Overview Function generate NADPH required for FA synthesis, steroid synthesis, reduction of oxidizing agents (H2O2 see figure) provide ribose 5-phosphate required for nucleotide synthesis Pathway occurs in cytoplasm of all cells no ATP consumed or generated 2 phases oxidative produces NADPH glucose 6-phosphate (G6P) → 6-phosphogluconate catalyzed by glucose 6-phosphate dehydrogenase (G6PDH) rate limiting step activated by NADP+, insulin inhibited by NADPH irreversible nonoxidative exchanging intermediate substrates between glycolysis and HMP shunt catalyzed by transketolase requires thiamine reversible Clinical relevance glucose-6-phosphate dehydrogenase (G6PDH) deficiency pathophysiology ↓ NADPH production cells (specifically RBCs) lose protection against oxidizing agents cannot regenerate glutathione XR most common human enzyme deficiency ↑ prevalence among blacks ↑ malarial resistance by shortening the circulation life of RBCs Plasmodium does not have enough time for life span plasmodium does not have defense against free radicals ↑ in free radicals kills parasite presentation episodic hemolytic anemia intravascular hemolysis normocytic 2-3 days post precipitating stress foods fava beans common in Mediterranean foods presentation pallor, hemoglobinuria 24-48 post ingestion drugs sulfonamides, primaquine, antituberculosis drugs infection free radicals generated by the immune system Heinz bodies oxidized hemoglobin that precipitates within RBCs bite cells result from the phagocytic removal of Heinz bodies by macrophages back pain test active hemolysis screen Heinz body prep