What is haemoglobin?
The hemoglobin are red globular proteins, which have a molecular weight of about 68,000 and comprise almost one third of the weight of a red cell. The haemoglobin composed of haem and globin.
Haemoglobin Synthesis
¨ The main function of red cells is to carry O2 to the tissues and to return carbon dioxide (CO2) from tissues to the lungs. the red cells contain the specialized protein haemoglobin helps to achieve this gaseous exchange. Approximately 640 million Hb molecules are found in each red cell.¨Haem synthesis occurs largely in the mitochondria and globin synthesis occurs in the polyribosomes. ¨65% of the Hb is synthesized in the erythroblasts, and 35% at the reticulocyte stage. Haem and globin synthesis seperately.
Each molecule of normal adult haemoglobin (Hb-A) consists of four polypeptide chains a2b2, each with its own haem group
Globin Synthesis
Various globin that combine with haem to form Hb are all single chain polypeptides. Genetic control synthesis these globin. Humans normally carry eight functional globin chains, arranged in two, duplicated gene clusters: the b-like cluster (b, g, d and e globin genes) on the short arm of chromosome 11 and the a-like cluster (a and z globin genes) on the short arm of chromosome 16.
2. Haem synthesis
Haem synthesis starts with the condensation of glycine and succinyl coenzyme A under the action of a rate limiting enzyme d-aminolaevulinic acid synthase. Next, d-ALA will be formed and
Pyridoxal phosphate (vitamin B6) is a coenzyme for this reaction.
A series of biochemical reactions will follow. Two molecules of d-ALA condense to form a pyrrole called porphobilinogen (PBG). Then, four PBG condense to form a tetrapyrrole uroporphyrinogen III. UPG III is then converted to coproporphyrinogen. UPG III is then converted to coproporphyrinogen.
¨CPG then changes to protoporphyrin which ultimately combines with iron in the ferrous state (Fe2+) to form haem. Iron is brought to the developing red cells by a carrier protein called transferrin which attaches to special binding sites on the surface of these cells. Transferrin releases iron and returns back to circulation.
Each molecule of haem combines with a globin chain. At the end, the tetramer of four globin chains each with its own haem group in a pocket is formed to make up a haemoglobin molecule.
Haemoglobin catabolism
¨Red cell destruction usually occurs after a mean life span of 120 days. The cells are expelled extravascularly by reticuloendothelial system (RES) macrophages, which are found mostly in the bone marrow but also in the liver and spleen. The metabolism of red blood cells deteriorates over time as enzymes are destroyed and not replaced, until the cells are no longer viable, although the exact cause for red cell death is unknown.
The break down of the normal red blood cell:
1- Iron for recirculation via plasma transferrin to marrow erythroblasts
2- Protoporphyrin is broken down to bilirubin.
3- Globins which are converted to amino acids.
The bilirubin circulates to the liver where it is conjugated to glucuronides which are excreted into the gut via bile and converted to stercobilinogen and stercobilin which excreted in faeces. Stercobilinogen and stercobilin are partly reabsorbed and excreted in urine as urobilinogen and urobilin.
A small fraction of protoporphyrin is converted to carbon monoxide (CO) and excreted via the lungs.
¨Globin chains are broken down to amino acids which are reutilized for general protein synthesis in the body.
References
Abdulmalik O, Safo MK, Lerner NB et al. (2004) Characterization of hemoglobin bassett (alpha94Asp → Ala), a variant with very low oxygen affinity. Am J Hematol 77:268–276. 10.1002/ajh.20184 [PubMed] [CrossRef] [Google Scholar]
Abdulmalik O, Safo MK, Chen Q et al. (2005) 5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells. Br J Haematol 128:552–561. 10.1111/j.1365-2141.2004.05332.x [PubMed] [CrossRef] [Google Scholar]
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