Lec 14 - Protein Function - Oxygen Transport

a single haem unit - can bing one O2 molecule

LUNGS - high O2 conc O2 binds to Haemoglobin tavels in blood as oxyhaemoglobin to tissue TISSUE - Low O2 conc haemoglobin releases O2 CO2 binds to Haemoglobin carboxyhaemoglobin travels to the lungs CO2 is released myoglobin in tissues can act as a temporary store of O2 for each haem goup ( 4 in haemoglobin ,1 in myoglobin) one molecule of O2 can bind

hyperbolic curve (draw shape) means O2 affinty is very high , so binds in low concs binding of O2 causes a structural change - Fe moves into plane of ring structure - slight change in protein confirmation

forms a sigmoidal curve made of 4 polypeptide grouos 2 aplha haem groups and 2 beta haem groups form a tetramer deoxyhaemaglobin can exist as low affinty T state and high affinty R state - heam groups are more exposed - O2 acces better each new oxygen that binds promotes a change in haemoglobin confirmation stabilisation of the high affinity R state - therefore O2 affinty increases with each O2 that binds - leads to sigmodial curve this is know as the co-operative binding of O2 - allows for greatest amount of O2 release 1st binding of O2 is hard - low affinty last binding is easy - high affinty

it means that O2 is picked up very easy in lungs - high affinty state at high O2 concs in low affinty T state in tissues where O2 conc is low O2 is released easily allows for efficient carrying of O2 from lungs to tissues

this is know as the co-operative binding of O2 - allows for greatest amount of O2 release

used in regulation lowers the O2 binding affinty - so O2 can be release to greater effect in tissues always present in RBC at 5mM 1 2,3-BPG binds per haemoglobin tetramer - negatively charged and will reduce heam group exposure as positive charges pushed away this stabilises the Low affinty T state we have more BPG at high altitudes - helps with O2 release into tissues

H+ and CO2 can bind to haemoglobin molecules if they bind they lower affinty of haemoglobin for O2 - the BHOR effect metabolically active tissues produce lots of CO2 and H+ - reduce O2 affinty - so more O2 can be released into cells that need it more - O2 is coupled to demand

combines with ferrohaem/myo globin blocks O2 transport CO binds far more easily to haemoglobin than O2 fatal when COHB is over 50%

main adult haemaglobin is HbA can be glycosylated to HbA1c some exists as HbA2 we also have fetal HbF as a fetus as we develop from fetus to child to adult the expression of different globulin genes is regulated / changed

HbF has a higher binding affinity for O2 so allows O2 transfer between mums HbA and the fetus HbF the curve is more like myoglbin - hybobolic curve

mutation of glutamine to valine in B unit globulin so now HbS valine is sticky an hydrophobic, the deoxygenated HbS will aggregate / polymerise this aggregation can make cells lyse (burst) - cells are sickle shapes

a genetic disorder where there is an imbalance between the alpha and beta globulins. B thalassaemia - decreased or no beta globulin alpha chains cant form stable tetramers patient less effect at carrying O2 A thalassaemia - decrease or no alpha globulin varies in severity B chains form stable tetramers - with an increased affinty for O2 - wont give up O2 as easily

allosteric acivator shifts the curve to the left - enhance high affinity R state allosteric inhibitor - shift the curve to the right - enhance low affinity T state CO2 , H+, 2,3 BPG are allosteric affectors