**2. Liver glucose metabolism**

After a meal rich in carbohydrates, high levels of glucose reach the liver via portal vein. Glucose enters passively the hepatocyte through GLUT-2, a facilitated glucose transporter, and then is rapidly phosphorylated by GK at the sixth carbon to obtain glucose-6-phosphate which cannot escape the cell. From a functional perspective, it is important to recognize that both GLUT2 and glucokinase are expressed in cell types in which glucose metabolism has to vary accordingly to extracellular glucose concentration (glucose sensors). The high Km for glucose of both proteins, and the absence of product inhibition by glucose-6-phosphate, ensure that glucose uptake and phosphorylation in these cells are proportional to extracellular glucose concentration throughout the physiological range of glycaemia

The product of GK reaction, glucose-6-phosphate, is the gateway to the major pathways of glucose utilization: glycogen synthesis, glycolysis, oxidation of glucose and pentose phosphate pathway. It should be noted that hepatic glycolysis provides pyruvate principally for lipid synthesis rather than for oxidation. As glucose is the main substrate for fatty acid synthesis, hepatic glycolytic enzymes can be considered an extension of the lipogenic pathway. Glucose, insulin and parasympathetic nervous system orchestrate these glucose metabolic pathways in the fed state, with the aim of maintaining normal levels of blood sugar.
