Pathways targeted by PK(s) activators and l-glutamine in red cells. The glycolytic pathway generates ATP and interfaces the pentose phosphate shunt, which is the main source of reduced nicotinamide adenine dinucleotide phosphate (NADPH). This is required by antioxidant systems and the Rapoport-Luebering shunt that generates 2,3-DPG. PK is the last enzyme in the glycolytic pathway. In SCD, the intense and sustain oxidation results in consumption of NADH and glutathione, favoring hemolysis. l-Glutamine as glutamate might support NADH and GSH systems, reducing red cell oxidation. ADP, adenosine diphosphate; GSH, glutathione; NADP, NAD phosphate.