What does glucokinase regulatory protein do?
The glucokinase regulatory protein (GKRP) also known as glucokinase (hexokinase 4) regulator (GCKR) is a protein produced in hepatocytes (liver cells). GKRP binds and moves glucokinase (GK), thereby controlling both activity and intracellular location of this key enzyme of glucose metabolism.
What regulates glucokinase?
Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by GK regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP.
What happens when glucokinase is inhibited?
Inhibition of glucokinase abolishes the ventromedial nucleus response to a meal. However, brain glucose levels are lower than plasma levels, typically 0.5–3.5 mmol/L. Although this range is matches the sensitivity of the glucose-sensing neurons, it is below the optimal inflection sensitivity for glucokinase.
Why is glucokinase regulated by f6p?
In the presence of fructose 6-phosphate, the regulatory protein binds to, and inhibits, liver glucokinase. Both phosphate esters act by binding to the regulatory protein, and by presumably causing changes in its conformation. The regulatory protein behaves as a fully competitive inhibitor.
What is the role of glucokinase?
Glucokinase is an enzyme responsible for the conversion of glucose into glucose-6 phosphate and plays a central role as a glucose sensor in the regulation of glucose homeostasis. Accordingly, agents that cause activation of glucokinase have potential for the treatment of type 2 diabetes (T2D).
Why does glucokinase have a low affinity for glucose?
Due to regulation by GCKR, glucokinase in intact liver cells has a lower affinity for glucose than does the purified enzyme, and low concentrations of fructose stimulate glucose utilization by the liver (Agius, 2016; Van Schaftingen et al., 1994).
Does glucagon inhibit glucokinase?
Glucagon inhibits glucose-induced glucokinase translocation and glucose phosphorylation.
How is glucokinase inhibited?
Glucokinase is inhibited in the postabsorptive state by sequestration in the nucleus bound to GKRP, and it is activated postprandially by portal hyperglycemia and fructose through dissociation from GKRP, translocation to the cytoplasm, and binding to PFK2/FBP2.
How is glucokinase regulated in the liver?
Glucokinase expression is transcriptionally regulated by hormones and metabolites of glucose, and glucokinase activity is dependent on reversible binding of glucokinase to a specific inhibitor protein, glucokinase regulatory protein (GKRP), and to other binding proteins such as 6-phosphofructo-2-kinase/fructose 2,6- …
Is glucokinase a glucose sensor?
It is hypothesized that glucokinase (GCK) is the glucose sensor not only for regulation of insulin release by pancreatic β-cells, but also for the rest of the cells that contribute to glucose homeostasis in mammals.
How does glycogenesis affect blood glucose levels?
glycogenesis, the formation of glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, from glucose. Glycogenesis takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells. Glycogenesis is stimulated by the hormone insulin.