Lec 14 - Protein Function - Oxygen Transport Flashcards
what is myoglobin ?
a single haem unit - can bing one O2 molecule
briefly outline how O2 transport works in the body
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
How does O2 bind to myoglobin ?
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
How does O2 bind to haemoglobin ?
relates this to strucutre
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
what is the benefit of the sigmodial shape curve ?
draw curves if you can
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
why is cooperativity useful ?
this is know as the co-operative binding of O2 - allows for greatest amount of O2 release
what is the role of 2,3 - bisphosphoglycerate (2,3 - BPG) in O2 binding to haemoglobin ?
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
What are the roles of CO2 and H+ in O2 binding?
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
explain carbon monoxide poisoning in terms of its affect on O2 affinity
combines with ferrohaem/myo globin
blocks O2 transport
CO binds far more easily to haemoglobin than O2
fatal when COHB is over 50%
how are globulin gene organised in an adult ?
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
why is fetal haemaglobin important ?
draw graphs to demonstrate
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
how does sickle cell anemia work ?
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
what is a thalassaemia ?
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
what are the allosteric affectors for haemaglobin
draw if you can
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
