GCKR
Description
The GCKR (glucokinase regulator) is a protein-coding gene located on chromosome 2.
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. GKRP is a 68 kD protein of 626 amino acids. It is coded for by a 19 exon gene, GCKR, on the short arm of chromosome 2 (2p23). GKRP was discovered by Emile van Schaftingen and reported in 1989
== Physiological function == Glucokinase (GK) in liver cells phosphorylates glucose, preparing it for incorporation into glycogen or for glycolysis. During periods of ample glucose supply, most GK activity can be found in the peripheral cytoplasm where glycogen synthesis is occurring. As the glucose supply declines during periods of fasting, GK activity in the cytoplasm diminishes. GKRP participates in this modulation of GK activity and location by binding free cytoplasmic GK as glucose levels decline, and moving it into the nucleus, where it is held in reserve in an inactive form. As glucose and insulin levels rise, as during digestion of a meal, GK is released from GKRP and moves back to the cytoplasm, where much of it associates with the bifunctional enzyme. In hepatocytes of various mammals, GKRP has always been found in molar excess of the amount of GK, but the GKRP:GK ratio varies according to diet, insulin sufficiency, and other factors.
GCKR regulates glucokinase (GCK) activity by forming an inactive complex with it. This regulation involves GCKR promoting GCK's translocation to the nucleus, potentially serving as a reservoir for rapid GCK release into the cytoplasm following a meal. The binding affinity of GCKR for GCK is influenced by fructose metabolites. GCKR with bound fructose 6-phosphate exhibits enhanced affinity for GCK, whereas GCKR bound to fructose 1-phosphate displays significantly reduced affinity for GCK, consequently failing to inhibit GCK activity.
GCKR is also known as FGQTL5, GKRP.
