Biol/Chem 5310
Lecture: 11
October 1, 2002
Hemoglobin-Example of a Protein
A) Concepts of Protein Structure
B) New Concepts
C) Biological Interest
D) Current research
Max Perutz devoted his scientific career to the study of Hemoglobin. He won the Nobel Prize in Chemistry in 1962
Physiological role of Myoglobin and Hemoglobin (Protein Structure)
Mb: single polypeptide, 17,000 MW, one heme, one O2 binding site, found in tissues, stores and transports O2, facilitates diffusion of O2 from blood to tissues (Mb structure)
Hb: 4 polypeptide chains, a2b2-tetramer, each is similar in sequence and 3-D structure to Mb, 4 hemes, 4 O2 binding sites, found in red blood cells, binds O2 in lungs, delivers O2 to tissues, also carries CO2 from tissues to lungs
O2 binding by Mb
define dissociation constant: K (units of Molar)
Define saturation, Y as sites occupied divided by sites available :
rewrite Y in terms of K and [O2]
work this out for yourself (Check)
So, fractional saturation is governed simply by the concentration of O2 and by the dissociation constant K
Since O2 is a gas, we can replace [O2] by pO2, the partial pressure
and replace K by P50, where P50 is defined as the partial pressure of O2 when Y is 1/2 , (50% saturation)
Dissociation constant is concentration of O2 when Y = 1/2
Like: pKa is pH when Y = 1/2, ([A-] = [HA])
To show this: solve for pO2 when Y=1/2 (Check)
A plot of Y vs. pO2 is hyperbolic
It is easier to work with a straight line plot
log () = log pO2 - logP50
This is the Hill equation
For Mb, slope of Hill plot is 1.0
Why Hb cannot be 4xMb, if it must function as a delivery system of O2 from lungs to tissues
Binding Equation for Hb
These equations are much more complex, in general. For simplicity we will consider the special case of infinite cooperativity: all O2 molecules bind at once.
Hb + 4 O2 <--> Hb(O2)4
- This leads to a general Hill equation and Hill plot for n ligands:
- log (Y/1-Y) = nlogPO2 - nlogP50
- For infinite cooperativity, the maximal slope of the Hill plot will equal the number of binding sites, i.e.4 for Hb
- In reality, it is never that high, and is called nH, the Hill coefficient
- For Hb, it is 2.8-3.0
- And the Hill plot does not yield a straight line, but the maximal slope of the line is the Hill coefficient, nH
- The Hill coefficient gives a measure of the cooperativity
- nH < or = n (nH must be less than or equal to the number of binding sites)
- if nH = 1, there is no cooperativity, e.g. Mb
- if nH > 1 , positive cooperativity, e.g. Hb
- if 0 < nH <1 , negative cooperativity
Carbon Dioxide Transport and the Bohr Effect
See the Animation of Fig. 7-12 (Bohr Effect)
See the Animation of Fig. 7-14 (CO2 and BPG Effect)
Last updated
Comments/questions: svik@mail.smu.edu
Copyright 2002, Steven B. Vik, Southern Methodist University