Term 1- Lec 4- Hb & Mb Flashcards
Myoglobin location and basic function
Heart and skeletal muscle, and small amounts of smooth muscle. Stores O2.
Hemoglobin location and basic function
Erythrocytes. Delivers O2 from the lungs to tissues and CO2 from the tissues to the lungs.
Which Iron cation is bound to the heme group in hemoglobin
Fe2+ (Ferrous iron). Methemoglobin–bound to Fe3+ (Ferric iron) does not bind O2.
What binds to the 5th coordination site of Heme?
Proximal histidine
What stabilizes O2 when it’s bound to the 6th coordination site of Heme?
Distal histidine
Why is the Heme group necessary, and not just Fe2+?
Binding only ionic iron is irreversible and would not function in O2 delivery
When does Myoglobin release it’s O2?
At very low O2 concentrations, only in the tissues. Hyperbolic dissociation curve
Mb and Hb O2 affinities in:1) Lungs, 2) Tissues
They both have similar, high affinity for O2 at lung concentrations. They differ in tissues, Mb keeps most of it’s O2 in normal tissue concentrations, doesn’t release until the tissues are below their normal O2 levels. Hb unloads it’s O2 in the normal tissue concentration
T state
Lowered affinity for O2, takes this shape when unbound to O2 (most often in tissues). Named deoxyhemoglobin
R state
Significantly higher affinity for O2, takes this state when in the lungs. Named oxyhemoglobin
How does binding O2 change the conformation of Hemoglobin?
3º structure changes thus 4º structure changes too. O2 Pulls Fe into plane of porphyrin ring, Fe pulls proximal His forward, F helix moves as well do to steric repulsion.
Cooperativity in Hemoglobin
O2 binds to one subunit, stabilizing it in that state AND pressuring the other subunits to adopt the shape thus raising it’s affinity toward O2.
Allosteric regulation requires
4º structure (at least 2 proteins)
Homotropic
The effector ligand is identical/very similar to the true ligand
Heterotropic
The effector ligand is different from the true ligand
Negative effectors
Inhibitors- decrease protein activity. Shift binding curves to the right. Decreased affinity allows for more O2 to be released in the tissues.
Poitive effectors
Activators- Increase protein activity. Shift the binding curve to the left
The ligands for Hemeglobins
2,3-BPG, CO2, H+ (Bohr’s effect)- negative effectors. CO- positive effector (but bad).
2,3-BPG affect on Hb
2,3-BPG is a negative allosteric effector of Hb. It stabilizes the T state by binding through inoic bonds in the central cavity “holding it open”. Only fits in center when Hb is in T state. Promotes release of O2.
Fetal Hb has higher affinity to O2 than Adult Hb because:
HbF cannot bind 2,3-BPG, thus, without the negative effector, it has higher affinity
CO2 affect on Hb
CO2 is a negative allosteric effector of Hb. It binds N-terminus of Hb via an ionic bond (negatively charged now) stabilizing.
In what form does CO2 get to the lungs?
20% of exhaled CO2 is transported as CO2 bound to the N-terminus of Hb. Most (75%) CO2 is transported as bicarbonate (HCO3-)
What does a graph look like of Hb with negative effectors bound to it?
The sigmoidal curves shift right. CO2 the least, 2,3-BPG more than CO2, the two combined make the furthest curve.
H+ effect on Hb-Bohr Effect (in tissues)
H+ is a negative allosteric effector. It binds at a His of the ß-subunit, changing the protonation state. Increased [H+] = increased O2 delivery.
H+ effect on Hb-Bohr Effect (in lungs)
H+ increase the amount of CO2 exhaled. [O2] is so high that O2 automatically saturates Hb. Binding O2 releases H+ —> HCO3- + H+ —> H2CO3 —> H2O + CO2 (via CARBONIC ANHYDRASE)—> CO2 is exhaled.
Hb affinity to CO
Much, much higher than it’s affinity to O2
CO effects of binding to Hb
Binds to same site as O2 and increases affinity for O2, but locks the Hb in the R state and does not release the O2 in the tissues- acts as storage. CO shifts the saturation curve LEFT.
