Hemoglobin Flashcards
Water solubility between polar and nonpolar molecules
Polar = very soluble (ammonia, hydrogen sulfide)
Nonpolar = not soluble (O2, N2, CO2)
—> therefore need transport of these in our blood and EC fluids
—> done by myoglobin and hemoglobin
Hemoglobin (general)
Facilitates circulation of O2 and CO2 in our blood
Hb bind to O2 in the lungs at a higher pH and releases O2 to the tissues at a lower pH
CO2 is picked up by Hb in the tissues and carried to lungs for expiration
Myoglobin (general)
Facilitates the diffusion of O2 (and its storage) to and from the tissues
Mb binds to O2 more tightly than Hb
Affinity for O2 is NOT affected by pH or modifying molecules (like Hb)
Basis of the difference between Hb and Mb is in the structure
Heme structure
Both Hb and Mb have an heme prosthetic functional group
Heme = protoporphyrin IX ring with a ferrous iron (Fe2+) coordinated at its center
Fe2+ binds to the O2
Fe2+ can form six bonds
—> 4 = to the ring
—> 5th = to a histidine side chain
—> 6th = to O2
The histidine side chain can move laterally…moves the Fe2+ in/out of the plane of the ring
Subunits between Hb and Mb
Mb = monomer, single protein and single heme
Hb = heterotetramer, four subunits
—> 2 alpha-globin
—> 2 beta-globin
Each subunit has a central heme group
Equilibrium dissociation constant (Kd)
The concentration of the ligand at which 1/2 of the available ligand binding sites are occupied
Smaller Kd = higher affinity the protein has to the ligand (binds tighter)
Binding curve for myoglobin
Hyperbolic
Suggesting that Mb = one binding site
O2 binds very rapidly to Mb
Low Kd
Binding curve for Hb
Sigmoidal
Cooperative binding (multiple binding sites)
Higher Kd than Mb
Affinity get increasingly exponential as more binding sites are occupied…then levels off once 4th in occupied
Tense and relaxed states of hemoglobin
All related to the Fe2+ position
Fe2+ bound to a histidine side chain in one of the alpha-helices in Hb
Each subunit can exist in either state
Relaxed = histidine is positioned such that the Fe2+ is evenly situated in the plane of the ring —> conformation has a higher affinity for O2
Tensed = histidine positioned such that the Fe2+ is out of the plane of the ring —> lower affinity
Mechanism of changing conformation of hemoglobin
Answer lies in the 8 ionic bonds that exist in the T-state
6 of them = interchain ionic bonds between different subunits
2 = intrachain ionic bonds
They hold the subunits in tensed state
As the[O2] increases…the first O2 will eventually bind to one of the heme groups…this breaks two of the ionic bonds —> generating a more relaxed conformation
—> makes it easier to bind a 2nd…and so on
Less ionic bonds = easier for histidine to move Fe2+ to plane of the ring
Molecules that help binding of O2 to Hb
Increase [O2]
Raise pH (more basic environment - like lungs)
Lower [Co2]
Higher [CO] = bad
Low [BPG]
Molecules that hurt binding of O2 to Hb
Low [O2]
Low pH
High [CO2]
Low [CO] = good
High [BPG]
Why does low pH lower affinity of O2 to Hb
Acidic pH favors ionization and strengthens the ionic interactions of the T-state
Once CO2 enters the plasma from the tissues…it has 3 fates
- 10% remains dissolved in the plasma and is transported to the lungs in that form…rest diffuses into the RBCs
- 23% of the RBC CO2…forms readily reversible, non-covalent adduct with the four amino terminal end of the four subunits of Hb = ‘carbaminohemoglobin’….converted back to CO2 and Hb in lungs
- Rest of CO2 (70% total) and water converted to bicarbonate (HCO3-)
—> catalyzed by carbonic anhydrase (CA)
—> converted back to CO2 and water in lungs
CO poisoning
CO binds Hb ~250x more tightly than does O2
CO also stabilized the R-state of Hb
Prevents O2 from being off loaded and delivered to tissues
Early symptoms = confusion, fatigue, nausea, headache
