DOCSLIB.ORG

Cellular Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

CST SIGNALING PATHWAY DIAGRAMS FOR Cellular Metabolism Insulin Receptor Signaling © 2003–2015 Cell Signaling Technology, Inc. Insulin Receptor SNARE TNF Glucose Complex GLUT4 p85 FlotillinCav PTEN PI3K Gab1 p110 SOCS3 Synip CAP TNFR1 Cbl PIP3 IRS Shc APS SHIP Akt2 SHP-2 PTP1B GLUT4 Crkll EHD1 GRB2 Nck Translocation TC10 C3G EHBP1 IRS-1 Crkll λ/ζ CIP4/2 PKC Fyn SOS PDK1 Rac1 mTORC2 PKCθ GRB10 Jnk GLUT4 PKCλ/ζ IKK vesicle Ras PP2A FFA 14-3-3 LKB1 NO iNOS GLUT4 AS160 Exocytosis Akt ROS c-Raf TBC1D1 AMPK PDK1 14-3-3 TSC2 PDE3B TSC1 Bad SIK2 GSK-3 PRAS40 Rheb [cAMP] MEK1/2 SGK Apoptosis SREBP CBP/p300 mTORC1 PKA Torc2 p70 Erk1/2 PP1 GS Lipin1 4E-BP1 S6K ATP-citrate Degradation ENaC lyase eIF4E HSL Glycogen Synthesis Protein Synthesis, Fatty Acid Growth, and SREBP-1 Sodium Synthesis Proliferation Lipolysis Transport Cytoplasm Erk1/2 SGK Akt2 Fatty Acid and Cholesterol Disruption of Nucleus Synthesis CBP/Torc2/CREB Complex FoxO3 FoxO4 FoxO1 Erk1/2 SREBP LXRα USF Gluconeogenesis Transcription Apoptosis, mTORC1 mTORC2 Autophagy, Lipin1 Glucose and Raptor Sin1 PRR5 GβL Lipid Metabolism Growth mTOR Rictor GβL DEPTOR mTOR DEPTOR Warburg Effect © 2010–2015 Cell Signaling Technology, Inc. Macropinocytosis and other scavenging pathways Glycolysis Growth Factors Glucose Glucose Transporters Ras Hexokinase PI3K Amino Acids NADPH NADP Ras Pentose and Lipids c-Myc Phosphate 6-P- Glucose-6-P Akt Shunt Gluconolactone 6-P- MEK1/2 NADP Ras Amino Acids Gluconate TIGAR Fructose-6-P NADPH p53 LKB1 SREBP PFK Erk1/2 Ribulose-5P AMPK Fructose mTOR Bisphosphate Nucleotide c-Myc HIF-1α Synthesis PHGDH Serine 3-Phosphoglycerate Protein Synthesis Cell Proliferation NADPH c-Myc NADP Glycine PEP ULK1 PKM2 HIF-1α Fatty Acid Oxidation NADP c-Myc Pyruvate Autophagy Fatty Acids NADPH Malic Enzyme LDHA Pyruvate PDHK Lactate Dehydrogenase Malate Pyruvate Acetyl-CoA Folate β Metabolism Oxaloacetate -Oxidation Acetate Bax Akt ANT Krebs Malate Cycle Citrate Citrate ACSS2 Hexokinase VDAC ACL ANT UCP2 IDH2 AMPK Acetyl-CoA VDAC α-Ketoglutarate IDH1 ACC OMM Stability Fatty Acid/ NADP Inhibition Cytochrome C Release Glutaminase Lipid Synthesis Inhibition of Apoptosis NADPH Epigenetic p53 Glutamine Transporters Regulation Glutamine AMPK Signaling Glutaminolysis © 2008–2015 Cell Signaling Technology, Inc. Low Glucose, Hypoxia, Ischemia, Heat Shock Brain AICAR Insulin Leptin Exercise α-Adrenergic Histamine Other RTKs Receptor Adiponectin Receptor Thrombin Glucose Receptor Glut1 Insulin Glut4 PLCβ Gα q [cAMP] AMP + ADP ATP Glut1 vesicle PKA Ras [Ca2+] PI3K Glut Glut Translocation STRAD B-Raf Trafficking CaMKK LKB1 MO25α Glut4 vesicle TXNIP Erk Akt A c u t Glycogen TBC1D1 e GS p90RSK γ R Synthesis β e g u TSC2 l Glycolysis PFKFB3 α a AMPK y t g i o TSC1 Rheb a n h HMG-CoA p o o f t Sterol/Isoprenoid Reductase M ACC Raptor u e Synthesis A t β d a Malonyl mTOR G L b n CoA a o l i CPT1 s m m s i ULK1 4E-BP1 l Fatty Acid p70 o b a Oxidation HSL FIP200 ATG13 S6K t e Autophagy M n i e p300 t Beclin o r ATGL SREBP-1 P PI3K Lipolysis Atg14 MYPT1 Class III Tau MBS85 HNF4α SirT1 HDAC4 Fatty Acid CLIP170 Synthase HDAC5 Microtubules Lipogenesis HDAC7 TORC2/ Myosin CRTC2 C Light yt Chain2 os ke PGC1α m le Actin lis ta o l S Dynamics ab ig CREB et n M ali of ng CRY1 ol FoxO Gluconeogenesis ntr Co nal ptio scri Tran Direct Stimulatory Multistep Inhibitory Separation of Subunits Transcriptional Receptor GTPase Modification Modification or Cleavage Products Inhibitory Modification Enzyme G-protein Direct Inhibitory Tentative Stimulatory Joining of Subunits Kinase pro-apoptotic Acetylase Modification Modification Translocation Phosphatase pro-survival Deacetylase Multistep Stimulatory Tentative Inhibitory Transcriptional Transcription Factor Modification Modification GAP/GEF Stimulatory Modification Ribosomal subunit Caspase Printed in the USA on recycled paper (25% post-consumer waste fiber) using vegetable inks and processed chlorine free. © 2015 Cell Signaling Technology, Inc. Cell Signaling Technology® and CST™ are trademarks of Cell Signaling Technology, Inc. Please see our website for all pathway diagram backgrounds. www.cellsignal.com/cellularpws 14PSTREFMCELM0259ENG_00.
Recommended publications
  • HDAC7 Sikens the Heart

    HDAC7 Sikens the Heart

    The black sheep of class IIa: HDAC7 SIKens the heart Joshua G. Travers, … , Tianjing Hu, Timothy A. McKinsey J Clin Invest. 2020;130(6):2811-2813. https://doi.org/10.1172/JCI137074. Commentary Class IIa histone deacetylases (HDACs) repress cardiomyocyte hypertrophy through association with the prohypertrophic transcription factor (TF) myocyte enhancer factor-2 (MEF2). The four class IIa HDACs — HDAC4, -5, -7, and -9 — are subject to signal-dependent phosphorylation by members of the Ca2+/calmodulin-dependent protein kinase (CaMK) group. In response to stress, HDAC4, HDAC5, and HDAC9 undergo phosphorylation-induced nuclear export in cardiomyocytes, freeing MEF2 to stimulate progrowth genes; it was generally assumed that HDAC7 is also antihypertrophic. However, in this issue of the JCI, Hsu and colleagues demonstrate that, in sharp contrast to the other class IIa HDACs, HDAC7 is constitutively localized to the cardiomyocyte cytoplasm, where it promotes cardiac hypertrophy. Phosphorylation of HDAC7 by the CaMK group member salt-inducible kinase 1 (SIK1) stabilized the deacetylase, leading to increased expression of c-Myc, which in turn stimulated a pathological gene program. These unexpected findings highlight the SIK1/HDAC7 signaling axis as a promising target for the treatment of cardiac hypertrophy and heart failure. Find the latest version: https://jci.me/137074/pdf The Journal of Clinical Investigation COMMENTARY The black sheep of class IIa: HDAC7 SIKens the heart Joshua G. Travers, Tianjing Hu, and Timothy A. McKinsey Division of Cardiology, Department of Medicine, and Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. repress gene expression, block cardiac hypertrophy by associating with the myo- Class IIa histone deacetylases (HDACs) repress cardiomyocyte hypertrophy cyte enhancer factor-2 (MEF2) transcrip- through association with the prohypertrophic transcription factor (TF) tion factor (TF) (11).
  • An Overview of the Role of Hdacs in Cancer Immunotherapy

    An Overview of the Role of Hdacs in Cancer Immunotherapy

    International Journal of Molecular Sciences Review Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy Debarati Banik, Sara Moufarrij and Alejandro Villagra * Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, 800 22nd St NW, Suite 8880, Washington, DC 20052, USA; [email protected] (D.B.); [email protected] (S.M.) * Correspondence: [email protected]; Tel.: +(202)-994-9547 Received: 22 March 2019; Accepted: 28 April 2019; Published: 7 May 2019 Abstract: Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration.
  • Supporting Online Material

    Supporting Online Material

    1 2 3 4 5 6 7 Supplementary Information for 8 9 Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic 10 retinopathy 11 12 *Samuel A. Mills, *Andrew I. Jobling, *Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey, Joanna A. Phipps, 13 Ursula Greferath, Gene Venables, Vickie H.Y. Wong, Connie H.Y. Wong, Zheng He, Flora Hui, James C. 14 Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher 15 * Joint first authors 16 17 Corresponding author: 18 Prof. Erica L. Fletcher. Department of Anatomy & Neuroscience. The University of Melbourne, Grattan St, 19 Parkville 3010, Victoria, Australia. 20 Email: [email protected] ; Tel: +61-3-8344-3218; Fax: +61-3-9347-5219 21 22 This PDF file includes: 23 24 Supplementary text 25 Figures S1 to S10 26 Tables S1 to S7 27 Legends for Movies S1 to S2 28 SI References 29 30 Other supplementary materials for this manuscript include the following: 31 32 Movies S1 to S2 33 34 35 36 1 1 Supplementary Information Text 2 Materials and Methods 3 Microglial process movement on retinal vessels 4 Dark agouti rats were anaesthetized, injected intraperitoneally with rhodamine B (Sigma-Aldrich) to label blood 5 vessels and retinal explants established as described in the main text. Retinal microglia were labelled with Iba-1 6 and imaging performed on an inverted confocal microscope (Leica SP5). Baseline images were taken for 10 7 minutes, followed by the addition of PBS (10 minutes) and then either fractalkine or fractalkine + candesartan 8 (10 minutes) using concentrations outlined in the main text.
  • Extracellular Adenosine Triphosphate and Adenosine in Cancer

    Extracellular Adenosine Triphosphate and Adenosine in Cancer

    Oncogene (2010) 29, 5346–5358 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW Extracellular adenosine triphosphate and adenosine in cancer J Stagg and MJ Smyth Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Adenosine triphosphate (ATP) is actively released in the mulated the hypothesis of purinergic neurotransmission extracellular environment in response to tissue damage (Burnstock, 1972). Burnstock’s hypothesis that ATP and cellular stress. Through the activation of P2X and could be released by cells to perform intercellular P2Y receptors, extracellular ATP enhances tissue repair, signaling was initially met with skepticism, as it seemed promotes the recruitment of immune phagocytes and unlikely that a molecule that acts as an intracellular dendritic cells, and acts as a co-activator of NLR family, source of energy would also function as an extracellular pyrin domain-containing 3 (NLRP3) inflammasomes. messenger. Nevertheless, Burnstock pursued his work The conversion of extracellular ATP to adenosine, in and, together with Che Su and John Bevan, reported contrast, essentially through the enzymatic activity of the that ATP was also released from sympathetic nerves ecto-nucleotidases CD39 and CD73, acts as a negative- during stimulation (Su et al., 1971). Three decades later, feedback mechanism to prevent excessive immune responses. following the cloning and characterization of ATP and Here we review the effects of extracellular ATP and adenosine adenosine cell surface receptors, purinergic signaling is a on tumorigenesis. First, we summarize the functions of well-established concept and constitutes an expanding extracellular ATP and adenosine in the context of tumor field of research in health and disease, including cancer immunity.
  • Determining HDAC8 Substrate Specificity by Noah Ariel Wolfson A

    Determining HDAC8 Substrate Specificity by Noah Ariel Wolfson A

    Determining HDAC8 substrate specificity by Noah Ariel Wolfson A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Biological Chemistry) in the University of Michigan 2014 Doctoral Committee: Professor Carol A. Fierke, Chair Professor Robert S. Fuller Professor Anna K. Mapp Associate Professor Patrick J. O’Brien Associate Professor Raymond C. Trievel Dedication My thesis is dedicated to all my family, mentors, and friends who made getting to this point possible. ii Table of Contents Dedication ....................................................................................................................................... ii List of Figures .............................................................................................................................. viii List of Tables .................................................................................................................................. x List of Appendices ......................................................................................................................... xi Abstract ......................................................................................................................................... xii Chapter 1 HDAC8 substrates: Histones and beyond ...................................................................... 1 Overview ..................................................................................................................................... 1 HDAC introduction
  • Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives

    Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives

    cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids.
  • Molecular Interactions Underpinning the Phenotype of Hibernation in Mammals Matthew T

    Molecular Interactions Underpinning the Phenotype of Hibernation in Mammals Matthew T

    © 2019. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2019) 222, jeb160606. doi:10.1242/jeb.160606 REVIEW Molecular interactions underpinning the phenotype of hibernation in mammals Matthew T. Andrews* ABSTRACT most mammals. This Review covers recent advances in the Mammals maintain a constant warm body temperature, facilitating a molecular biology of hibernation, with a focus on molecular wide variety of metabolic reactions. Mammals that hibernate have the interactions underpinning the hibernation phenotype. Specific – ability to slow their metabolism, which in turn reduces their body topics include the torpor arousal cycle, the role of small temperature and leads to a state of hypothermic torpor. For this molecules, changes in gene expression, cold-inducible RNA- metabolic rate reduction to occur on a whole-body scale, molecular binding proteins, the somatosensory system and emerging interactions that change the physiology of cells, tissues and organs information on hibernating primates. This new information not are required, resulting in a major departure from normal mammalian only is beginning to explain how natural hibernators survive homeostasis. The aim of this Review is to cover recent advances in the physiological extremes that would be lethal to most mammals, but molecular biology of mammalian hibernation, including the role of also identifies molecular mechanisms that may prove useful to small molecules, seasonal changes in gene expression, cold- human medicine. inducible RNA-binding proteins,
  • Biotin Rescues Mitochondrial Dysfunction and Neurotoxicity in a Tauopathy Model

    Biotin Rescues Mitochondrial Dysfunction and Neurotoxicity in a Tauopathy Model

    Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model Kelly M. Lohra,b, Bess Frostc, Clemens Scherzerd, and Mel B. Feanya,1 aDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; bDepartment of Biology, Washington & Jefferson College, Washington, PA 15301; cDepartment of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229; and dNeurogenomics Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 17, 2020 (received for review December 21, 2019) Mitochondrial and metabolic dysfunction are often implicated in We combined Drosophila genetics with a variety of molecular neurological disease, but effective mechanism-based therapies re- and cellular approaches to explore the role of mitochondrial and main elusive. We performed a genome-scale forward genetic metabolic pathways in tauopathy and neuronal survival. We screen in a Drosophila model of tauopathy, a class of neurodegen- identified dysfunction within the biotin pathway in tauopathy and erative disorders characterized by the accumulation of the protein showed that biotin supplementation both rescues mitochondrial tau, and identified manipulation of the B-vitamin biotin as a po- deficits and improves neuronal health in vivo. Furthermore, we tential therapeutic approach in tauopathy. We show that tau demonstrate parallel mechanisms in human Alzheimer’s disease transgenic flies have an innate biotin deficiency due to tau-medi- brain. Together, these findings emphasize the importance of ated relaxation of chromatin and consequent aberrant expression biotin handling in mitochondrial and metabolic processes in of multiple biotin-related genes, disrupting both carboxylase and neurons, suggesting a key role for biotin in both the healthy and mitochondrial function.
  • HDAC7, Active Recombinant Human Protein Expressed in Sf9 Cells

    HDAC7, Active Recombinant Human Protein Expressed in Sf9 Cells

    Catalog # Aliquot Size H89-31G-05 5 µg H89-31G-10 10 µg HDAC7, Active Recombinant human protein expressed in Sf9 cells Catalog # H89-31G Lot # B1893-8 Product Description Specific Activity Recombinant human HDAC7 (501-end) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. 520,000 The gene accession number is NM_015401. 390,000 Gene Aliases 260,000 HD7A; HDAC7A; DKFZp586J0917; FLJ99588 130,000 Activity (RLU) Formulation 0 0 100 200 300 400 Recombinant protein stored in 50mM Tris-HCl, pH 7.5, Protein (ng) 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM The specific activity of HDAC7 was determined to be 80 DTT, 0.1mM PMSF, 25% glycerol. RLU/min/ng as per activity assay protocol. Storage and Stability Purity Store product at –70oC. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles. The purity of HDAC7 was determined to be >95% by densitometry. Scientific Background Approx. MW 80kDa. HDAC7 or Histone deacetylase 7 belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. The protein encoded by HDAC7 gene has sequence homology to members of the histone deacetylase family whose protein promotes repression mediated via the transcriptional co-repressor HDAC7, Active SMRT (1). HDAC7 interacts with b-catenin keeping Recombinant human protein expressed in Sf9 cells endothelial cells in a low proliferation stage. HDAC7 regulates NUR77 and apoptosis in developing thymocytes Catalog # H89-31G (2).
  • Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives

    Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives

    Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation de Andrade Mello, Paola, Robson Coutinho-Silva, and Luiz Eduardo Baggio Savio. 2017. “Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives.” Frontiers in Immunology 8 (1): 1526. doi:10.3389/fimmu.2017.01526. http://dx.doi.org/10.3389/ fimmu.2017.01526. Published Version doi:10.3389/fimmu.2017.01526 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493041 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA REVIEW published: 14 November 2017 doi: 10.3389/fimmu.2017.01526 Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives Paola de Andrade Mello1, Robson Coutinho-Silva 2* and Luiz Eduardo Baggio Savio2* 1 Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Cancer is still one of the world’s most pressing health-care challenges, leading to a high number of deaths worldwide. Immunotherapy is a new developing therapy that Edited by: boosts patient’s immune system to fight cancer by modifying tumor–immune cells Salem Chouaib, interaction in the tumor microenvironment (TME).
  • Design and Synthesis of Novel Classes of Hdacs and Kmts Inhibitors

    Design and Synthesis of Novel Classes of Hdacs and Kmts Inhibitors

    University of East Anglia School of Pharmacy Design and synthesis of novel classes of HDACs and KMTs inhibitors by Remy Thomas Narozny Supervisor: Prof. A. Ganesan Second Supervisor: Prof. Mark Searcey Thesis for the degree of Doctor of Philosophy November 2018 This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that use of any information derived therefrom must be in accordance with current UK Copyright Law. In addition, any quotation or extract must include full attribution. “Your genetics is not your destiny.” George McDonald Church Abstract For long, scientists thought that our body was driven only by our genetic code that we inherited at birth. However, this determinism was shattered entirely and proven as false in the second half of the 21st century with the discovery of epigenetics. Instead, cells turn genes on and off using reversible chemical marks. With the tremendous progression of epigenetic science, it is now believed that we have a certain power over the expression of our genetic traits. Over the years, these epigenetic modifications were found to be at the core of how diseases alter healthy cells, and environmental factors and lifestyle were identified as top influencers. Epigenetic dysregulation has been observed in every major domain of medicine, with a reported implication in cancer development, neurodegenerative pathologies, diabetes, infectious disease and even obesity. Substantially, an epigenetic component is expected to be involved in every human disease. Hence, the modulation of these epigenetics mechanisms has emerged as a therapeutic strategy.
  • Cell Signaling and Regulation of Metabolism Objectives

    Cell Signaling and Regulation of Metabolism Objectives

    Cell Signaling and Regulation of Metabolism Objectives By the end of this lecture, students are expected to: • Differentiate different steps in signaling pathways • Describe the second messenger systems • Recognize the function of signaling pathways for • Signal transmission • Amplification • Discuss the role of signaling pathways in regulation and integration of metabolism No cell lives in isolation • Cells communicate with each other • Cells send and receive information (signals) • Information is relayed within cell to produce a response Signaling Process • Recognition of signal – Receptors • Transduction – Change of external signal into intracellular message with amplification and formation of second messenger • Effect – Modification of cell metabolism and function General Signaling Pathway Signaling Cascades Recognition • Performed by receptors • Ligand will produce response only in cells that have receptors for this particular ligand • Each cell has a specific set of receptors Different Responses to the Same Signaling Molecule. (A) Different Cells Different Responses to the Same Signaling Molecule. (B) One Cell but, Different Pathways Hypoglycemia Glucagon secretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzyme phosphorylation P P Glycogen synthase Glycogen phosphorylase (Inactive form) (Active form) Inhibition of glycogenesis Stimulation of glycogenolysis GTP-Dependant Regulatory Proteins (G-Proteins) G-Proteins: Trimeric membrane proteins (αβγ) G-stimulatory (Gs) and G-inhibitory (Gi) binds to GTP/GDP