Glucokinase

Glucokinase EC 2. Glucokinase occurs in cells glucokinase the liver and glucokinase of humans and most other vertebrates, glucokinase. 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, glucokinase, such as occur after a meal or when fasting.

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.

Glucokinase

Federal government websites often end in. The site is secure. Glucose transport is by facilitated diffusion and is not rate limiting. Once inside, glucose is phosphorylated to glucosephosphate by GCK in a reaction that is dependent on glucose throughout the physiological range of concentrations, is irreversible, and not product inhibited. High glycerol phosphate shuttle, pyruvate dehydrogenase, and pyruvate carboxylase activities, combined with low pentose-P shunt, lactate dehydrogenase, plasma membrane monocarboxylate transport, and glycogen synthase activities constrain glucosephosphate to being metabolized through glycolysis. Under these conditions, glycolysis produces mostly pyruvate and little lactate. Pyruvate either enters the citric acid cycle through pyruvate dehydrogenase or is carboxylated by pyruvate carboxylase. Reducing equivalents from glycolysis enter oxidative phosphorylation through both the glycerol phosphate shuttle and citric acid cycle. Specific roles of different cell types are determined by the diverse molecular mechanisms used to couple energy state to cell specific responses. Having a common glucose sensor couples complementary regulatory mechanisms into a tightly regulated and stable glucose homeostatic network. Our hypothesis is that glucokinase GCK is the primary glucose sensor in mammals and the sensor responsible for regulation of glucose homeostasis as schematically represented in Figure 1.

Kawamori, D. Publish with us For authors Language editing services Submit manuscript. In addition, the reaction products themselves may activate or inhibit metabolism not directly related to that glucokinase the original metabolite, 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.

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. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively.

Glucokinase

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.

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The supply of G6P affects the rate of glycogen synthesis not only as the primary substrate, but by direct stimulation of glycogen synthase and inhibition of glycogen phosphorylase. It is important to define metabolite sensing and sensors. Tools Tools. Both inhibitors lower the rate of glucose metabolism 42 , 43 , 44 , which would explain that normally inhibitory 4 mM glucose acts as a stimulator of glucagon secretion. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Figure 4. Supplementary Information. Molecular physiology of mammalian glucokinase. Skip to main content Thank you for visiting nature. Physiology 22 , — Provided by the Springer Nature SharedIt content-sharing initiative. However, as would be expected given its antagonistic effect on glycogen synthesis, glucagon and its intracellular second messenger cAMP suppresses glucokinase transcription and activity, even in the presence of insulin. Radiometric oil well assay for glucokinase in microscopic structures. What do we know after 50 years?

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. None of the funders had any role in the study design. Glucokinase activity was manipulated by acute treatment with either 0. Read Edit View history. Brain glucose sensing, counterregulation, and energy homeostasis. Thorens, B. Neuron 38 , — EC number Enzyme superfamily Enzyme family List of enzymes. Raising blood glucose of mice was observed to profoundly change the metabolite and cofactor profiles in the pancreatic islets. The pentose cycle and insulin release in mouse pancreatic islets. Pyruvate carboxylase Phosphoenolpyruvate carboxykinase.