Lecture 12 Flashcards
In which state is the haem dished?
Deoxygenated state
What occurs when haemoglobin becomes oxygenated?
The oxygen flattens the haem, and pulls histidine F8 and helix F towards the binding site
What weakens the oxygen binding to the haem?
Any other bond that pulls alpha helix F away
What are conformational changes
Shifts in the orientation of a proteins secondary elements
What can confirmational changes cause in haemoglobin?
The balance of T <-> R states
What are the ways in which conformational changes can occur in haemoglobin?
Allosteric regulation, pH, physiological / genetic changes
What are allosteric inhibitors
Compounds which can bind and stabilise the T-state, unmasking cooperativity
What are examples of allosteric inhibitors?
BPG, CO2, H+
What is stripped haemoglobin?
Haemoglobin which has no allosteric inhibitors
What state is stripped haemoglobin in?
R-state, showing little cooperativity
What occurs in haemoglobin in the absence of allosteric inhibitors?
The O2 binds too tight, increasing O2 affinity and making it hard to remove
What is BPG?
An allosteric inhibitor that stabilised Hb in the deoxy T-state reducing oxygen affinity
How does BPG bind to deoxy-Hb?
Through electrostatic interactions
When is BPG produced?
During respiration in peripheral tissues to promote oxygen release
What is the Bohr effect?
The reduction in affinity of haemoglobin for O2 in metabolising tissues with elevated CO2 and H+ leading to low pH
What are the two components of the Bohr effect?
Lower pH favours the protenation of histidine residues and promotes stronger interactions in the T-state.
CO2 can bind to the animo-terminal amino group, stabilising deoxy-Hb conformation in the T state
What is true if the Hb curve is more sigmodial?
The pH is lower
What are the forms of foetal haemoglobin?
Beta, gamma and alpha
What are the general forms of foetal haemoglobin?
2x alpha and 2x gamma
What are the general forms of post-natal haemoglobin
2x alpha and 2x beta
What is the difference between foetal and post-natal Hb oxygen affinity?
Foetal haemoglobin is less sensitive to BPG so, therefore, binds oxygen more tightly
What is the difference between the beta and gamma chains in haemoglobin?
The gamma chain has serine residues replacing two of the His residues at the BPG binding site
What is HbS
Sickle cell haemoglobin
What is the mutation in HbS?
Hb beta E6V variant
