Anemias pentose phosphate pathway

The pentose phosphate pathway is operative in the RBC (it metabolizes about 5-10% of the total flux of glucose) and produces NADPH hemolytic anemia due to a deficiency of the activity of glucose-6-phosphate dehydrogenase is common. 

Deficiency of the first enzyme of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase, is widespread.11 Its geographical distribution suggests that, like the sickle-cell trait, it confers some resistance to malaria. A partial deficiency of 6-phosphogluconolactonase (Eq. 17-12, step b) has also been detected within a family and may have contributed to the observed hemolytic anemia.1... 

Cells differ considerably in their use of the pentose f phosphate pathway. In muscle, a tissue in which carbohydrates are utilized almost exclusively for generation of mechanical energy, the enzymes of the pentose phosphate pathway are lacking. By contrast, red blood cells are totally dependent on the pentose phosphate pathway as a source of NADPH for which they need to keep the iron of hemoglobin in its normal +2 valence state. A deficiency in glucose-6-phosphate dehydrogenase, the first enzyme in the pentose phosphate pathway, can lead to the wholesale destruction of red blood cells and a condition known as hemolytic anemia. 

The pentose phosphate pathway is the only source of NADPH in red blood cells, which, as a result, are highly dependent on the proper functioning of the enzymes involved. A glucose-6-phosphate dehydrogenase deficiency leads to an NADPH deficiency, which can, in turn, lead to hemolytic anemia because of wholesale destruction of red blood cells. 

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