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CRRM1.4: HAEMOGLOBIN 30/10/07 LEARNING OUTCOMES Describe and explain the carriage of O2 by haemoglobin, including an outline of the molecular changes involved Haemoglobin is composed of four protein molecules interacting in a quaternary structure: two alpha chains and two beta chains Each polypeptide chain contains a haem group (complex organic ring structure called a porphyrin) to which up to four ferrous iron (Fe2+) can bind Each ferrous iron atom can bind an O2 molecule to form oxyhaemoglobin The typical adult form of haemoglobin is HbA; in the foetus it is HbF which instead of two beta chains has two gamma chains which convert at birth Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin so that it can ‘steal’ oxygen from maternal blood Explain the changes in binding of oxygen by haemoglobin due to different physiological factors As oxygen molecules bind to the ferrous iron sites, the porphyrin ring relaxes and increases affinity of the remaining sites for further O2 binding As oxygen molecules are released, the beta chains rotate and a 2,3-BPG molecule binds centrally, stabilising the tensile conformation and reducing its affinity for O 2 binding As well as oxygen and carbon dioxide haemoglobin can also bind H+ ions which reduce affinity for O2 binding; therefore acid pH e.g. in respiring muscles causes increased O2 release Describe changes in haemoglobin in disease Haemoglobinopathies are inherited diseases in which there are abnormalities in haemoglobin They are the most common serious inherited diseases worldwide Sickle cell anaemia is a recessive autosomal disorder in which a point mutation results in a single amino acid substitution of glutamine for valine (loss of negative charge) The haemoglobin molecules formed are of the type HbS which form long crystals – ‘sickle’ shapes HbS molecules have reduced membrane flexibility, become ‘dehydrated’ and dense, which results in their being easily clogged up in narrow vessels and reduced stability in the oxygenated state Sickle cell anaemia has a high incidence in Africans (1 in 4 carry the gene) Thalassaemias are characterised by inadequate quantities of the protein haemoglobin subunits and occur in two forms: o α-thalassaemia is often caused by gene deletions on the α-chain genes from the mother and father; if all four genes are deleted then no α-chains are expressed and the haemoglobin cannot function resulting in hydrops fetalis and stillbirth o β-thalassaemia is where β-chain production is reduced resulting in excess α-chains In both cases the thalassaemias result in ineffective or reduced erythropoiesis from haemolysis Describe and explain the carriage of CO2 by the blood