Medical Cell Biology and Genetics - Hb and Myoglobin Flashcards
What is myoglobin?
A protein in the skeletal muscle that acts as a store of oxygen.
Contains 1 haem group so can 1 bind one molecule of oxygen
What is haemoglobin?
A tetrameric protein - 2 alpha 2 beta subunits, that transports oxygen in the systemic circulation
Has 4 heam groups so can bind 4 molecules of oxygen
Why is haemoglobin a more appropriate oxygen transporter than myoglobin?
Haemaglobin exhibits sigmoidal oxygen binding therefore exists in 2 states:
- High affinity R state
- Low affinity T state
Therefore when pO2 is high (eg at lungs) Hb will bind oxygen and when pO2 is low (eg at tissues) Hb will dissociate oxygen.
Myoglobin however shows hyperbolic oxygen binding therefore has a very high affinity for oxygen - so wont release it at the tissues.
What is the effect of 2,3-BPG on haemoglobin and why is this useful?
2,3-BPG decreases the affinity of Hb for O2 so shifts the dissociation curve to the right.
This is useful because more 2,3-BPG is produced at high altitudes therefore promoting oxygen release at the tissues.
2,3-BPG is also produced during metabolism promoting O2 release at v metabolically active tissues.
What is the effect of CO2, CO and H+ on haemoglobin?
CO2 and H+ decrease the affinity of Hb for O2 therefore shifts curve to the right. Produced at metabolically active tissues - know as the Bohr shift.
However CO binds to Hb 250x more readily than O2 therefore is COHb >50% this is fatal.
What is the cause of sickle cell disease?
A single nucleotide polymorphism resulting in change of hphilic glutamate —> hphobic Valine in the beta subunit of Hb.
What causes a sickle cell crisis?
Val forms a ‘sticky hydrophobic pocket’ allowing deoxygenated Hb to polymerise (straight chain). This distorts RBC and makes them sickle shaped.
They are unable to fir though capillaries and therefore block vasculature - tissues become ischaemic which causes a vast amount of pain.
NB The stress to the cell membrane from the distortion causes premature cell lysis therefore SDC can cause anaemia.
What are thalassaemias?
Genetic blood disorders where there in an imbalance between alpha and beta subunits resulting in abnormal Hb.
What are the main features of alpha and beta thalassaemias
Alpha thalassaemias:
- decreased or absent alpha chains
- the excess beta chains for stable tetramers with an increased affinity for oxygen
- onset before birth
Beta thalassaemias:
- decreased or absent beta chains
- alpha chains unable to form stable tetramers
- onset after birth
