Proteins in action 2 Flashcards
How does oxygen binding change the shape of haem and haemoglobin?
Deoxyhaemoglobin has a dished haem. In oxyhaemoglobin oxygen flattens the haem, and pulls histidine F8 and helix F toward the binding site. Anything that keeps helix F away will weaken oxygen binding
Oxygen changes haemoglobin shape
Compared to deoxyhaemoglobin, O2 binding to oxyhaemoglobin moves the Fe2+ into the plane of the haem, draws His F8 down and repositions helix F
Shifts in the orientation of protein secondary elements such as helix F moving relative to helix C are called conformational changes
What is BPG?
An allosteric inhibitor of O2 binding to haemoglobin
Positively charged allosteric site includes histidine and lysine side chains and the amino termini of the delta chains
How is Haemoglobin is under allosteric control of BPG?
BPG binds to deoxy-Hb by electrostatic interactions
BPG stabilises Hb in the deoxy T-state reducing oxygen affinity
BPG is produced during respiration in peripheral tissues so promotes oxygen release where needed
How does cooperativity allow efficient unloading?
Monomeric myoglobin has a hyperbolic binding curve
Cooperative, tetrameric haemoglobin has a sigmoidal binding curve
At arterial pressure both haem and myo are nearly 100% saturated but weak haem will dump less in lungs as in cooperative state
How is cooperativity prominent only in present of allosteric inhibitors?
Allosteric inhibitors BPG, CO2 and H+ stabilise the T-state. This unmasks cooperativity
In absence of inhibitors stripped haem is predominantly in R state so shows lack of cooperativity
How does CO2 reduce O2 affinity both directly and via lowered pH of blood?
Elevated CO2 and low pH in metabolising tissues both reduce the affinity of haemoglobin for O2 (Bohr effect)
CO2 can bind to the amino-terminal amino group stabilising deoxy-Hb conformation in T state
As pH rises, weaker binding because depronation of His side chains abolishes ionic interaction with negatively charged phosphates of BPG
Why is weaker binding sometimes better?
First substantial adaptation to high altitude is an increase in BPG. This reduces haemoglobin oxygen binding. Rightward shift of the binding curve delivers more oxygen to the tissues
Physiological effects of haemoglobin
Oxygen affinity is tuned in foetuses and at high altitude. Mutations to haemoglobin impair oxygen transport. Sickle-cell anaemia results from haemoglobin polymerisation
How do foetuses hold oxygen tighter?
Different amino acid sequences of normal Hb subunits alter their O2 binding properties. Higher affinities for O2 allowing foetus to capture O2 in placenta
Foetal Hb is less sensitive to BPG therefore binds oxygen more tightly
