2. Glucose Transport
After the breakdown of dietary polysaccharides, glucose, fructose and galactose are taken up by enterocytes lining the microvilli of the small intestine. GLUT5 on the lumenal surface of the small intestine mediates fructose uptake. Sodium-dependent glucose cotransporters (members of the sodium-glucose cotransporter (SGLT) protein family) mediate the uptake of glucose and galactose. GLUT2 on the basolateral surface of enterocytes facilitates the release of hexoses into the circulatory system for reuptake by other cells [11]. When monosaccharide levels are high, GLUT2 may facilitate hexose uptake from the gut lumen [12]. In hepatocytes and other somatic cells, GLUT5 mediates fructose uptake from the circulatory system. Phosphorylation by tissue-specific kinases converts cytosolic glucose to glucose-6-phosphate (G6P). The negative charge on G6P prevents it from crossing the cell membrane. Glucokinase, which has a low affinity for glucose and is not inhibited by G6P, catalyzes this reaction in hepatocytes. When blood glucose concentrations are high, hepatocytes may accumulate G6P to buffer glucose concentrations. Glucose-6-phosphatase allows G6P from gluconeogenesis and glycogen breakdown to exit liver and kidney cells. Hexokinase isoforms, which have a high affinity for glucose and are feedback inhibited by G6P, catalyze the reaction of glucose to G6P in other body tissues. Those tissues can take up glucose during times when blood glucose concentrations are low. However, they are not able to accumulate high levels of G6P. The absence of glucose-6-phosphatase makes glucose uptake irreversible in those tissues [13,14].