Protein Function - Oxygen Transport Flashcards
What is the role of myoglobin?
Pick up O2 from haemoglobin
What is the structure of haem?
Protoporphyrin ring and an Fe atom bound to 4N atoms of the ring
Fe2+ can make 2 additional bonds to oxygen, one on either side of the plane
Describe oxygen binding to the haem group
1 molecule of O2 binds to the haem group in myoglobin and haemoglobin
Fe atom is bound to the protein via a histidine residue on other side of ring
Name features of myoglobin structure
Globular 153 aa Compact 75% alpha-helical One polypeptide chain
What shape curve represents the binding of oxygen by myoglobin?
Hyperbolic
Rapid increase at first and quickly plateaus
What shape is the oxygen dissociation curve for haemoglobin?
Sigmoidal
Affinity not constant
What are the features of haemoglobin structure?
2 polypeptide chains in alpha2beta2 tetramer
Each chain contains essential haem prosthetic group
Conformation of each chain very similar to myoglobin
What are the 2 states deoxyhaemoglobin can exist in?
Low affinity T state
High affinity R state
How is the R state promoted?
Oxygen binding promotes stabilisation of the R state
Promotes more oxygen binding so haemoglobin has a higher affinity for oxygen
What is cooperative binding?
Binding of one oxygen molecule promotes the binding of subsequent molecules
This means it is more sensitive to small differences in O2 concentrations
Why would the T state alone not be beneficial?
Oxygen does not bind well as it has a low affinity
It therefore can’t carry much O2
Why would the R state alone not be beneficial?
Oxygen binds tightly so the haemoglobin would not easily give up the oxygen
What is the purpose of 2,3-bisphosphoglycerate (BPG)?
It lowers the affinity for O2 in haemoglobin
Present in RBC at ~5mM
1 BPG binds per haemoglobin tetramer
BPG concentration increases at high altitudes, promoting O2 release at the tissues
What is the Bohr effect?
Binding of H+ and CO2 lowers affinity of haemoglobin for oxygen
It ensures the delivery of oxygen is coupled to demand
Why is the Bohr effect not exhibited in myoglobin?
Myoglobin only consists of a single polypeptide chain
Describe what happens in carbon monoxide poisoning and how to treat it
It combines very tightly with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport
CO binds to haemoglobin more readily than oxygen
Treat with blood transfusion or a hyperbaric chambers
What are the 3 normal adult haemoglobins?
HbA alpha2beta2 (90%) HbF alpha2gamma2 HbA2 alpha2delta2
What is the major haemoglobin in fetal blood and how is it different?
HbF
Higher binding affinity for oxygen than HbA (maternal blood), allows transfer of oxygen to fetal blood supply from mother
What occurs in sickle cell anaemia?
Mutation of glutamate (hydrophilic) to valine (hydrophobic) in beta globin (missense mutation)
Haemoglobin molecules combine to bury hydrophobic valines
Long chains of haemoglobin forms (sickled cells)
These cells more prone to lyse
What are thalassaemias?
Group of genetic disorders where there is an imbalance between number of alpha and beta globin chains
