Proposed pathways for G6P metabolism in normal and G6PC3-deficient neutrophils. Glucose transported into the cytoplasm via GLUT1 is metabolized by hexokinase to G6P which can participate in glycolysis, hexose monophosphate shunt (HMS), glycogen synthesis, or be translocated into the lumen of the ER by the G6PT. In normal neutrophils, G6P localized within the ER lumen can be hydrolyzed by G6Pase-β and the resulting glucose transported back into the cytoplasm to reenter any of the previously mentioned cytoplasmic pathways. However, in G6PC3-deficient neutrophils, which lack a functional G6Pase-β, ER-localized G6P cannot be recycled to the cytoplasm. The GLUT1 transporter, responsible for the transport of glucose in and out of the cell, is shown embedded in the plasma membrane. The G6PT, responsible for the transport of G6P into the ER and G6Pase-β, responsible for hydrolyzing G6P to glucose and phosphate, are shown embedded in the ER membrane.