Blood: A Very Short Introduction by Chris Cooper
Author:Chris Cooper [Cooper, Chris]
Language: eng
Format: epub
ISBN: 9780191665172
Publisher: Oxford University Press
Published: 2016-07-02T00:00:00+00:00
When Perutz looked at the three-dimensional structure it became clear how this process had evolved. The organic porphyrin is a planar ring structure. In the R state of haemoglobin, the iron atom at the centre of this ring sits slightly above the plane (illustrated in Figure 13). Once oxygen is bound to the iron it is energetically favourable for the atom to move down towards the plane. This movement in turn pulls amino acids near the iron towards the ring. In a kind of âmolecular dominoâ effect, a wide variety of other interactions are perturbed, including crucially those at the interface between the alpha and beta subunits. Thus an action at one of the four protein subunits can be converted into a concerted structural change that affects all of them. The R to T state change is best seen in a colour video, for example <http://biochem.web.utah.edu/iwasa/projects/hemoglobin.html>.
The haemoglobin structure enables the body to subtly and appropriately regulate its oxygen binding to suit environmental changes. As the R and T states have different structures they bind small molecules differently; as a consequence, allosteric effectors can elegantly control the oxygen affinity via preferentially binding, and hence stabilizing, the R or T states of the protein. For example, organs of the body that receive low levels of oxygen produce excess lactic acid. Elsewhere, where oxygen consumption is proceeding very quickly, a lot of carbon dioxide is produced. Both these conditions can co-exist in certain conditions such as intense exercise. In these circumstances the blood circulation needs to supply more oxygen to these tissues. In 1904 the Danish physiologist Christian Bohr discovered that under conditions of high carbon dioxide or increased acidity, haemoglobin decreases its affinity for oxygen, enabling those tissues to be preferentially targeted for enhanced oxygen delivery (Figure 15).
15. The Bohr effect. Acid and carbon dioxide facilitate oxygen offloading to tissue.
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