Hemoglobin and Sickle Cell info Flashcards
myoglobin structure and location
single polypeptide chain with tertiary structure, mainly alpha helices…high affinity for 1 molecule of oxygen
in muscle cells
hemoglobin A structure
4 polypeptide chains, 2 alpha and 2 beta chains each can bind an oxygen
A1B1 and A2B2 bind together well
hemoglobin F structure
2 alpha chains and 2 gamma chains, fetal Hb
hemoglobin A2 structure
2 alpha and 2 delta chains, low percent in adults
what chromosomes are alpha chains and beta like chains on?
alpha is on chromosome 16 and beta like are all on 11
pyrrole rings in heme function
interact with surrounding alpha and beta chains to stabilize heme binding
6 coordination sites of iron and what are they bound to?
4 are bound to Ns in the pyrrole rings, one in front for binds oxygen and one in back for stability
shape of myoglobin binding curve?
hyperbolic
shape of hemoglobin binding curve?
sigmoidal because affinity increases with binding
what happens when oxygen binds the heme molecule?
the proximal and distal histidines cause attached alpha helices to move resulting in conformational change in the at interface of the alpha beta dimer in Hb molecule
What does 2,3-DPG do to Hb?
causes Hb to favor the taut deoxygenated form leading to more oxygen release
it does not bind fetal Hb as well as adult Hb
Haldane effect definition
in lungs high PO2 drives O2 onto Hb releasing H+ and leads to formation of CO2 and H2O
Bohr effect definition
more acidic body tissue so H+ binds RBCs and forces O2 off the molecule
4 competitors of oxygen for binding with Hb?
carbon monoxide, cyanide, nitrogen dioxide, and hydrogen sulfide
carboxyhemoglobin
carbon monoxide bound to heme
methemeglobinemia cause and presentation
due to 3 amino acid change on distal side of heme
leads to Fe3+ instead of Fe2+
cyanosis and brown blood
most common cuase of methemeglobinemia?
mutations in pentose phosphate pathway especially G6PD deficiency
cytochrome b5 reductase role in methemeglobinemia
helps reduce Fe3 to Fe2 so without it then you are stuck with met Hb
What is the sickle cell mutation?
on the BETA CHAIN changes glutamine 6 into valine 6…valine is much more hydrophobic and does not have a negative charge like glutamic acid
what form of HbS can participate in sickling?
only the deoxy taut form
what is a common cause of worsening sickling in individuals with sickle cell anemia?
dehydration causes the cells to clump easier and leads to more sickling
what is effect of vasoconstriction or partial occlusion on sickling?
more likely to sickle because the deoxygenated blood may spend more time deoxygenated
what is the shape of a deoxygenated sickling curve?
sigmoidal due to exponential increase once you have nucleus of sickling
what is the shape of the unsickling curve? and why?
this is a linear graph…because you dont have that nucleus of sickling starting exponential unsickling…they just slowly unsickle with increasing po2
what is the delay time in sickling and why is it important for patients with sickle cell?
delay time is the amount of time spent in po2 of zero before the sickling event starts…this is important because cells often do not spend enough time in the po2 of zero area to allow the nucelarization of the sickling to begin
Does an acidic environment increase or decrease sickling? how?
increases because of the presence of H+ helping favor the deoxy state of Hb
