PathwayStep929 PathwayStep928 PathwayStep930 PathwayStep931 PathwayStep932 Regulation of Glucokinase by Glucokinase Regulatory Protein Edited: D'Eustachio, P, 2006-02-20 18:39:56 GENE ONTOLOGYGO:0010827 Glucokinase (GCK1) is negatively regulated by glucokinase regulatory protein (GKRP), which reversibly binds the enzyme to form an inactive complex. Binding is stimulated by fructose 6-phosphate and sorbitol 6-phosphate (hence high concentrations of these molecules tend to reduce GCK1 activity) and inhibited by fructose 1-phosphate (hence a high concentration of this molecule tends to increase GCK1 activity). Once formed, the complex is translocated to the nucleus. In the presence of high glucose concentrations, the nuclear GCK1:GKRP complex dissociates, freeing GCK1 to return to the cytosol. The free GKRP is thought also to return to the cytosol under these conditions, but this return has not been confirmed experimentally. Possible physiological roles for this sequestration process are to decrease futile cycling between glucose and glucose 6 phosphate in hepatocytes under low-glucose conditions, and to decrease the lag between a rise in intracellular glucose levels and the onset of glucose phosphorylation in both hepatocytes and pancreatic beta cells (Brocklehurst et al. 2004; Shiota et al. 1999). Pubmed10601273 Pubmed14627435 Reactome Database ID Release 43170822 Reactome, http://www.reactome.org ReactomeREACT_6804 cytosolic GCK1:GKRP complex <=> glucokinase (GCK1) + glucokinase regulatory protein (GKRP) GCK1:GKRP [cytosol] => GCK1:GKRP [nucleoplasm] glucokinase (GCK1) + glucokinase regulatory protein (GKRP) <=> GCK1:GKRP complex Dissociation of the nucleoplasmic GCK1:GKRP complex glucokinase [nucleoplasm] => glucokinase [cytosol]