Download Transport of Oxygen

Transport of Oxygen
Hemoglobin and Oxygen Association
Adult humans require about 250 ml of new oxygen to enter the bloodstream per
minute to support the internal respiration of their tissues while in a relaxed state.
Since oxygen is poorly soluble in our plasma, we only deliver about 15 ml of
oxygen per minute to our tissues in dissolved form (0.3 ml of dissolved oxygen
per deciliter of blood times 50 deciliters (a unit that refers to 10 mls of a liquid)
per minute of cardiac output. Therefore we become critically dependent on
another mechanism to help deliver sufficient amounts of oxygen to where it is
needed. That mechanism utilizes a protein, hemoglobin as a transporter
molecule for either oxygen or carbon dioxide. Red blood cells contain high
concentrations of hemoglobin.
In order to be able to discuss the different macromolecules and the reactions
they undergo, it is important to be familiar with the common chemical symbols
that are used.
Here are a few of symbols you will see:
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Deoxyhemoglobin (HHb) - A hemoglobin molecule that has been reduced
and does not have a full complement of oxygen molecules attached to it.
Oxygen (O2) - A gas that is required for converting nutrients into cellular
energy.
Oxyhemoglobin (HbO2)- A hemoglobin molecule that has been oxidized and
is bound to four oxygen molecules.
Carbon dioxide (CO2) - A gas that is released as a waste product during the
breakdown of glucose to release energy.
2,3-bisphosphoglycerate (BPG) - is a molecule found in red blood cells that
can bind to hemoglobin and decrease its affinity for oxygen.
Carbonic acid ( H2CO3 ) - is formed as an intermediate step in the
transportation of carbon dioxide. Carbonic anhydrase is an enzyme that will
speed up the formation of carbonic acid from water and carbon dioxide.
Bicarbonate (HCO3−) - Carbonic acid can quickly convert to bicarbonate and
a hydrogen ion. Bicarbonate plays a huge role in transporting carbon dioxide
and maintaining blood pH.
On this curve, the x axis lists the PO2 of the blood (whether it is in the lungs or
other body tissues), and the y axis lists the percent saturation of the hemoglobin
with oxygen. This graph has a sigmoidal ‘S’ shape, such that changes in partial
pressures above 80 mmHg do not have a major effect on the percent of
hemoglobin saturation. Since normal partial pressure in the lungs is over 100
mmHg, there are some safety factors that are important for people who travel to
altitude or develop ventilation disorders to consider. As long as neither is too
severe, hemoglobin will stay close to 100% saturated as long as the partial
pressure in the alveoli can stay above 80 mmHg. Under normal conditions,
hemoglobin ends up nearly 100% saturated in the lungs and then travels to the
tissues. In the tissues, hemoglobin will have given up 25% of the oxygen it
carries such that it is now 75% saturated (the relationship between oxygen levels
and partial pressure is not linear because of the shape of the curve). If there is a
higher demand for oxygen in metabolically active cells, more of the oxygen will
diffuse into the tissues reducing hemoglobin saturation below 75%.
Hemoglobin and Oxygen Dissociation
Tight binding of oxygen to hemoglobin allows us to transport oxygen throughout
our cardiovascular system. At the same time hemoglobin cannot bind oxygen so
tightly that oxygen cannot leave the hemoglobin when it the molecule encounters
oxygen deprived tissues. Metabolically active tissues cause local environmental
changes making it easier for oxygen to unload from hemoglobin in these tissues.
These changes in rates of dissociation can be visualized by looking at
the oxygen-hemoglobin dissociation under different conditions such as
changing temperature, PCO2, pH, and the levels of 2,3-bisphosphoglycerate
(BPG). Increased cellular metabolism causes increases in temperature, BPG
production and carbon dioxide levels. The increased carbon dioxide further
causes a decrease pH. When this happens, oxygen more readily leaves
hemoglobin molecules, and the oxygen-hemoglobin dissociation curve is shifted
to the right. Regulation of oxygen delivery to cells is important since cells with a
high metabolic rate need more oxygen to produce ATP.
Specifically, the oxygen-hemoglobin bond is weakened in the more acidic
environment, and the oxygen leaves the heme more readily. The most commonly
found acids that result in a locally lowered pH include lactic acid and carbonic
acid. Lactic acid production results from situations where there is inadequate
oxygen supply and cells have shifted to anaerobic metabolism of glucose for
energy production. Carbonic acid is formed when carbon dioxide dissolves in
water. Since carbon dioxide production is a byproduct of aerobic metabolism, it
follows that very metabolically active cells will exhibit increased levels of carbon
dioxide production. The chemical equation linking the increased carbon dioxide
to a lowering of pH is CO2 + H2O ↔ H2CO3 ↔ H++HCO3 which we will discuss
later.
Red bloods metabolize glucose in a variation of the standard glycolysis pathway.
BPG is an intermediate compound made in red blood cells during glycolysis.
When present in red blood cells, it attaches to the terminal amino acid groups of
hemoglobin’s beta chains and decreases the affinity of hemoglobin for oxygen.
BPG will increase in response to endocrine regulators including thyroxine,
epinephrine, norepinephrine, and testosterone, and as part of the compensation
that occurs at high altitudes and with some anemias.