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Mini MCAT passage: Pentose phosphate pathway and G6DP deficiency


Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency affects more than 400 million people across the globe and is the most common enzyme abnormality in humans that results in disease. Many of the disease manifestations are the result of the inability to produce NADPH in the Pentose Phosphate Pathway (PPP). NADPH has many roles in the cell, but one important role is in the maintenance of reduced glutathione, which is an anti-oxidant in the cell. The intimate reduction-oxidation relationship between NADPH and reduced glutathione is shown in Figure 1.
Figure 1 Pathways of G6P and glutathione metabolism in cells
Reduced glutathione helps keep many important cellular proteins in their normal, reduced forms, protecting cells from oxidants like reactive oxygen species (ROS). This is particularly important in red blood cells (RBCs), as oxidation of protein groups in hemoglobin causes these proteins to form insoluble and denatured masses that target RBCs for premature removal from the blood. This can result in anemia, or a low RBC count, in some G6PD deficient patients.
Image Attribution: Springler-Verla, ISSN 1432-1076
What would you expect to happen to fatty acid synthesis in patients with G6PD deficiency?
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