This document summarizes oxygen transport in blood and the factors that influence oxygen binding to hemoglobin. It discusses how hemoglobin transports oxygen by reversibly binding to it, and how oxygen dissociation curves describe this relationship. The curves are sigmoid for vertebrate hemoglobin and hyperbolic for other respiratory pigments. Factors like pH, temperature, CO2 levels, and organic phosphates influence the oxygen affinity by inducing conformational changes in hemoglobin. Together, these mechanisms facilitate oxygen loading in the lungs and unloading in tissues to meet metabolic demand.

1. Transport of O2 and CO2 between
respiratory surfaces
Abuzar Tabassum

2. Oxygen Transport in Blood
• Each hemoglobin molecule can combine with four oxygen molecules,
each heme combining with one molecule of oxygen.
• The extent to which O2 is bound to hemoglobin varies with the partial
pressure of the gas, PO2.
• If all sites on the hemoglobin molecule are occupied by O2, the blood is
100% saturated and the oxygen content of the blood is equal to its
oxygen capacity.
• A millimole of heme can bind a millimole of O2 which represents a
volume of 22.4 ml of O2.
• Human blood contains about 0.9 mmol of heme per 100 ml of blood.
• The oxygen capacity is therefore 0.9 x 22.4 = 20.2 vol %.

3. • Because the oxygen capacity of blood increases in proportion to its
hemoglobin concentration, the oxygen content commonly is expressed
as a percentage of the oxygen capacity, that is, the percent saturation.
• Oxygen dissociation curves describe the relationship between percent
saturation and the partial pressure of oxygen.

5. • The oxygen dissociation curves of myoglobin and lamprey
hemoglobin are hyperbolic, whereas the oxygen dissociation curves of
other vertebrate hemoglobin are sigmoid.
• This difference occurs because myoglobin and lamprey hemoglobin
have a single heme group, but other hemoglobins have four heme
groups.
• The sigmoid shape of the dissociation curves of hemoglobins having
several heme groups results from subunit cooperativity.
• Oxygenation of the first heme group facilitates oxygenation of
subsequent heme groups.

6. • The steep portion of the curve corresponds to oxygen levels at which
at least one heme group is already occupied by an oxygen molecule,
increasing the affinity of the remaining heme groups for oxygen.
• As a hemoglobin molecule is oxygenated, it goes through a
conformational change from the tense (T) state to the relaxed (R) state.

7. • At low PO2 only a small amount of O2 binds to the respiratory pigment; at high
PO2 however, a large amount of O2 is bound.
• Because of this property, the respiratory pigment can act as an oxygen carrier,
loading at the respiratory surface (a region of high PO2) and unloading at tissues (a
region of low PO2).
• In some animals, the predominant role of a respiratory pigment may be to serve as
an oxygen reservoir, releasing O2 to the tissues only when O2 is relatively
unavailable.

8. • During exercise, when the oxygen demand by the tissues is increased,
this venous reservoir of oxygen is tapped and venous saturation may
drop to 30% or less.
• Hemoglobins that have high oxygen affinities are saturated at low
partial pressures of oxygen, whereas hemoglobins with low oxygen
affinities are completely saturated only at relatively high partial
pressures of oxygen.
• The affinity is expressed in terms of the P50, the partial pressure, of
oxygen at which the hemoglobin is 50% saturated with oxygen; the
lower the P,, ,the higher the oxygen affinity.

9. • Myoglobin has a much higher oxygen affinity than hemoglobin.
• Variations in oxygen affinity among hemoglobins are related to
differences in the protein globin, not to differences in the heme group.
• For example, a genetic defect resulting in substitution of valine for
glutamic acid in position 6 of the β chain causes human hemoglobin to
form large polymers that distort the erythrocyte into a sickle shape,
giving rise to sickle cell anemia.
• Because these sickle cells cannot pass through small blood vessels,
oxygen delivery to tissues is impaired.

10. • Individuals with both normal and sickle cell hemoglobin suffer only
mild debilitation but have greater resistance to malaria, thus ensuring
the continuation of the sickle cell gene in the population.
• Certain amino acids in globin bind various ligands, and substitution of
these residues can cause changes in the oxygen affinity of hemoglobin.

11. • The rate of oxygen transfer to and from blood increases in proportion
to the difference in PO2 across an epithelium.
• A hemoglobin with a high oxygen affinity facilitates the movement of
O2 into the blood from the environment because O2 is bound to
hemoglobin at low PO2; i.e., O2 entering the blood is immediately
bound to hemoglobin, so O2 is removed from solution and PO2 is kept
low.
• Thus, a large difference in PO2 is maintained across the respiratory
epithelium-and therefore a high rate of oxygen transfer into the blood-
until hemoglobin is fully saturated.

12. • Hemoglobin with a high oxygen affinity, however, will not release O2
to the tissues until the PO2 is very low.
• In contrast, a hemoglobin with a low oxygen affinity will facilitate the
release of O2 to the tissues.
• From a functional viewpoint, therefore, hemoglobin should have a low
O2 affinity in the tissues and a high O2 affinity at the respiratory
surface.

13. • The hemoglobin-oxygen affity is reduced by the following:
• Elevated temperature
• Binding of organic phosphate ligands including 2,3 diphosphoglycerate (DPG),
ATP, or GTP
• Decrease in pH (increase in H+ concentration)
• Increase in CO2

14. • Increases in H+ concentration (decreases in pH) cause a reduction in
the oxygen affinity of hemoglobin, a phenomenon termed the Bohr
effect, or Bohr shift.
• Carbon dioxide reacts with water to form carbonic acid and reacts with
-NH2 groups on plasma proteins and hemoglobin to form carbamino
compounds.
• Thus an increase in PCO2 causes a reduction in the oxygen affinity of
hemoglobin in two ways:
• by decreasing blood pH (Bohr effect) and
• by promoting the direct combination of CO2 with hemoglobin to form
carbamino compounds.

16. • Therefore, when CO2 enters the blood at the tissues it facilitates the
unloading of O2 from hemoglobin.
• When CO2 leaves the blood at the lung or gill, it facilitates the uptake
of O2 by the blood.
• The oxygen dissociation curve for myoglobin, unlike that for
hemoglobin, is relatively insensitive to changes in pH.

17. • In some fishes, cephalopods, and crustaceans, an increase in CO2 or a
decrease in pH causes not only a reduction in the oxygen affinity of
hemoglobin but also a reduction in oxygen capacity, which is termed
the Root effect, or Root shift (Figure).
• In those hemoglobins showing a Root shift, low pH reduces oxygen
binding to hemoglobin, so that even at high PO2 only some of the
binding sites are oxygenated; that is, 100% saturation is never
achieved.

19. • An increase in temperature worsens the problems of oxygen delivery
in poikilothermic aquatic animals such as fishes.
• A rise in temperature not only reduces oxygen solubility in water but
also decreases the oxygen affinity of hemoglobin, making oxygen
transfer between water and blood more difficult.
• Differences in the properties of hemoglobins are due to variation in
the amino acid sequence of the globin portion of the molecule, the
heme portion being the same in all hemoglobins.

20. • Not only do hemoglobins vary among species, but they also may change
during development.
• In humans, for example, human fetal hemoglobin, which contains γ
chains, rather than adult β chains, has a higher O2 affinity than adult
hemoglobin.
• The higher O2 affinity of fetal hemoglobin enhances oxygen transfer from
mother to fetus.
• As the proportion of fetal hemoglobin decreases and adult hemoglobin
increases following birth, the oxygen affinity of the blood decreases.
• Other mammals exhibit similar differences between fetal and adult
hemoglobins.