Lecture 11 - Hemoglobin Flashcards
What is the structure of hemoglobin?
L11 S8
- 2 α-globulin chains
- 2 β-globulin chains
- 4 heme group (one per globulin subunit)
What types of hemoglobin subunits are there?
L11 S10
α-like chains:
- ζ (zeta) embryonic
- α (alpha) (α1 and α2 variants)
β-like chains:
- ε (epsilon) embryonic
- γ (gamma) fetal (glycine and alanine variants)
- δ (delta)
- β (beta)
What types of hemoglobin are there and what subunits are they made of?
L11 S12;14
Embryonic:
-ζ2ε2
Fetal (HbF)
-α2γ2
Adult (HbA)
-α2β2
Sickle cell (HbS)
- α2β2
- substitution of AA 6 from valine to glutamic acid
What is the general structure of the heme group?
L11 S17
Protoporphyrin:
- 4 pyrole rings which form a ring
- various side chains
Iron atom located centrally in ring
What is the general structure of hemoglobin subunits?
L11 S22
-8 helical regions labeled A-H
What are the important AAs in hemoglobin and what do each do?
L11 S23-24
Proximal histidine:
- F8 histidine
- binds heme group
- pulled when oxygen is bound causing conformational change (cooperativity)
Distal histidine:
- E7
- hydrogen bonds with oxygen
Differentiate between myoglobin and hemoglobin?
L11 S34
Myoglobin:
- storage
- monomer
- holds one O2
- stronger affinity for O2 (50% at 2 torr)
- hyperbolic dissociation curve
Hemoglobin:
- transportation
- tetramer
- holds four O2
- lower affinity for O2 (50% at 25 torr)
- sigmoidal dissociation curve
What is the positive cooperativity and reversibility of hemoglobin?
What is responsible for these effects?
L11 S40
Positive cooperativity:
- binding of O2 to a heme group causes a conformation change by pulling on proximal histidine
- this increases the affinity of the other heme groups.
Reversibility:
- loss of O2 from a heme reverts conformational change via proximal histidine
- this decreases the affinity of the other heme groups
What is 2,3-BPG and what is its role in oxygen transport?
L11 S49
Allosteric modulator of hemoglobin.
Stabilizes T form of hemoglobin which has lower affinity for oxygen.
It is present in high concentration in tissues as it is an intermediate of glycolysis. This causes oxygen to be released in tissues.
It is present in low concentration in the lung. This causes oxygen to be stored.
ALSO PRESENT IN HIGHER LEVELS IN SMOKERS CAUSING DECREASED O2 AFFINITY.
What are the different forms of hemoglobin and what is the significant difference between the two?
L11 S51
T (tight) form:
- low affinity for O2
- β chains are further apart
- stabilized by 2,3-BPG
R (relaxed) form:
- high affinity for O2
- β chains are closer together
What affect does pH have in oxygen transport?
L11 S54
Oxygen affinity decreases with decreased pH.
This is due to a conformational change that occurs when an AA accepts a H+.
The pH of metabolically active tissues is lower and therefore increases O2 release from hemoglobin.
Carbon monoxide has a 210 times stronger affinity for heme than O2.
It can replace oxygen at low concentrations and cause suffocation.
Just know it has a higher affinity
What HbA1c and what is the significance of this?
L11 S60
Post-transcriptional, irreversible modification of β-globin chain by addition of glucose.
Normal HbA1c level is 3% but it is directly related to blood sugar level and is 6-9% in diabetics.
Lasts for lifespan of RBC so can indicate level of recent diabetic control.
Differentiate between α-thalassemia and β-thalassemia.
L11 S65
α+-thalassemia:
- 1/4 α-globin genes affected
- silent or mild symptoms
α-thalassemia trait:
- 2/4 α-globin genes affected
- low MCV and MCH
HbH disease:
- 3/4 α-globin genes affected
- moderate-severe anemia
- low MCV, low MCH, hemolytic anemia, hepatosplenomegaly, mild jaundice
- β4 tetramers
Hydrophobic fetalis w/ Hb Barts:
- 4/4 α-globin genes affected
- stillborn or die soon after birth
- Bart’s hemoglobin, γ4, which has too high an affinity for O2
β-thalassemia major:
- 0% β-globin synthesis
- severe anemia onset at age of 2
- α-globin can’t form tetrameres
β-thalassemia minor:
- 50% β-globin synthesis
- mild anemia
