma subunits
Where does the globin coordinate with the iron?
At the nitrogen on histamine residues E7 and F8 - F8 constantly locks on but E7 can be displaced by oxygen
What is the difference between the oxygenated and deoxygenated structures of haemoglobin
In the oxygenated state the iron is in the haem plane. In the deoxygenated state iron is pulled out of the haem plane towards F8. The oxygenated state is the relaxed (R) state and the deoxygenated state is the tense (T) state
Why is the deoxy-Hb form more rigid than the oxy-Hb form?
Because of the 8 salt bonds which are formed
What pathway makes BPG?
1,3-bisphosphoglycerate from the glycolysis pathway is converted to 2,3-bisphosphoglycerate by mutase
Where does BPG bind?
Binds to the deoxygenated Hb because BPG has 5 negative charges which fit in to a cavity between the beta subunits with 8 positive charges. It stabilises deoxy-Hb and prevents oxygen from rebinding in the tissues. It is dissociated when oxygen binds again in the lungs because they oxygen at a higher concentration can push its way in.
What shape is the oxygen saturation curve for haemoglobin?
sigmoidal
What shape is he oxygen saturation curve for myoglobin?
hyperbolic
What pO2 gives 50% saturation for haemoglobin?
26 Torr
What pO2 is in the tissues?
20-40 Torr
What pO2 is in the lungs?
100 Torr
In which direction does the oxygen saturation curve shift in acid?
To the right
What is the Bohr effect?
Where active tissue produces acid and stimulates haemoglobin to yield more oxygen in the active tissue
Why does the Bohr effect occur?
Because two histidine residues become positively charged in acid and lock deoxyHb more strongly
What does an oxygen saturation curve that has been shifted to the right mean?
That deoxyhaemoglobin is more stable and that oxygen is more likely given up in the tissues
What is subunit cooperativity?
Subunit cooperativity means when one oxygen binds it causes a conformational change in neighbouring haemoglobin allowing oxygen to more easily bind. The same happens when oxygen is released, when one leaves the rest foliow.
What happens to the oxygen saturation curve when effectors (CO2 and BPG) are no longer present?
Haemoglobin has properties more like myoglobin (hyperbolic curve)
Which has more affinity for oxygen, adult haemoglobin or foetal haemoglobin?
Foetal haemoglobin
Why does foetal haemoglobin need more affinity for oxygen?
Because it needs to be able to take the oxygen from the adult circulation in the mother
Why does foetal haemoglobin have more affinity for oxygen?
Because it binds BPG less strongly because there are only 6 instead of 8 negative charges in the cavity
What happens in altitude?
There is more BPG which shifts the curve to the right - this means that the P50 is raised from 26 to 31 Torr so more oxygen is delivered to the tissue
What is the cause of sickle cell anaemia?
A glutamic acid amino acid in haemoglobin is mutated to valine. The valine binds to a hydrophobic pocket in deoxy-haemoglobin to form insoluble crystalline structures.
What percentage of dry red blood cell is haemoglobin?
97%
