Glucokinase (GCK, hexokinase IV) is a monomeric enzyme that catalyzes the ATP-dependent conversion of glucose to glucose 6-phosphate, the first and rate-limiting step of glycolysis in the liver and pancreas. In humans, GCK is primarily produced in pancreatic β-cells and liver hepatoparenchymal cells. Within pancreatic β-cells, GCK acts to maintain glucose homeostasis by governing the rate of insulin secretion, while in the liver GCK participates in glycogen synthesis. GCK regulation is complex and a number of unique regulatory strategies have been discovered. Alternative and tissue-specific promoters drive GCK transcription and gene expression to varying degrees. Phosphofructokinase-2/fructose bisphosphatase-2 (PFK-2/FBPase- 2) is an enzyme responsible for the synthesis and degradation of fructose-2,6-bisphosphate, an important allosteric regulator of glycolysis and gluconeogenesis. . As PFK-2/FBPase-2 is expressed in both liver hepatocytes and pancreatic β-cells, it contributes to GCK regulation in both organs. GCK resides in a mitochondrial-associated complex contains BCL 2-associated death promoter (BAD), protein kinase A (PKA, cAMP-dependent protein kinase), protein phosphatase 1 (PP1, dual-specificity serine/threonine phosphatase), and Wiskott-Aldrich family member (WAVE1). GCK is also subject to a number of protein-protein interactions and post-translational modification events that produce a broad range of physiological consequences.

References

1.Sternisha SM,et al. Arch Biochem Biophys. 2019;663:199–213.