Mini Review - Insights in Nutrition and Metabolism (2022) Volume 6, Issue 4
Glucose metabolism, breakdown and its regulation in liverAmena Rukhsar*
Department of Biochemistry, Faculty of Science, Agriculture & Engineering, Newcastle University, United Kingdom
- *Corresponding Author:
- Amena Rukhsar
Department of Biochemistry
Faculty of Science, Agriculture & Engineering
Newcastle University, United Kingdom
Received: 30-Jun-2022, Manuscript No. AAINM-22-68167; Editor assigned: 02-Jul-2022, PreQC No. AAINM-22-68167(PQ); Reviewed: 16-July-2022, QC No. AAINM-22-68167; Revised: 21-Jul-2022, Manuscript No. AAINM-22-68167(R); Published: 28-Jul-2022, DOI:10.35841/aainm-6.4.117
Citation: Rukhsar A. Glucose metabolism, breakdown and its regulation in liver. Insights Nutr Metab. 2022;6(4):117
Glucose homeostasis is firmly regulated to meet the energy prerequisites of the vital organs and keep an individual's health. The liver plays a significant part in the control of glucose homeostasis by controlling different pathways of glucose metabolism, including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis. Both the acute and chronic guideline of the proteins associated with the pathways are expected for the legitimate working of these complex interlaced systems.
Glucose homeostasis, Glycogenesis, Glycogenolysis, Glycolysis.
Outline of glucose metabolism in the liver
Depriving conditions, dietary carbohydrates are processed and digested by different glucosidases in the gastrointestinal system, and the resultant monosaccharides, predominantly hexose glucose, are moved into different tissues as an essential fuel for ATP age. In most mammalian tissues, the catabolism of glucose into pyruvate, named glycolysis, is safeguarded as a significant pathway in evoking ATP . In tissues with bountiful mitochondria, cytosolic pyruvate is moved into the mitochondrial network, changed over completely to Acetyl- CoA by pyruvate dehydrogenase complex, and integrated into the Krebs cycle related to oxaloacetate. The cycle creates energy identical to ATP (that is, GTP) as well as both NADH and FADH2, which act as significant electron transporters for electron transport chain-oxidative phosphorylation, bringing about the age of ATP.
Under fasting conditions, the liver plays a significant part in producing glucose as a fuel for different tissues, like the mind, red blood cells and muscles. At first, an expansion in the pancreatic chemical glucagon starts the outpouring of kinase activity (expressed underneath exhaustively) that sets glucose free from the put away glycogen by means of glycogenolysis . Normally, put away glycogen is basic for keeping up with glucose homeostasis in well evolved creatures during a short-term fasting period. During a more extended term quick or starvation, basically the put away glycogen in the liver is all drained (after ~30 h of fasting), and once more glucose combination or gluconeogenesis is liable for the age of glucose as a fuel for different tissues. Major non-carbohydrate antecedents for gluconeogenesis are lactate, which is moved from fringe tissues like skeletal muscles or red blood cells, and glycerol, which is let out of the fat tissues through improved lipolysis during fasting. A large portion of the underlying precursors for gluconeogenesis are produced in the mitochondria (with the exception of glycerol 3-phosphate through glycerol kinase action), however most of the response happens in the cytosolic part of the cell.
Regulation of glycogen metabolism in the liver
The accumulation of glycogen in the liver during feeding conditions gives a storage type of glucose that can be utilized in the midst of diminished food consumption. Numerous layers of regulation are expected for this cycle for both the activation of glycogen synthase, which is a main enzyme of glycogenesis (glycogen blend), and the inhibition of glycogen phosphorylase, which is a vital enzyme of glycogenolysis (glycogen breakdown) in the liver. Glycogen synthase is a significant catalyst that works with the lengthening of glycogen chains by catalyzing the transfer of the glucose residue of UDP-glucose to the non-reducing end of a previous glycogen branch to deliver a new α1→4 glycosidic linkage. The regulation of glycogen synthase has been generally concentrated on utilizing a muscle-explicit isoform. In the muscle, glycogen synthase is inactivated by means of phosphorylation on numerous serine residues by different serine/threonine kinases, for example, casein kinase-1, protein kinase A (PKA), and glycogen synthase kinase-3 (GSK-3). Most remarkably, the phosphorylation of glycogen synthase by GSK-3 at serine residues 640, 644 and 648 has been connected to the main inhibitory post-translational adjustment for its catalytic activity .
Under fasting conditions, dephosphorylated and dynamic GSK-3 phosphorylate and inactivate glycogen synthase, prompting the hindrance of hepatic glycogen combination. On taking care of, expanded insulin flagging enacts Akt in the cell, which thus phosphorylates and inactivates GSK-3, hence bringing about the actuation of glycogen synthase. Likewise, expanded convergences of glucose 6-phosphate allosterically initiate this compound, along these lines potentiating its reactant movement depriving conditions . The protein phosphatase 1 (PP1) might be liable for the dephosphorylation and actuation of glycogen synthase. As needs be, both glucose and insulin have been displayed to actuate PP1 action, while glucagon and epinephrine have been connected to the hindrance of its action.
Glycogen phosphorylase is a significant protein engaged with glycogenolysis. This enzyme catalyzes the reaction of the removal of a glucose residue from the non-reducing end of a glycogen chain, generation of glucose 1-phosphate. Glucose 1-phosphate can be changed over into glucose 6-phosphate by phosphoglucomutase, and glucose 6-phosphate can be integrated into glycolysis or further changed over into glucose by glucose 6-phosphatase, contingent upon the energy status of the creature. Glycogen phosphorylase is dynamic when it is phosphorylated at its serine 14 residue. The phosphorylation of glycogen phosphorylase requires an outpouring system of epinephrine and glucagon in the liver. On the enactment of Gαs by the limiting of chemicals to cell surface G protein-coupled receptors (beta adrenergic receptor or glucagon receptor), the intracellular cyclic AMP (cAMP) levels increase through adenylate cyclase, prompting the initiation of PKA . PKA is then responsible for the phosphorylation and activation of glycogen phosphorylase kinase, which thus phosphorylates and initiates glycogen phosphorylase to improve glycogen breakdown. In depriving conditions, this kinase cascade is dormant because of the absence of discharge of catabolic hormones. Also, insulin advances the initiation of PP1, which dephosphorylates and inactivates glycogen phosphorylase. Basically, the anabolic chemical insulin advances glycogenesis and inhibits glycogenolysis by means of the activation of PP1, leading the dephosphorylation of glycogen phosphorylase (inactivation) and glycogen synthase (activation), and through the initiation of Akt, leading the phosphorylation of GSK-3 (inactivation) that can't phosphorylate and inactivate glycogen synthase.
- Ros S, García-Rocha M, Domínguez J, et al. Control of liver glycogen synthase activity and intracellular distribution by phosphorylation. J Biol Chem. 2009;284(10):6370-8.
- Roach PJ. Glycogen and its metabolism. Curr Mol Med. 2002;2(2):101-20.
- van de Werve G, Jeanrenaud B. Liver glycogen metabolism: An overview. Diabetes Metab Rev. 1987;3(1):47-78.
- Agius L. Role of glycogen phosphorylase in liver glycogen metabolism. Mol Aspects Med. 2015;46:34-45.
- Erion DM, Ignatova ID, Yonemitsu S, et al. Prevention of hepatic steatosis and hepatic insulin resistance by knockdown of cAMP response element-binding protein. Cell Metab. 2009;10(6):499-506.