• metabolism
  • In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. (wikipedia.org)
  • GKRP binds and moves glucokinase (GK), thereby controlling both activity and intracellular location of this key enzyme of glucose metabolism. (wikipedia.org)
  • However, with the exception of adenosine nucleotides ( Theobald et al , 1997 ) and central carbon metabolism intermediates ( Visser et al , 2004 ), little is known about the fast changes at metabolome level occurring within the first minutes following the addition of excess glucose. (embopress.org)
  • protein
  • The latter catalyzes the formation and degradation of fructose-2,6-bisphosphate (fructose-2,6-P 2 ) and is a glucokinase-binding protein. (physiology.org)
  • The monomers of the bifunctional protein are clearly divided into two functional domains. (wikipedia.org)
  • via Protein Phosphatase and PFK2, insulin increases [F-2,6-BP], which activates glycolysis by allosteric activation of PFK1, signalling an abundance of glucose PFK2 is likely to catalyze the "simple" transfer of γ-phosphoryl group of ATP onto the hydroxyl present on C-2 of fructose-6-phosphate. (wikipedia.org)
  • Five mammalian isozymes of the protein have been reported to date, difference rising by either the transcription of different enzymes or alternative splicing.The isozymes differ radically in their regulation and the discussions above are based on liver isozyme. (wikipedia.org)
  • However, variant forms of GCKR have been found to be associated with small differences in levels of glucose, insulin, triglycerides, C-reactive protein, and higher or lower risks for type 2 diabetes mellitus. (wikipedia.org)
  • glucokinase
  • The insulin-resistant Zucker fa/fa rat has elevated hepatic glycolysis and activities of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 (PFK2). (physiology.org)
  • However, combined overexpression of glucokinase and PFK2 had a synergistic effect on fructose-2,6-P 2 levels, suggesting that interaction of these enzymes may be a prerequisite for formation of fructose-2,6-P 2 . (physiology.org)
  • 8 ) showed that PFK2 binds to glucokinase through the bisphosphatase domain. (physiology.org)
  • Glucokinase has a lower affinity for glucose than the other hexokinases do, and its activity is localized to a few cell types, leaving the other three hexokinases as more important preparers of glucose for glycolysis and glycogen synthesis for most tissues and organs. (wikipedia.org)
  • The common name, glucokinase, is derived from its relative specificity for glucose under physiologic conditions. (wikipedia.org)
  • Therefore, the general glucokinase reaction is more accurately described as: Hexose + MgATP2− → hexose-PO2− 3 + MgADP− + H+ Among the hexose substrates are mannose, fructose, and glucosamine, but the affinity of glucokinase for these requires concentrations not found in cells for significant activity. (wikipedia.org)
  • Two important kinetic properties distinguish glucokinase from the other hexokinases, allowing it to function in a special role as glucose sensor. (wikipedia.org)
  • Glucokinase has a lower affinity for glucose than the other hexokinases. (wikipedia.org)
  • Glucokinase changes conformation and/or function in parallel with rising glucose concentrations in the physiologically important range of 4-10 mmol/L (72-180 mg/dl). (wikipedia.org)
  • Glucokinase is not inhibited by its product, glucose-6-phosphate. (wikipedia.org)
  • Another distinctive property of glucokinase is its moderate cooperativity with glucose, with a Hill coefficient (nH) of about 1.7. (wikipedia.org)
  • Because of this cooperativity, the kinetic interaction of glucokinase with glucose does not follow classical Michaelis-Menten kinetics. (wikipedia.org)
  • GKRP was discovered by Emile van Schaftingen and reported in 1989 Glucokinase (GK) in liver cells phosphorylates glucose, preparing it for incorporation into glycogen. (wikipedia.org)
  • hexose
  • Alternative names for this enzyme are: human hexokinase IV, hexokinase D, and ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1 (previously 2.7.1.2). (wikipedia.org)
  • gene
  • This acceleration of mRNA decay can be interpreted both as an additional nucleotide salvage pathway and an additional level of glucose‐induced regulation of gene expression. (embopress.org)
  • metabolite
  • Metabolic control analysis was used to determine enzyme coefficients on glycolysis and metabolite concentrations. (physiology.org)
  • Within the first 5 min after a sudden relief from glucose limitation, Saccharomyces cerevisiae exhibited fast changes of intracellular metabolite levels and a major transcriptional reprogramming. (embopress.org)
  • At the metabolite level, a severe drop of the AXP pools directly after glucose addition was not accompanied by any of the other three NXP. (embopress.org)
  • PFK2
  • however, like PFK2, it had a relative modest effect on the fructose-2,6-P 2 content. (physiology.org)
  • Finally, N-terminal region modulates PFK2 and FBPase2 activities, and stabilizes the dimer form of the enzyme. (wikipedia.org)
  • increases
  • Having an increased level of GLUT1, in the case of hypoxic tumors, increases the flux of glucose into the cells allowing for a higher rate of glycolysis and thus greater risks of metastasis (as elaborated upon below). (wikipedia.org)
  • The contribution of Cori cycle lactate to overall glucose production increases with fasting duration. (wikipedia.org)
  • binds
  • Fructose 6-phosphate binds to the same site of GKRP, but enhances the ability of GKRP to bind and inactivate GK. (wikipedia.org)
  • hydrolysis
  • The hydrolysis of fructose 2,6-biphosphate is likely to follow the below steps: Histidine acts as a nucleophile and attacks the 2-phosphate of F-2,6-BP The stabilization of pentacoordinated transition state by several salt bridges and hydrogen bonding. (wikipedia.org)
  • insulin
  • As a phosphoprotein phosphatase, insulin dephosphorylates the enzyme, thus activating the PFK-2 and inhibiting the FBPase-2 activities. (wikipedia.org)
  • Phosphofructokinase‐2 (PFK‐2), a central regulator of cardiac glycolysis that is normally activated in response to adrenergic stimulation and/or insulin signaling, is decreased in mouse models of reduced insulin signaling, including type 1 diabetes mellitus, high‐fat feeding, and overnight fasting. (ahajournals.org)
  • Insulin allows glucose to be taken up and used by insulin-dependent tissues. (wikipedia.org)
  • 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. (wikipedia.org)
  • pyruvate
  • For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. (wikipedia.org)
  • Lactate is transported back to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate dehydrogenase. (wikipedia.org)
  • Despite these findings, it is considered unlikely that the 2-carbon acetyl-CoA derived from the oxidation of fatty acids would produce a net yield of glucose via the citric acid cycle - however, acetyl-CoA can be converted into pyruvate and lactate through the ketogenic pathway. (wikipedia.org)
  • pathway
  • Hypoglycolytic RA T cells diverted glucose toward the pentose phosphate pathway, generated more NADPH, and consumed intracellular reactive oxygen species (ROS). (rupress.org)
  • diabetes
  • Although this may be beneficial in the fasted state to conserve systemic glucose, it represents a pathological impairment in diabetes mellitus. (ahajournals.org)
  • levels
  • 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. (wikipedia.org)
  • mechanisms
  • Yet, the formation of fructose 2,6-bisphosphate could theoretically occur by a variety of mechanisms, including the intermediary formation of Fructose-6-phosphate 2-pyrophosphate. (wikipedia.org)
  • Activation of PGI through proposed HIF-1 induced mechanisms results in increased conversion of glucose 6-phosphate to fructose 6-phosphate and also contributes to cell motility and invasion during cancer metastasis. (wikipedia.org)
  • PFKFB3
  • PFKFB3 silencing and overexpression identified a novel extraglycolytic role of the enzyme in autophagy regulation. (rupress.org)
  • convert
  • Study leader Dr. Almut Schulze, said: "Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. (wikipedia.org)
  • activity
  • The nature of the cooperativity has been postulated to involve a "slow transition" between two different enzyme states with different rates of activity. (wikipedia.org)