Give an account of the factors which influence the binding of oxygen to hemoglobin.

Outline:

·        How does oxygen binds to hemoglobin

·        Affinity of hemoglobin to oxygen

·        Factors involved:

- temperature

- oxygen level

- type of hemoglobin

- carbon dioxide / H⁺

- 2,3-DPG

Essay:

            More than 98% of the oxygen in a given volume of blood is transported inside the red blood cells, where it is bound to hemoglobin. A hemoglobin molecule is composed of four globin subunits (2 a and 2 b), each centered around a heme group whose central iron atom binds reversibly with an oxygen molecule.

            The amount of oxygen that can binds to hemoglobin depends on the PO₂ of the plasma surrounding the red blood cells. The quaternary structure of hemoglobin determines its affinity for oxygen; by shifting the relationship of its 4 component polypeptide chains, the molecule fosters either oxygen uptake or oxygen delivery. The movement of the chains is associated with a change in the position of the heme moieties, which assume a relaxed or R state that favors oxygen binding or a tense or T state that decreases oxygen binding. The transition of one state to another involves breaking or forming bridges between the polypeptide chains. Combination of the first heme in the Hb molecule increases the affinity of the second heme for oxygen, and oxygenation of the second increases the affinity of the third, etc. When hemoglobin takes up oxygen, the two b chains move closer together; when oxygen is given up, they move farther apart. This property of the hemoglobin molecule enables it to release oxygen with ease when the plasma PO₂  is low in the tissues and to bind oxygen diffusing in from the lung alveoli when the plasma PO₂ is high.

            The factors that influence the binding of oxygen to hemoglobin are temperature, pH, carbon dioxide, 2,3-DPG and the type of hemoglobin. An increase in temperature, fall in pH or rise in carbon dioxide levels decrease the affinity of hemoglobin to oxygen. Carbon dioxide is carried as carbamate bound to the uncharged a-amino groups of hemoglobin. The binding of carbon dioxide stabilizes the T (taut) or deoxy form of hemoglobin, resulting in a decrease in its affinity for oxygen. The deoxy form of hemoglobin has a greater affinity for protons than the oxygenated form. The protons bind to the a-amino groups and specific histidine side chains and enable them to form ionic bonds with one another. These bonds preferentially stabilize the deoxy form of hemoglobin, producing a decrease in oxygen affinity and binding.

            2,3-DPG is very plentiful in red cells. It is formed from 3-phosphoglyceraldehyde, which is a product of glycolysis via the Embden-Meyerhof pathway. It is a highly charged anion that binds to the b chains of deoxyhemoglobin. This preferential binding stabilizes the taut conformation of deoxyhemoglobin and decreases oxygen binding.

            Fetal hemoglobin is a tetramer consisting of two a chains and two g chains. The greater affinity of fetal hemoglobin than adult hemoglobin for oxygen facilitates the movement of oxygen from the mother to the fetus. The cause of this greater affinity is the poor binding of 2,3-DPG by the g polypeptide chains that replace the b chains in fetal hemoglobin.