Introduction

    Hemoglobin (Hb) and myoglobin (Mb) are
            oxygen binding proteins.

        Hemoglobin is found in the red blood
                            cell (RBC).

            It carries oxygen from the lungs to
                            the tissues.

        Myoglobin is found in muscle, primarily
                        skeletal muscle.

            It stores oxygen for use during exercise.

Properties of gasses.

    The concentration of gasses is measured in
            partial pressure (Torr = mm Hg).

        The total pressure of a mixture of gasses
            is equal to the sum of the partial
               pressures of each gas. (Dalton’s Law).

    The atmospheric pressure is 760 Torr.

        Air is 20% oxygen, and therefore the
         partial pressure of oxygen in the air
                                              is 152 Torr.

        The partial pressure of oxygen in the lungs
            is 100 Torr due to mixing of inspired
                air with residual air in the lungs.

        The partial pressure of oxygen in the tissues
            varies with the tissue, but in skeletal
                muscle it averages about 20 Torr.

Structure of Hemoglobin

                               Being an oligomeric protein, Hb has
                            quaternary structure.

            Myglobin consists of a single amino
                acid chain, similar in structure
                                      to both subunits of Hb.

        Each subunit of Hb (and Mb) has a heme
            ring and an iron ion (Fe⁺²) as a
                    prosthetic group.

            The heme ring is a tetrapyrole.

            Thus, each Hb can bind 4 O₂.

Oxygen binding by Hemoglobin.

    If we plot the oxygen binding curve for Hb,
        the x-axis goes from zero, through 20
                            to 100 Torr.

          Conceptually we are dealing with a large
                number of hemoglobin molecules
                    inside a single red blood cell.
 

              If we were dealing with a single Hb
               molecule, there would only be five
                discreet values possible, 0, 25, 50,
                            75, and 100 %.

Hemoglobin/Oxygen dissociation curve:
 
 
 
 
 
 
 
 
 
 

            We can define the P₅₀, which is the
                partial pressure of oxygen at
                 which Hb is 50% saturated.

            The P₅₀ resembles the K_m in that
                it is inversely related to the
                                   affinity of Hb for oxygen.

        Note that this curve has an S-shape,
           implying that Hb has properties
                       similar to allosteric enzymes.

            One such property is cooperativity of
          binding. This means that as one oxygen
         binds it makes it easier for the next, until
            the molecule is saturated with oxygen.

        The myoglobin/oxygen dissociation
       curve is not sigmoidal, indicating that
         there is no cooperativity of binding.

            The Hill Coefficient quantifies the
                    degree of cooperativity.

                Hb has a Hill Coefficient of about
                    3.0, indicating cooperativity.

                Mb has a Hill Coefficient of exactly
                    1.0, indicating no cooperativity.

Oxygen transport.

    In the lungs, at 100 Torr, all Hb in a single
               RBC is saturated with oxygen.

    As the RBC leaves the lungs, and encounters
        lower partial pressures of oxygen, the Hb
            molecules release their oxygen, and
                  thus become less saturated.

        This results in the delivery of oxgen to the
            tissues. In the tissues, the Hb in the
                RBC is about 20 % saturated,
        corresponding to an 80% oxygen delivery.

    Note that at 20 Torr. Mb is almost 100%
        saturated, so as Hb releases its oxgen
            the oxygen is taken up by Mb.

Role of Bisphosphoglycerate (BPG).

    The cooperativity of Hb is dependent upon
        the presence of BPG. If Hb is stripped
            of its BPG, its dissociation curve
                    resembles that of Mb.

    Note that under these conditions, Hb would
     be useless as an oxygen transport protein in
            the body, because it would deliver
                           almost no O₂.

Effect of pH.

    Like allosteric enzymes, Hb is sensitive to
        its environment. As the pH decreases,
    the Hb/Oxygen dissociation curve shifts to
          the right, i.e. the P₅₀ increases.

            This is sometimes called the Bohr effect.

            This reduces the affinity of Hb for O₂.

        The net effect is to increase oxygen delivery
                                to the tissues.

    Increasing the concentration of CO₂ will
        cause the same shift (Root effect).

    CO₂ + H₂O ßà H₂CO₃ ßà H⁺ + HCO₃^-

        The Root effect can thus be seen as just
                an extention of the Bohr effect.

    Increasing the BPG concentration will cause
        the same shift, and this is important in
            acclimatization to high altitude.

Fetal Hemoglobin.

    Fetal hemoglobin consists of two alpha
         subunits and 2 gamma subunits.

    Its Hb/O₂ dissociation curve is just to the
                left of the adult Hb curve.

        Thus, fetal Hb has a slightly higher affinity
            for oxygen, and oxygen is pulled from
                the maternal circulation across the
                 placenta into the fetal circulation.