PathwayStep924 PathwayStep925 PathwayStep923 PathwayStep927 PathwayStep926 PathwayStep933 PathwayStep934 PathwayStep935 PathwayStep936 Glucose transport Authored: 2003-02-15 00:00:00 Cells take up glucose by facilitated diffusion, via glucose transporters (GLUTs) associated with the plasma membrane, a reversible reaction (Joost and Thorens 2001). Four tissue-specific GLUT isoforms are known. Glucose in the cytosol is phosphorylated by tissue-specific kinases to yield glucose 6-phosphate, which cannot cross the plasma membrane because of its negative charge. In the liver, this reaction is catalyzed by glucokinase which has a low affinity for glucose (Km about 10 mM) but is not inhibited by glucose 6-phosphate. In other tissues, this reaction is catalyzed by isoforms of hexokinase. Hexokinases are feedback-inhibited by glucose 6-phosphate and have a high affinity for glucose (Km about 0.1 mM). Liver cells can thus accumulate large amounts of glucose 6-phosphate but only when blood glucose concentrations are high, while most other tissues can take up glucose even when blood glucose concentrations are low but cannot accumulate much intracellular glucose 6-phosphate. These differences are consistent with the view that that the liver functions to buffer blood glucose concentrations, while most other tissues take up glucose to meet immediate metabolic needs.<p>Glucose 6-phosphatase, expressed in liver and kidney, allows glucose 6-phosphate generated by gluconeogenesis (both tissues) and glycogen breakdown (liver) to leave the cell. The absence of glucose 6-phosphatase from other tissues makes glucose uptake by these tissues essentially irreversible, consistent with the view that cells in these tissues take up glucose for local metabolic use. GENE ONTOLOGYGO:0015758 Pubmed11780753 Reactome Database ID Release 4370153 Reactome, http://www.reactome.org ReactomeREACT_212 Regulation of Glucokinase by Glucokinase Regulatory Protein Glucose is secreted across the plasma membrane alpha-D-Glucose + ATP => alpha-D-glucose 6-phosphate + ADP transport of cytosolic alpha-D-glucose 6-phosphate into the endoplasmic reticulum alpha-D-Glucose 6-phosphate + H2O => alpha-D-Glucose + Orthophosphate GLUT1 + ATP <=> GLUT1:ATP GLUT1:ATP <=> GLUT1 + ATP alpha-D-glucose (extracellular) <=> alpha-D-glucose (cytosol) Efflux of glucose from the endoplasmic reticulum