By Jennifer McDowall


Link to the structural features of haemoglobin


            When we breathe in oxygen, the red blood cells transport it around to every cell in the body – a critical process that has far-reaching evolutionary consequences.  The advent of aerobic respiration, which added the oxygen-utilising tricarboxylic acid cycle and electron transport system onto anaerobic glycolysis, allowed aerobic organisms to extract 18 times more energy from glucose in the form of ATP.  Initially, organisms relied on diffusion to transport oxygen to their cells, an inefficient system that kept them microscopic in size.  Then with the development of the body cavity came a primitive circulatory system involving the flow of interstitial fluid through the action of muscular movement; yet, body size remained small, as this system of circulation was limited in its effectiveness.  Nematode worms have a primitive type of body cavity (pseudocoelom) and circulation; these tiny animals consist of just under a 1000 cells and as such are barely visible with the naked eye.  With the advent of a true circulatory system to transport highly specialised red blood cells close to every cell in the body no matter how large the organism, so that oxygen could now reach all cells, body size was able to expand radically up to the largest animal to currently inhabit the earth: the blue whale, which can weight up to 150 tons and stretch 100 feet in length from head to tail. 


Haemoglobin, an Oxygen Carrier



Red blood cells


            A drop of blood contains millions of red blood cells, or erythrocytes.   These specialised cells are like flattened discs, which gives them a much greater surface area with which to exchange oxygen and carbon dioxide in the lungs and with body cells.  Red blood cells are able to carry oxygen so efficiently because of a special protein inside them: haemoglobin.  In fact, it is the haemoglobin that is responsible for the colour of the red blood cell.  Haemoglobin contains a haem prosthetic group that has an iron atom at its centre.  When the iron is bound to oxygen, the haem group is red in colour (oxyhameoglobin), and when it lacks oxygen (deoxygenated form) it is blue-red.  As blood passes through the lungs, the haemoglobin picks up oxygen because of the increased oxygen pressure in the capillaries of the lungs, and can then release this oxygen to body cells where the oxygen pressure in the tissues is lower.  In addition, the red blood cells can pick up the waste product, carbon dioxide, some of which is carried by the haemoglobin (at a different site from where it carries the oxygen), while the rest is dissolved in the plasma.  The high carbon dioxide levels in the tissues lowers the pH, and the binding of haemoglobin to carbon dioxide causes a conformational change that facilitates the release of oxygen.  The carbon dioxide is then released once the red blood cells reach the lungs.

            Haemoglobin is composed of four polypeptide chains, which in adults consist of two alpha (a) globin chains and two beta (b) globin chains (i.e. a2b2).  Each polypeptide has a haem prosthetic group attached, where each haem can bind one oxygen molecule - so there are four haem groups per haemoglobin molecule that together bind four oxygen molecules. 


Foetal Haemoglobin, in a Class of its Own


            The foetus has different haemoglobin needs from that of an adult.  The foetus receives its blood supply via the umbilical vein from the placenta.  However, by the time the blood has reached the placenta, much of its oxygen has already been used up by the mother.  Consequently, foetal haemoglobin needs to be able to bind oxygen with a higher affinity than maternal blood, if enough oxygen is to reach the foetus.  Initially, embryonic haemoglobin is the main form, consisting of at least three types: Gower1 (zeta2 epsilon2, or z2e2), Gower2 (alpha2 epsilon2, or a2e2), and Portland (zeta2 gamma2, or z2g2).  The z and e globin chains are unique to embryonic haemoglobin and appear to be synthesised almost entirely in the yolk sac.

After the second month of development, the foetus switches to foetal haemoglobin (haemoglobin F; alpha2 gamma2, or a2g2).  At birth, approximately 50-95% of the child’s haemoglobin is foetal haemoglobin, but after six months, these levels decline and adult haemoglobin (haemoglobin A, a2b2) becomes the predominant form, as it is better suited to the oxygen transport requirements after birth.  There is also haemoglobin A2 (alpha2 delta2, or a2d2), which is synthesised late in the third trimester and continues into adulthood at a level of 2.5%. 


Haemoglobin and High Altitudes


            People living at high altitudes, such as in the Tibetan Plateau or the Andes Mountains, have developed unique and often different ways to cope with the reduced amount of oxygen available at higher altitudes.  Natives of the Andes Mountains in South America have a higher concentration of haemoglobin in their blood, allowing more oxygen to be carried by the same volume of blood.  However, there are other means of coping with high altitudes.  For instance, the people living in the Tibetan Plateau have doubled their nitric oxide levels.  Nitric oxide is a blood vessel dilator, which is thought to boost the uptake of oxygen.


Next:  Haemoglobin and Disease