Chapter 9 (Exam 2) Flashcards
(27 cards)
What are globins?
Oxygen-binding proteins.
What is myoglobin?
Muscle protein.
Heme-containing monomeric protein.
Major function is to store O2.
What is hemoglobin?
Major protein of red blood cells.
Heme-containing tetramer (4 polypeptide chains; 2a + 2b).
Major function is to carry O2 from lungs to tissues.
What does the heme group consist of?
An organic component called protoporphyrin and a central iron ion in the ferrous (Fe2+) form.
Where is the iron located in the heme structure?
In the middle of the protoporphyrin.
Has 6 coordination bonds: 4 in the plane of porphyrin ring bound to nitrogens and 2 perpendicular to it (5th and 6th coordination sites).
What is the 5th coordination site occupied by?
Proximal histidine: imidazole ring of a histidine.
What does the 6th coordination site bound to?
Oxygen.
What happens upon oxygen binding?
Iron moves into the plane of the protoporphyrin ring.
How does oxygen binding change the position of the iron ion?
The iron ion lies slightly outside the plane of the porphyrin in deoxyhemoglobin heme but moves into the plane of the heme on oxygenation.
What is hemoglobin?
A tetramer of 2 identical dimers (a2b2).
What must vary for effective transport?
Affinity with pO2.
How can affinity to oxygen change?
It must be a protein with multiple binding sites.
Binding sites must be able to interact with each other.
The phenomenon is called cooperativity.
What is cooperativity?
Positive cooperativity:
- First binding event increases affinity at remaining sites.
- Recognized by sigmoidal binding curves.
Negative cooperativity:
- First binding event reduces affinity at remaining sites.
What affinity to O2 does Hemoglobin have at R and T states?
T state: lower affinity to O2.
R state: higher affinity to O2.
What is the T state of Hemoglobin?
Tense state.
More interactions, more stable.
Lower affinity for O2.
What is the R state of Hemoglobin?
Relaxed state.
Fewer interactions, more flexible.
Higher affinity for O2.
What does O2 binding trigger?
T –> R conformational change.
What is a special case of allosteric regulation?
Cooperativity.
What is an allosteric protein?
Binding of a ligand to one site affects the binding properties of a different site on the same protein.
Can be positive or negative.
Homotropic: normal ligand of the protein is the allosteric regulator.
Heterotropic: different ligand affects binding of the normal ligand.
What is positive homotropic regulation?
Cooperativity.
What if 2,3-BPG bind to?
The Central Cavity of hB.
How does 2,3-Biphosphoglycerate regulate O2 binding?
Negative heterotropic regulator of Hb function.
Present at mM concentrations in erythrocytes.
- Produced from an intermediate in glycolysis.
Small negatively charged molecule binds to the positively charged central cavity of Hb.
Stabilizes the T states.
What is the pH effect on O2 binding to hemoglobin?
Actively metabolizing tissues generate H+, lowering the pH of the blood near the tissues relative to the lungs (catalyzed by carbonic anhydrase).
CO2 + H2O –> HCO3- + H+.
What does Hb affinity for oxygen depend on?
The pH.
H+ binds to Hb and stabilizes the T state, which leads to the release of O2 (in the tissues).
