Regulation of Glycogen Synthesis

Glycogen Metabolism (Danio rerio) - WikiPathways

Glycogen metabolism (Homo sapiens) - WikiPathways

The reaction is highly regulated by allosteric effectors such as , by phosphorylation reactions, and indirectly triggered by the hormone , which is secreted by the . Phosphorylation of glycogen synthase decreases its activity. The enzyme also cleaves the ester bond between the C1 position of glucose and the of UDP itself.

Glycogen metabolism (Homo sapiens) From WikiPathways

Glycogen Metabolism (Pan troglodytes) - WikiPathways

Exercise stimulates muscle glucose uptake both directly and by increasing the sensitivity of this process to insulin. Increased fat intake and intracellular triglycerides may cause insulin resistance and hamper muscle glycogen resynthesis. According to one study, exercise increased insulin sensitivity in normal subjects because of a two fold increase in insulin-stimulated glycogen synthesis in muscle, due to an increase in insulin-stimulated glucose transport-phosphorylation . Since insulin sensitivity is highest after resistance exercise, it is vital to take a high glycemic index drink immediately after training. This stimulates the secretion of insulin to allow rapid muscle glycogen resynthesis. The general formula is to consume about 1.5 grams of high glycemic index carbohydrates per kilogram of bodyweight after weight training. Glycogen restoration rate is higher following glucose feeding as compared with fructose feeding because of glucose's higher glycemic index rating. Some people have mentioned to me that protein is also needed along with carbohydrates to increase muscle glycogen resynthesis. I believe if you consume a high glycemic index carbohydrate after training at the amount given above, then additional protein will not improve muscle glycogen resynthesis . If you are on a ketogenic type of a diet than consuming certain amino acids (namely branched chain) may allow for an insulin response causing an increase in muscle glycogen resynthesis. By the way, supercompensated muscle glycogen levels can maintained at least three days after carb loading on a moderate carbohydrate diet according to a study at the .

Glycogen Metabolism (Canis familiaris) - WikiPathways

glycogen appears to function as an immediate reserve source of available glucose for muscle cells. Other cells that contain small amounts use it locally as well. Muscle cells lack the enzyme , which is required to pass glucose into the blood, so the glycogen they store is destined for internal use and is not shared with other cells. (This is in contrast to liver cells which, on demand, readily do break down their stored glycogen into glucose and send it through the blood stream as fuel for the or muscles). Glycogen is also a suitable storage substance due to its insolubility in water, which means it does not affect the osmotistic levels and pressure of a cell.

Glycogen Metabolism (Bos taurus) - WikiPathways


the key regulatory enzyme of glycogen synthesis.

There are two mammalian GSK3 isoforms encoded by distinct genes: GSK3-Alpha and GSK3-Beta. GSK3-Beta is particularly abundant in the CNS (Central Nervous System) and directly phosphorylates several neuronal MAPs (Microtubule-Associated Proteins), involved in microtubule stabilization (Ref.3). GSK3 is negatively regulated by of PI3K (Phosphatidylinositol 3-Kinase)-mediated activation of Akt/PKB (Protein Kinase-B) and by the WNT signaling pathway (Ref.5). In the absence of a WNT signal, GSK3 is a part of the multiprotein complex that includes the proteins AXIN (Axis Inhibitor), APC (Adenomatous Polyposis Coli), CSNK1 (Casein Kinase-1) and Beta-Ctnn (Beta-Catenin) which is localized at the membrane along with the Cadherins. These proteins help GSK3 to efficiently phosphorylate the signaling molecule Beta-Ctnn, thus targeting it for ubiquitination and subsequent proteosomal degradation. AXIN acts as a scaffolding protein in this complex, binding both GSK3 and Beta-Ctnn in a manner that brings them into close proximity, thus allowing GSK3 to phosphorylate Beta-Ctnn. AXIN therefore acts as a GSK3 activating protein. When GSK3 is active, it phosphorylates APC and Beta-Ctnn and stimulates interaction between Beta-Ctnn and Beta-TRCP (Beta-Transducin Repeat-Containing Protein), a regulator of E3 Ubiquitin Lligase, which degrades Beta-Ctnn in proteasomes (Ref.4 & 10). GSK3 phosphorylates a variety of substrates, other than Beta-Ctnn such as Glycogen Synthase and other metabolic enzymes, transcription factors CBP (CREB Binding Protein), c-Myc and c-Jun, and the translation initiation factors eIF2 and eIF2B (Ref.6). Phosphorylation of transcription factors by GSK3-Beta causes ubiquitination, nuclear exit, or decreases in the DNA binding, leading to decrease in nuclear transcription (Ref.4). In neuronal cells, GSK3 phosphorylate a number of MAPs, such as MAP2C, MAP1B and Tau. Phosphorylation of these proteins by GSK3 decreases their ability to stabilize microtubules (Ref.7). Binding of the WNT molecules to Fz (Frizzled) receptors activates Dsh (Dishevelled) through G-proteins G-AlphaQ and G-AlphaO, which inhibits the activity of GSK3, thereby stabilizing Beta-Ctnn. CSNKI (Casein Kinase-I) also makes a complex with AXIN, GSK3 and Dsh and works as a positive regulator of the WNT signaling. Stabilization of Beta-Ctnn is associated with its translocation to the nucleus in presence of PP2A (Protein Phosphatase-2A) where it interacts with members of the LEF (Lymphoid Enhancer Factor)/ TCF (T-Cell Factor) and activates specific target genes (Ref.4). When Beta-Ctnn is absent, certain TCFs repress transcription by interacting with the corepressors TLE (Transducin-Like Enhancer) and CTBP (C-Terminal Binding Protein). Another GSK3 interacting molecule, GBP (GSK3 Binding Protein), and its mammalian homologue FRAT (Frequently Rearranged in Advanced T-Cell Lymphomas), binds to GSK3 and inhibits its phosphorylation of non-primed GSK3 substrates, including Beta-Ctnn. GBP/FRAT compete with AXIN for binding to GSK3, resulting in GSK3 inhibition (Ref.2). Numerous other stimuli also lead to inactivation of GSK3, including Growth Factors such as EGF (Epidermal Growth Factor) and PDGF (Platelet-Derived Growth Factor) that stimulate the GSK3-inactivating kinase p90RSK (also known as MAPKAPK1) through RasGTP-MAPK (Mitogen Activated Protein Kinase), activators of p70S6K (p70 Ribosomal S6 Kinase) such as amino acids, activators of cAMP-activated PKA (Protein Kinase-A) (Ref.1). GSK3 induce Caspase3 activation and activate the proapoptotic tumor suppressor gene, p53. It also promotes activation and translocation of the proapoptotic BCL2 (B-cell Lymphomal Leukaemia) family member, BAX (BCL2 Associated X-protein), which, upon aggregation and mitochondrial localization, induces CytoC (Cytochrome-C) release. Akt is one of the critical regulators of GSK3, and phosphorylation and inactivation of GSK3 may mediate some of the antiapoptotic effects of Akt (Ref.9).

Glycogen; Pentose phosphate pathway;

There have only been two comprehensive studies , that have investigated muscle glycogen synthesis after resistance exercise. Pascoe et al reported a 31% decrease in muscle glycogen levels after resistance training. Robergs et al reported muscle glycogen degradations of about 38% after resistance training. Muscle glycogen resynthesis after resistance exercise (weight lifting) is considerably faster than prolonged aerobic exercise . Eccentric exercise has been associated with ultrastructural muscle damage, leakage of intracellular enzymes, delayed onset muscle soreness , AND reduced rates of glycogen resynthesis ,. Some evidence suggests that the anti-inflammatory cells which enter muscle tissue in response to the eccentrically induced damage compete with the muscle cells for available plasma glucose . In addition, these inflammatory cells may produce a metabolic factor that shifts muscle metabolism towards glycogenolysis (glycogen breakdown) and away from glycogen synthesis. It is speculated that the damage resulting form eccentric exercise interfered with the insertion of the GLUT 4 protein into the plasma membrane and increased the rate of degradation or the rate of production of this glucose transporter protein . The evidence sited above shows that eccentric contractions and subsequent muscle damage impair muscle glycogen resynthesis. I would recommend more explosive, concentric type of movements to enhance glycogen resynthesis after resistance training. This would especially be necessary while carbohydrate loading/depleting (before a bodybuilding competition for example). The recruitment of more fast twitch glycolytic muscle fibers may also enhance glycogen synthesis .