Lecture 11: Hemoglobin

Question 1

What increases the function of hemoglobin?

Answer 1

2-3 BPG, H+, and HbF

Question 2

List the global chains that are beta-like chains

AND what chromosome are they found on?

Answer 2

epsilon
gamma
delta
beta

Chromosome 11

Question 3

Describe alpha thalassemias

Answer 3

both alpha genes; depletion of 1,2,3,4

affects the production of fetal and adult Hb

Question 4

Describe the levels of 2,3 BPG in the lungs and in the active tissues

Answer 4

lungs has a low 2,3 BPG so that there is a high affinity for oxygen (leads to R form) so that the Hb takes up oxygen

tissues have a high level of 2,3 BPG which results in the T form, and makes the Hb release the O2 into the tissues

Question 5

List and describe the 4 classic types of alpha-thalassemias

Answer 5

1. alpha + thalassemia: 1 alpha gene is deleted which leads to a silent hematologic phenotype (-a/aa)
2. alpha-thalassemia trait: 2 alpha genes deleted which leads to a low mean cell volume, low mean cell Hb with normal fetal and HbA2
   (-a/-a pr –/aa)
3. HBH- 3 alpha genes are affected (-a/–); leads to severe anemia
4. Hydrops fettles with Hb Bart’s- both alpha genes are completely inactivated (–/–)

Question 6

Describe the positive cooperativity that is involved in hemoglobin/ O2 binding?

Answer 6

as soon as one O2 molecule binds, it increases the affinity of the next O2 molecule binding through the pulling of the proximal F* histidine

Question 7

Which form (T or R) does 2,3-BPG stabilize?

Answer 7

T form; which causes a low affinity in the Hb which releases oxygen

Question 8

What causes the sigmoidal shape of hemoglobins oxygen dissociation curve?

Answer 8

interactions between the subunits

Question 9

Describe embryonic hemoglobins

Answer 9

-expressed in the yolk sac until 8 weeks

Question 10

Describe sickle cell anemia in detail

Answer 10

1. HbS is caused by an amino acid switch at amino acid position 6 and there is a substitution; glutamic acid for valine
2. causes polymerization of hemoglobin which causes a sickle shaped RBC which is hard for the oxygen to bind

Question 11

What are the 4 global chains that are in the normal adult?

Answer 11

alpha
beta
delta
gamma

Question 12

Describe the role of 2,3 BPG in active tissues

Answer 12

there is a lot of it present in active tissues that causes the hemoglobin to let go of the O2 by binding to the central pore of the deoxyhemoglobin

Question 13

Describe what happens when the oxygen binds to hemoglobin in regards to structure

Answer 13

• changes the position of the iron atom and moves into the plane of the heme
• this action pulls the F8 proximal histidine which is attached to the globulin change; which contribute to function

Question 14

Describe the characteristics of hydrops fetalis including the genetic cause and type of Hb made along with the clinical presentation.

Answer 14

caused by a COMPLETE inactivation of the alpha genes, causing the fetus to make gamma tetramer Hb, which has a high affinity for O2 (so the mothers oxygen is delivered to the fetus BUT it does not want to give it up, and therefore does not deliver it to the tissues)

This leads to severe hypoxia and still born or death shortly after birth

severe edema results and CHF; hepatosplenomegaly

Question 15

Describe the T and R forms of Hb

Answer 15

T-tense (non-oxygenated)

R-relaxse (oxygenated)

Question 16

Describe the structure of hemoglobin

Answer 16

multi-subunit protein that has a heme per subunit; which is able to carry oxygen

Question 17

Describe the thalassemias

Answer 17

most common diseases : insufficient globulin chains produced;

can occur in alpha or beta

Question 18

Describe HbA1c and talk about its relationship to diabetes

Answer 18

• caused by a post-translational modification of the globulin chain in which a glucose is added (irreversible)
• in people with diabetes (poorly controlled esp), if their blood sugars are high and uncontrolled, you would expect to see

Question 19

Define HbH

Answer 19

with the lack of alpha subunits (due to thalassemia) there is an increase in beta tetramers

• alpha global synthesis is 25-35% normal levels
• hemolytic anemia

Question 20

Describe fetal hemoglobin

Answer 20

made predominantly in the liver; in the fetus this is about 90-95% on the total Hb production

Question 21

Describe beta thalassemia

Answer 21

• reduced B chains
• excess a chains which cause damage to RBCs which leads to anemia

can either be no B chain expression (major) or partial B expression (minor)

Question 22

Define Hb Bart’s

Answer 22

result of alpha thalassemia which affects the fetus; there is an increase in gamma tetramers due to the decreased alpha

Question 23

Describe 2,3 bisphophoglycerate (23 BPG)

Answer 23

intermediate by product of glycolysis

present in RBC at the same concentration of Hb; makes hemoglobin efficient

Question 24

What is the predominant form of hemoglobin?

Answer 24

HbA which has 2 alpha and 2 beta subunits

Question 25

Define myoglobin

Answer 25

monomer that is encoded by different genes. Has one Fe2+

STORES O2 (important in muscles) which hemoglobin is an O2 transporter

Question 26

What are the 3 types of hemoglobin that are present in humans?

Answer 26

embryonic
fetal
adult

Question 27

Describe the relationship between hemoglobin and pH (Bohr effect)

Answer 27

as the pH decreases, the affinity for O2 is also decreased; When an H+ is present, the amino acid will pick it up and that will change the conformation of Hb, releasing O2

Question 28

Describe what 2,3BPG does to the oxygen dissociation curve

Answer 28

makes it sigmoidal and shifts it to the right

Question 29

List the global chains that are alpha like chains.

AND what chromosome are they found on?

Answer 29

zeta
alpha

Chromosome 16

Question 30

Describe adult hemoglobin

Answer 30

starts being produced after birth

newborn: 50-85% HbA, fully adult at 1 year

Question 31

What is the function of erythrocytes?

Answer 31

transport oxygen from the lungs to the tissue

Question 32

Describe erythropoiesis

Answer 32

2/3 of the hemoglobin is made prior to nucleation. The other third is made in the reticulocyte; globulin synthesis

Question 33

Describe the heme group that is present in the hemoglobin

Answer 33

1. gives blood color
2. has an organic component (protoporphyrin) and an iron center
3. has4 pyrrole rings that form a tetrapyrrole ring
4. iron is at the center of this bonded to nitrogen atoms

Question 34

Describe HbF

Answer 34

does not bind well to 23BPG which means a higher affinity for oxygen;

mostly present in the R form (high affinity for O2)

Question 35

Describe Hydrops fettles with Hb Bart’s

Answer 35

make a gamma 4 Hb which is bad news

-stillborn or die a few hours after birth because no oxygen

they have a high affinity for O2 but are not able to drop it off in the tissues which leads to severe hypoxia and leads to CHF And edema

Question 36

Describe the concept of tissue switching

Answer 36

During development, the fetal red blood cells are created in the liver, spleen, and yolk sac. BUT when the baby is born, it starts being made in the bone marrow

Question 37

Describe the histidines that are present within hemoglobin…

1. who is the most proximal histidine?
2. who is the distal histidine?

Answer 37

1. F8

2. E7 (binds the O2)

Question 38

Describe carboxyhemoglobin

Answer 38

occurs when the heme binds to CO (210 times stronger than the O2 Hb bond)

causes a decreased transport of oxygen to the tissues

Question 39

Describe the reversibility of the binding of oxygen

Answer 39

Once one is lost, there is an increased chance that the other subunits will also lose their oxygen

Question 40

Which pair of globin chains makes up the majority of hemoglobin found in the normal human fetus?
– A. a2b2 
– B. a2g2 
– C. a2d2 
– D. z2b2 
– E. a1g3

Answer 40

B