Glucose 6-phosphate dephosphorylation in gluconeogenesis

Glucose 6-phosphate hydrolysis by glucose 6-phosphatase bypasses the irreversible hexokinase/glucokinase reaction and provides an energetically favorable pathway for the formation of free glucose (Fig. 1). The liver is the primary organ that produces free glucose from glucose 6-phosphate.

This process requires a complex of two proteins found only in gluconeogenic tissue: glucose 6-phosphate translocase, which transports glucose 6-phosphate across the endoplasmic reticular (ER) membrane, and glucose 6-phosphatase, which removes the phosphate, producing free glucose (see Fig. 1). [Note: These ER membrane proteins are also required for the final step of glycogen degradation . Glycogen storage diseases Ia and Ib, caused by deficiencies in the phosphatase and the translocase, respectively, are characterized by severe fasting hypoglycemia, because free glucose is unable to be produced from either gluconeogenesis or glycogenolysis.] Specific transporters are responsible for moving the free glucose into the cytosol and then into blood.

Figure 1: Dephosphorylation of glucose 6-phosphate allows release of free glucose from gluconeogenic tissues (primarily the liver) into blood. = phosphate.