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Bacterial glycogen synthesis and its regulation

Hojlund K, Birk JB, Klein DK, et al:Dysregulation of glycogen synthase COOH- andNH2-terminal phosphorylation by insulin in obesity andtype 2 diabetes mellitus. J Clin Endocrinol Metab. 94:4547–4556.2009. :

Glycogen synthesis is, unlike its breakdown, endergonic—it requires the input of energy

103. Zamek-Gliszczynski MJ, Abraham TL, Alberts JJ, Kulanthaivel P, Jackson KA, Chow KH. . Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure. 2013;41:714-26

Regulation of Glycogen Synthesis and Degradation

While the exact contribution of each of these factors is unknown, they may act in combination to stimulate rapid muscle glycogen re synthesis rates.

GSK-3, glycogen synthase kinase-3; nM, nanomolar; ATP, adenosine triphosphate; GS, glycogen synthase; PI-3 kinase, phosphatidylinositol-4, 5-bisphosphate 3-kinase; PKB, protein kinase B; BD, bipolar disorder; AD, Alzheimer's disease; Wnt pathway, a pathway that transfers signals from the outside of the cell to the inside of the cell through cell surface receptors; β-catenin, cadherin association protein; KDa, kilodalton; IC50, the half maximal inhibitory concentration; SAR, structure activity relationship; HBD, hydrogen bond donor; HBA, hydrogen bond acceptor; PBMC, peripheral blood mononuclear cells; AIDS, acquired immunodeficiency syndrome; Pgp, P-glycoprotein; PET, positron emission tomography; MDR-MDCK assay, a permeability assay using Madin-Darby canine kidney cells with the gene; CDK1, cyclin-dependent kinase 1; ERK2, extracellular signal-regulated kinase 2, also known as mitogen activated protein kinase; IL-8, interleukin 8; ZDF, Zucker diabetic fatty; PIM1, proto-oncogene serine/threonine-protein kinase; PAK1, serine/threonine-protein kinase 1; DAPK1, death-associated protein kinase 1; MLCK, myosin light-chain kinase; FLT4, fms-related tyrosine kinase 4; CK2, casein kinase-II; CLK1, dual specificity protein kinase; PD, Parkinson's disease; HD, Huntington's disease; CNS, central nervous system; TMED, threshold minimum effective dose; TDZD, Thiadiazolidinones; PKA, protein kinase A; PKC, protein kinase C; PSP, progressive supranuclear palsy; MMSE, mini-mental status examination, cGMP, current Good Manufacturing Practice; and ITDZ, 5-imino-1, 2, 4-thiadiazole.

GSK-3 is involved in a large number of key cellular processes and exhibits dysregulation in a wide variety of disease states. Accordingly, modulation of GSK-3 activity has been deemed an important approach for therapy and imaging. As shown in this limited review, a very large number of GSK-3 inhibitors have been synthesized. However, as reflected in the slow progress of these inhibitors toward clinical translation, a number of challenges remain. Adverse effects caused by off-target activity of GSK-3 inhibitors were determined after the screening of compounds that bind to the ATP-competitive binding site conserved across a broad range of kinases. Therefore, it would be extremely advantageous to design and develop GSK-3 inhibitors that can selectively target individual pathways and differentiate between the phosphorylated and non-phosphorylated forms of GSK-3. In this regard, parallel development of a therapeutic molecule with a closely related imaging biomarker may allow early evaluation of drug candidates based on noninvasive imaging measurements of the target-to-background ratios. Imaging can also be instrumental in defining the brain uptake patterns of GSK inhibitors intended for brain-related disorders, which would allow for the early dismissal of candidates that show poor brain penetration or retention. Alternative approaches to ligand design may be needed to improve GSK-3 targeting specificity for both therapy and imaging purposes.

Glycogen: Biosynthesis and Regulation. - Abstract - …

2. Summers SA, Kao AW, Kohn AD, Backus GS, Roth RA, Pessin JE. . The role of glycogen synthase kinase 3beta in insulin-stimulated glucose metabolism. 1999;274:17934-40

Gebhardt et al.[] showed application of emodin (82) and its ethylenediamine analog 83 as non-ATP competitive inhibitors of GSK-3 (Table ). Addition of the ethylenediamine group on the emodin nucleus increased potency of inhibition (IC50 0.56±0.02 µM, 83), reduced cytotoxicity and generated an insulin sensitizing effect mediated by increasing hepatocellular glycogen and fatty acid biosynthesis. Selectivity's of compounds 82 and 83 were evaluated against twelve protein kinases including eleven of human protein kinases. Compound 83 showed high selectivity towards GSK-3β but 82 failed to do so.

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16/10/2016 · Glycogen: Biosynthesis and Regulation

Bouskila M, Hirshman MF, Jensen J,Goodyear LJ and Sakamoto K: Insulin promotes glycogen synthesis inthe absence of GSK3 phosphorylation in skeletal muscle. Am JPhysiol Endocrinol Metab. 294:E28–E35. 2008. :

REGULATION OF GLYCOGEN METABOLISM - …

Bai G, Zhang ZJ, Werner R, Nuttall FQ, TanAW and Lee EY: The primary structure of rat liver glycogen synthasededuced by cDNA cloning. Absence of phosphorylation sites 1a and1b. J Biol Chem. 265:7843–7848. 1990.

Glycogenesis is the process of glycogen synthesis, ..

9. Montori-Grau M, Tarrats N, Osorio-Conles O, Orozco A, Serrano-Marco L, Vazquez-Carrera M. . Glucose dependence of glycogen synthase activity regulation by GSK3 and MEK/ERK inhibitors and angiotensin-(1-7) action on these pathways in cultured human myotubes. 2013;25:1318-27

regulation of muscle glycogen synthase and the ..

A weight gain of more that 1 or 2 pounds will indicate that you are over correcting your water losses and may be placing yourself at risk for this unusual metabolic condition.Question: I am a fairly strong Cat 4 rider that wants to moveup to Cat 3 and wanted to get some feedback on whether or not I shouldpursue a protein/carbohydrate recovery drink mix like Endurox R4/Acceleradeto help aid recovery and restore my glycogen levels.

been considered to control the rate of glycogen synthesis.

52. Dong J, Peng J, Zhang H, Mondesire WH, Jian W, Mills GB. . Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity. 2005;65:1961-72

f Impaired glycogen synthesis causes metabolic …

"...re-synthesis after short term, high intensity exercise (15.1 to 33.6 mmol/kg/h) is much higher than glycogen re-synthesis rates following prolonged exercise (approximately 2 mmol/kg/h), even when optimal amounts of oral carbohydrate are supplied (approximately mmol/kg/h)." My take on this article, and the fast food, more liberal repletion concept?

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