Hemoglobin and Ligand Binding
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- What is fractional saturation?
- The proportion of total sites filled.
- Dalton's Law
- Total pressure of gas mixture is sum of partial pressures
- Henry's Law
- Concentration of gas in solution proportional to partial pressure
- What are the pressure units?
- 1 atm = 760 mm Hg = 101 kPa
- K sub D or equilibrium constant/dissociation constant equation
-
= [L] [P]/ [PL]
where P is protein, L is ligand, and Ptotal = P + PL. Binding is "tight" when affinity is high, KD is low. - fractional saturation equation
-
Θ = [L] / [L]+KD
Sites are half saturated (Θ=0.5) when [L]=KD - Does oxygen bind to heme embedded in protein reversibly?
- Yes.
- P50 is ....
- is PO2 where protein in 50% saturated (=KD)
- What happens when Fe(II) is oxidized to Fe(III)?
- O2 binding is abolished.
- What is cooperative binding?
- When multiple, interacting sites, whose affinity changes as more sites have O2 bound. An example of "allostery."
- What stabilizes the R state of Hb?
- O2 binding. R has a higher affinity for O2.
- What is the Hill equation?
-
For a protein P having n sites that bind ligand L:
Θ = [L]n / ([L]n + Kd )
Log of equation = Log (Θ/ 1- Θ) = n log [L] – log Kd - How does pH affect O2 affinity for Hb?
- O2 affinity of Hb declines with pH (Bohr effect). Example: acidosis in exercising muscles induces O2 release (getting more oxygen to muscles)
- How does CO2 affect Hb?
- CO2 carbamylates Hb, stabilizes T-state, promotes release of O2
- How does BPG binding affect O2 affinity?
- BPG greatly reduces the affinity of Hb for O2. Important when at high altitudes.
- What mutation causes Sickle Cell Disease?
- Glu to Val at residue 6 of β subunits.
- What promotes sickling?
- Dehydration, exertion (hypoxia)
- Why are Hb levels low (50% normal)?
- Sickled cells are fragile and rupture easily.
- What concentration of CO is considered to be fatal?
- 50 - 60 % COHB is considered fatal
- How would you treat CO poisoning?
- with excess O2. 100% O2 is good, hyperbaric oxygen (3 atm) is better