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 binds at the heme:

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

  • Mb has high affinity for O2.
  • If Hb were like 4xMb, it would be saturated with O2 in the lungs, but it would not release much O2 in the tissues, because its affinity would be equally high as Mb's
  • If Hb were like 4xMb, but with lower affinity for O2, it could release O2 in the tissues, but it would have difficulty loading O2 in the lungs, because its affinity would not permit it.
  • It is essential that Hb's saturation curve for O2 binding be sigmoidal, rather than hyperbolic.

    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

    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 Friday, September 27, 2002

    Comments/questions: svik@mail.smu.edu

    Copyright 2002, Steven B. Vik, Southern Methodist University