Lecture 17: The rest Flashcards
What is 2,3-Bisphosphoglycerate (BPG) essential for?
The formation of the T state of Hb
What happens if there is no 2,3-Bisphosphate present?
Hemoglobin doesn’t adopt the T state
What would the oxygen binding curve of Hb look like without BPG present?
It would be hyperbolic
What is the charge of BPG?
It carries a strong negative charge
What kind of effector is BPG?
It is a negative allosteric effector
What does BPG do to hemoglobin?
It decreases Hb’s affinity for O2
What state does BPG bind to?
The T-state
How many BPG binding sites are there for each Hb?
There is one BPG binding site for each Hb
What is the BPG binding sites found between?
Between the subunits of the hemoglobin quaternary structure
What cavity does BPG bind in?
The central cavity of deoxyhemoglobin
What do the negative charges on BPG interact with?
Positively charged groups on the protein that are directed into the central cavity
What positively charged groups interact with BPG?
- 4 Lysine
- 2 Lysine
- 2 N-terminal residues
What is the size of the central cavity of the hemoglobin in the T state and in the R state?
In the T state the cavity is larger
Which direction would a negative allosteric inhibitor shift a hemoglobin binding curve?
It would shift the curve right
What ions does Metabolism generate?
Protons
Through what reactions does BPG increase protons (lower pH)?
- ATP + H2O ➡️ ADP + P + H+
* CO2 + H2O ➡️ HCO3- + H+
How does lowering the pH affect the side chains of Hb functional groups?
It causes protonation
•His + H+ ➡️ His+
•-NH2 + H+ ➡️ NH3+
What happens when groups associated with BPG binding become protonated because of low pH?
They Enhance BPG binding and reduce O2 binding
What happens to carbon dioxide when it appears in the blood stream?
It is converted to carbonic acid which lowers the pH in the blood stream
How is the subunit interface in hemoglobin affected by lower pH?
New electrostatic interactions form
What is the Bohr effect?
- Enhance binding of BPG and reduced binding of O2 associated with increased protons
- Hemoglobin subunit interface forming new electrostatic interactions
What is the difference in pH between the blood in the lungs and in skeletal muscle?
•The pH of blood in the lungs is 7.6
•The pH of blood in skeletal muscle is 7.2
Blood in skeletal muscle is more acidic
How is oxygen binding affected by an increase in proton concentration?
There will be a decrease in oxygen binding behavior
How is oxygen binding affected by an decrease in proton concentration?
There will be increased oxygen binding
