Hemoglobin and Sickle Cell info

Question 1

myoglobin structure and location

Answer 1

single polypeptide chain with tertiary structure, mainly alpha helices…high affinity for 1 molecule of oxygen

in muscle cells

Question 2

hemoglobin A structure

Answer 2

4 polypeptide chains, 2 alpha and 2 beta chains each can bind an oxygen

A1B1 and A2B2 bind together well

Question 3

hemoglobin F structure

Answer 3

2 alpha chains and 2 gamma chains, fetal Hb

Question 4

hemoglobin A2 structure

Answer 4

2 alpha and 2 delta chains, low percent in adults

Question 5

what chromosomes are alpha chains and beta like chains on?

Answer 5

alpha is on chromosome 16 and beta like are all on 11

Question 6

pyrrole rings in heme function

Answer 6

interact with surrounding alpha and beta chains to stabilize heme binding

Question 7

6 coordination sites of iron and what are they bound to?

Answer 7

4 are bound to Ns in the pyrrole rings, one in front for binds oxygen and one in back for stability

Question 8

shape of myoglobin binding curve?

Answer 8

hyperbolic

Question 9

shape of hemoglobin binding curve?

Answer 9

sigmoidal because affinity increases with binding

Question 10

what happens when oxygen binds the heme molecule?

Answer 10

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

Question 11

What does 2,3-DPG do to Hb?

Answer 11

causes Hb to favor the taut deoxygenated form leading to more oxygen release

it does not bind fetal Hb as well as adult Hb

Question 12

Haldane effect definition

Answer 12

in lungs high PO2 drives O2 onto Hb releasing H+ and leads to formation of CO2 and H2O

Question 13

Bohr effect definition

Answer 13

more acidic body tissue so H+ binds RBCs and forces O2 off the molecule

Question 14

4 competitors of oxygen for binding with Hb?

Answer 14

carbon monoxide, cyanide, nitrogen dioxide, and hydrogen sulfide

Question 15

carboxyhemoglobin

Answer 15

carbon monoxide bound to heme

Question 16

methemeglobinemia cause and presentation

Answer 16

due to 3 amino acid change on distal side of heme

leads to Fe3+ instead of Fe2+

cyanosis and brown blood

Question 17

most common cuase of methemeglobinemia?

Answer 17

mutations in pentose phosphate pathway especially G6PD deficiency

Question 18

cytochrome b5 reductase role in methemeglobinemia

Answer 18

helps reduce Fe3 to Fe2 so without it then you are stuck with met Hb

Question 19

What is the sickle cell mutation?

Answer 19

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

Question 20

what form of HbS can participate in sickling?

Answer 20

only the deoxy taut form

Question 21

what is a common cause of worsening sickling in individuals with sickle cell anemia?

Answer 21

dehydration causes the cells to clump easier and leads to more sickling

Question 22

what is effect of vasoconstriction or partial occlusion on sickling?

Answer 22

more likely to sickle because the deoxygenated blood may spend more time deoxygenated

Question 23

what is the shape of a deoxygenated sickling curve?

Answer 23

sigmoidal due to exponential increase once you have nucleus of sickling

Question 24

what is the shape of the unsickling curve? and why?

Answer 24

this is a linear graph…because you dont have that nucleus of sickling starting exponential unsickling…they just slowly unsickle with increasing po2

Question 25

what is the delay time in sickling and why is it important for patients with sickle cell?

Answer 25

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

Question 26

Does an acidic environment increase or decrease sickling? how?

Answer 26

increases because of the presence of H+ helping favor the deoxy state of Hb