Glucose-6-Phosphate Dehydrogenase deficiency

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency affects more than $400$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). Recall that the other major byproduct of the PPP is ribose-5-phosphate. 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 G6PD and Glutathione Metabolism in Cells. Note that the enzymes that catalyze reactions are boxed. The rest of the molecules listed are substrates for these enzymes. *

Of note, reduced glutathione helps keep many important cellular proteins in their normal, reduced forms and essentially protects cells from “oxidants” like reactive oxygen species (i.e. oxygen molecule that has gained extra electron(s)). This is particularly important in red blood cells (RBCs). Oxidation of protein groups in hemoglobin causes these proteins to form insoluble and denatured masses that target these 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