A patient of Mediterranean ancestry was given primaquine to protect against malaria when going on an overseas trip. The patient rapidly developed a hemolytic anemia due to a mostly silent mutation in which one of the following pathways or enzymes?
The patient most likely has glucose-6-phosphate dehydrogenase deficiency, one of the enzymes that produces NADPH. When glucose-6-phosphate dehydrogenase is defective, both it and the subsequent enzyme in the hexose monophosphate shunt pathway (6-phosphogluconate dehydrogenase) do not produce NADPH. The red blood cells have insufficient NADPH; under these conditions, to keep glutathione in its reduced, protective form, and in the presence of a strong oxidizing agent (primaquine), red cell membrane damage occurs, and the cells lyse, producing the hemolytic anemia. Mutations in glycolysis, gluconeogenesis, and fatty acid oxidation do not fit this pattern of damage in the presence of a strong oxidizing agent. Mutations in glycolysis (such as pyruvate kinase) can lead to anemia, but that occurs in the absence of oxidizing agents as well. The red blood cells do not oxidize fatty acids, nor do they carry out gluconeogenesis.
Malic enzyme
Glycolysis
Hexose monophosphate shunt
Gluconeogenesis
Endocrinology