Lecture 9: Myoglobin/Hemoglobin Flashcards
Myoglobin and Hemoglobin
Define Cooperativity
Example?
In multisubunit proteins, conformational changes in one subunit can affect the others (up or down)
Hemoglobin’s sigmoidal curve following binding/release of O2
Why must transition metals be contained within groups, e.g. why can’t they free float through the body bound to O2?
Their bonding would generate harmful free radicals
Where is myoglobin found?
Muscle
What causes hemoglobin to have greater oxygen deliver and release?
Tetrameric Structure
At low Oxygen levels, which will have bind faster–myoglobin or hemoglobin?
Myoglobin
How are the structures of hemoglobin and myoglobin similar and different?
Myoglobin is single polypeptide, Hemoglobin is a tetramer
Each polypeptide of hemoglobin is similar to myoglobin, and each contains a heme.
They have completely different amino acid primary sequences.
What is the overall structure of hemoglobin?
α2β2 tetramer
a = 141 AA
b = 146 AA
What is the prosthetic group in hemoglobin and myoglobin?
Oxygen will only bind to what state of Fe?
Porphyrin, which binds to an Iron (Fe) atom–resulting in Heme
(+2) Oxidation State
What is the result of O2 binding to Fe2+ in Heme in Myoglobin?
What ligand does the Iron move toward?
The Fe atom is pulled closer into the porphyrin ring, causing conformational changes
Proximal Histidine
What are the characteristics of the T-state of Hemoglobin?
T = TENSE state
More interactions
More stable
Lower Affinity for O2
Think Muscles here
What are the characteristics for the R-state of Hemoglobin?
R=RELAXED
Fewer Interactions, more flexible
Higher Affinity for O2
Think Lungs Here
What is the difference between Positive and Negative cooperativity?
Positive: First event INCREASES affinity for remaining sites
Negative: First event DECREASES affinity for remaining sites
An increase in [H+] causes what change to hemoglobin?
Release O2
What state is stabilized by 2,3-BPG?
T-State (deoxy Hb)
What conformational change does pH have on Hemoglobin?
As pH decreases, H+ becomes available to protonate His146 which forms a salt-bridge with Asp94
Stabilizes the T-state
O2 is released at the tissues
What does the pH difference between the lungs and tissues result in?
Efficiency of O2 transport; favors release in tissues and uptake in lungs
What role does Hemoglobin have in CO2 management?
What does this result in?
How is the majority of CO2 exported?
- 15-20% exported via carbamate on the amino terminal residues
- Increased H+ concentration (release of O2)
- Further salt bridges (stabilize T-state)
- Disolved bicarbonate
What is the source is much CO2 in the tissues?
What role does this have?
By-product of the Krebs Cycle
Increases release of O2 by hemoglobin
Why is it important for 2,3-BPG to be released in the placenta?
HbF has a much lower affinity for 2,3-BPG; however the placenta gives extra O2 which can bind with HbF
Why does CO bind 20,000x greater than O2 to Hb?
What can lower this ratio to 250x greater?
What are the physiological results of bound CO?
Forms triple bond
Distal-Histidine in the protein pocket
Hint: DIKEMBE Histidine
Blocks function of myoglobin, hemoglobin, and mitochondrial cytochromes
What are the structures for:
Normal Adult HbA:
HbA2:
Sickle Cell HbS:
Infant HbF:
HbA1C:
HbA: α2β2
HbA2: α2δ2
HbS: α2βs2
HbF: α2γ2
HbA1C:α2β2-glucose
Why does HbF have a higher affinity for O2?
Why is this non-optimal postpartum?
It must extract oxygen from the mother’s blood, so it must have a greater affinity than HbA
This greater affinity would result in low quantities of oxygen delivered to the tissues post-partum
What is the cause of Sickle Cell Anemia (HbS)?
What is the half life for an HbS RBC?
Hb Glu -> Cal 6
(polar to non-polar)
20 days
What is source of Hemoglobin C?
What is source for Hemoglobin SC?
Conversion of Glu6 → Lys6 in β-globin gene
One β-globin gene codes for HbS, other HbC
