Glucokinase

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Glucokinase EC 2. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. 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. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia. Glucokinase GK is a hexokinase isozyme , related homologously to at least three other hexokinases.

Glucokinase

Official websites use. Share sensitive information only on official, secure websites. The GCK gene provides instructions for making a protein called glucokinase. This protein plays an important role in the breakdown of sugars particularly glucose in the body. Glucokinase is primarily found in the liver and in beta cells in the pancreas. Beta cells produce and release secrete the hormone insulin, which helps regulate blood glucose levels by controlling how much glucose is passed from the bloodstream into cells to be used as energy. Glucokinase acts as a sensor, recognizing when the level of glucose in the blood rises and helping stimulate the release of insulin from beta cells to control it. In the liver, glucokinase helps determine when excess glucose should be taken in and converted to glycogen, which is a major source of stored energy in the body. Mutations in the GCK gene cause maturity-onset diabetes of the young MODY , which is a group of conditions characterized by abnormally high blood glucose levels. This form of diabetes usually begins before age Affected individuals usually have mildly elevated blood glucose levels from birth, although they typically have no symptoms associated with the condition, and diabetes-related complications are extremely rare. The altered protein may be broken down, or the function may be impaired, reducing glucokinase activity in cells. As a result, beta cells are less able to detect changes in blood glucose and release insulin to control it, so blood glucose remains elevated. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Study of human diseases linked to genetic alterations in GCK, glucokinase, together with pharmacological studies using GKAs, glucokinase, have led to discovery that GCK has a hitherto unrecognized allosteric activator site see Figure glucokinase. Glucokinase Glucokinase is a hexokinase isozymerelated homologously to at least three other hexokinases. Oxidative phosphorylation: unique regulatory mechanism and role in metabolic homeostasis.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: 1 do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and 2 is glucokinase the alpha cell glucose sensor in this scenario.

Glucose metabolism in humans is tightly controlled by the activity of glucokinase GCK. GCK is predominantly produced in the pancreas, where it catalyzes the rate-limiting step of insulin secretion, and in the liver, where it participates in glycogen synthesis. A multitude of disease-causing mutations within the gck gene have been identified. Activating mutations manifest themselves in the clinic as congenital hyperinsulinism, while loss-of-function mutations produce several diabetic conditions. Indeed, pharmaceutical companies have shown great interest in developing GCK-associated treatments for diabetic patients. Due to its essential role in maintaining whole-body glucose homeostasis, GCK activity is extensively regulated at multiple levels. GCK possesses a unique ability to self-regulate its own activity via slow conformational dynamics, which allows for a cooperative response to glucose. GCK is also subject to a number of protein-protein interactions and post-translational modification events that produce a broad range of physiological consequences. While significant advances in our understanding of these individual regulatory mechanisms have been recently achieved, how these strategies are integrated and coordinated within the cell is less clear.

Glucokinase

Federal government websites often end in. The site is secure. Type 2 diabetes mellitus is a metabolic disorder with complicated pathogenesis, and mono-target therapy often fails to effectively manage the levels of blood glucose. In recent years, the anti-diabetes target glucokinase GK has attracted the attention of researchers. It acts as a glucose sensor, triggering counter regulatory responses following a change in glucose levels to aid restoration of normoglycemia. Activation of GK induces glucose metabolism and reduces glucose levels for the treatment of type 2 diabetes. GK agonists GKA are a new class of antidiabetic drugs. This article describes the mechanism of action of GK in diabetes and of action of GKA at the protein level, and provides a review of the research, trends, and prospects regarding the use of GKA in this setting. GK, termed hexokinase 4, is a member of the hexokinase family 1 , 2.

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Reissaus, C. Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics. Nissim et al. Lamy et al. About this article. What do we know after 50 years? Not everyone uses the same definitions, and giving our definitions at the outset may avoid misunderstanding due to semantic differences. Glucose at physiological concentrations facilitates enzymatic conversion of phosphorylase a to phosphorylase b and this inhibits glycogenolysis, an effect synergistic with glucose stimulation of glycogen synthesis. Human Mutation. Neuron 38 , —

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It is important to note that increase in energy state with increase in glucose concentration, through near equilibrium of adenylate kinase, also markedly decreases [AMP]. The pH optimum of human glucokinase was identified only recently and is surprisingly high, at pH 8. It is puzzling, however, that in gonadotropes of the cynomolgus monkey GCK appeared to be clearly confined to cytosolic substructures, tentatively identified as Golgi complex Sorenson et al. Download PDF. The pHluorin is co-expressed and co-packaged together with glucagon into secretory vesicles, which was verified by counterstaining with an anti-prohormone convertase 2 PC2 -antibody. Basco et al. Effect of a glucokinase activator on hepatic intermediary metabolism: study with C-isotopomer-based metabolomics. Programming and regulation of metabolic homeostasis. Oxidative phosphorylation: regulation and role in cellular and tissue metabolism. Encyclopedia of Molecular Medicine. Moreover, inhibition by glucose is not affected by inhibitors of GCK, indicating that in these particular neurons glucose sensing is not by GCK and metabolism of glucose is not required. Some biochemists have argued that the name glucokinase should be abandoned as misleading, as this enzyme can phosphorylate other hexoses in the right conditions, and there are distantly related enzymes in bacteria with more absolute specificity for glucose that better deserve the name and the EC 2. Sorry, a shareable link is not currently available for this article.