In the red blood cells of glucose-6-phosphate dehydrogenase deficient subjects, structural changes will occur during oxidative stress owing to disulphides build up. In turn this causes haemoglobins to denature and precipitate as lumpy particles known as Heinz bodies which attach to the cell membrane and alter its charge, elasticity and permeability. When the oxidative damage to the cell membrane by disulphide formation is not repaired, the cell is marked as abnormal and removed by the reticuloendothelial system i.e. the spleen, liver and bone marrow, thus initiating a haemolytic anaemia. 1. 4. 7. 10.Subjects with the African type deficiency where the reticulocytes and younger erythrocytes retain about 10% of residual glucose-6-phosphate dehydrogenase activity are usually asymptomatic until exposed to oxidative stress. The episodes of haemolysis are usually brief because newly produced red cells often have activity comparable to normal glucose-6-phosphate dehydrogenase. Those with the Mediterranean type on the other hand have a reduced glucose-6-phosphate dehydrogenase activity even in the young cells and may suffer from more serious haemolytic episodes. 1. 3. 11.
It has been established that primaquine's mode of cell damage is by acting as an electron donor to oxygen which is bound in the elemental form to haemoglobin iron. The iron in the ferrous state can provide only one electron to the bound oxygen therefore avoiding the formation of free radicals and peroxide. Primaquine cause oxidative damage in the red blood cell by donating the second electron which accelerates the oxidative process 1.and increasing the activity of membrane ATPase. The hydrolysis of ATP will induce morphological changes in red blood cells. 12. 13.
Although the same glucose-6-phosphate dehydrogenase gene is expressed in all tissues in the body, the effect of the deficiency in the red blood cell is most severe probably because of their long non-nucleated life span which means that the enzyme synthesised in the red blood cells when still nucleated while in the bone marrow must serve for the life span of the cells. The lack of mitochondria makes glucose-6-phosphate dehydrogenase oxidative shunt the only source of NADPH in the red blood cells. Furthermore, there is a possibility that red blood cells contain proteases which are more likely than proteases of other tissues to degrade mutant glucose-6-phosphate dehydrogenase enzymes. 1. 3.
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Prepared on 01 Jan 2008 by teekoonhien |
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