Ch 08 - Glycogen & Pentose Phosphate PDF

Chapter 8 Carbohydrates II: Glycogen Metabolism, the Pentose Phosphate Pathway, Glycoconjugates, and Extracellular Matrices Biochemistry First Edition John Tansey Lecture PowerPoints Tanea Reed Chapter 8 Outline 8.1 8.2 8.3 8.4 Glycogen metabolism The pentose phosphate pathway Carbohydrates in glyco...

Chapter 8 Carbohydrates II: Glycogen Metabolism, the Pentose Phosphate Pathway, Glycoconjugates, and Extracellular Matrices Biochemistry First Edition John Tansey Lecture PowerPoints Tanea Reed Chapter 8 Outline 8.1 8.2 8.3 8.4 Glycogen metabolism The pentose phosphate pathway Carbohydrates in glycoconjugates Extracellular matrices and biofilms Copyright © 2019 John Wiley & Sons, Inc. 2 Learning Objectives § Analyze the pathways of glycogen biosynthesis and breakdown, and the regulation of these pathways. § Describe the reactions of the pentose phosphate pathway. Copyright © 2019 John Wiley & Sons, Inc. 3 Section 8.1 Learning Objective § Analyze the pathways of glycogen biosynthesis and breakdown, and the regulation of these pathways. Copyright © 2019 John Wiley & Sons, Inc. 4 Glycogen § A stored form of glucose Why not just store glucose monomers? At least two reasons… § Highly branched polymer of α-1,4 and α-1,6 linked glucose monomers, with a single molecule of the protein glycogenin at the core § Glygogen is synthesized and degraded in situ § Storage is regulated by epinephrine and norepinephrine Copyright © 2019 John Wiley & Sons, Inc. 5 Structure of Glycogen Figure 8.2 Glycogen is a storage form of glucose. Copyright © 2019 John Wiley & Sons, Inc. 6 Glycogenesis Defined § Glycogenesis is the synthesis of glycogen. § Requires several important components Glycogenin (core protein—also an enzyme!) Glycogen synthase Branching enzyme Starts with UDP-glucose – a sugar-nucleotide o UTP “activates” glucose for further metabolism UTP + glucose à UDP-glucose + Pi Copyright © 2019 John Wiley & Sons, Inc. 7 Synthesis of Glycogen Figure 8.3 Synthesis of glycogen. Copyright © 2019 John Wiley & Sons, Inc. 8 Branching Enzyme Figure 8.4 Branching enzyme. Copyright © 2019 John Wiley & Sons, Inc. 9 Glycogenolysis Defined § Glycogenolysis is the breakdown of glycogen. § Is degraded one glucose at a time Until we get too close to a branch! § Requires several important components Glycogen phosphorylase + Pi Glycogen debranching enzyme Copyright © 2019 John Wiley & Sons, Inc. 10 Glycogen Breakdown Figure 8.5 Glycogen breakdown. Copyright © 2019 John Wiley & Sons, Inc. 11 Regulation of Glycogenesis and Glycogenolysis § Glycogen phosphorylase and glycogen synthase must be regulated. Example of reciprocal regulation of processes § PKA is the main regulator of both enzymes. Figure 8.7 Overview of the regulation of glycogen metabolism. Copyright © 2019 John Wiley & Sons, Inc. 12 Allosteric Regulation of Glycogen Metabolism § ATP and glucose-6-phosphate are allosteric regulators § Glycogen synthase and glycogen phosphorylase naming convention: A—active B—less active § Phosphorylation determines whether the enzyme is active or not § Glycogen synthase and glycogen phosphorylase work in opposition (reciprocal regulation!) Copyright © 2019 John Wiley & Sons, Inc. 13 Regulation of Glycogen Synthesis § Pathways that phosphorylate glycogen synthase will inactivate it § Glycogen synthase: phosphorylated by GSK-3 and PKA § Regulated by PKB (Akt), PP1, and G-6-P Figure 8.10 Regulation of glycogen synthesis. Copyright © 2019 John Wiley & Sons, Inc. 14 Regulation of Glycogen Breakdown § Glycogen phosphorylase is activated by phosphorylation and deactivated by dephosphorylation. § Glycogen phosphorylase activated by PKA and Ca2+ § Dephosphorylated by PP1 Figure 8.11 Regulation of glycogen phosphorylase. Copyright © 2019 John Wiley & Sons, Inc. 15 G Protein-Coupled Receptors (GPCR) Cell Signaling Cascade § Ligand bind to receptor (GPCR). [slow] Glucagon = “low blood sugar—let’s raise it” [fast] Epinephrine = “Eek! A mouse—run for it!” § Adenylate cyclase is activated. cAMP is generated from ATP. § Glycogen metabolism is dependent on PKA (PKA is cAMP dependent). § Termination of signal Copyright © 2019 John Wiley & Sons, Inc. 16 GPCR Cell Signaling Cascade— Glucagon and Epinephrine Figure 8.8 Action of glucagon and epinepherine on the cell. Copyright © 2019 John Wiley & Sons, Inc. 17 Insulin Signaling Cascade § Ligand (insulin) binds to receptor (insulin receptor). [slow] Insulin = “high blood sugar—let’s lower it” § Receptor is dimerized. § Autophosphorylation occurs. § Akt (PKB) is activated. § Stimulates glycogenesis § Blocks glycogenolysis by stimulating PP1 Copyright © 2019 John Wiley & Sons, Inc. 18 Insulin Signaling Figure 8.9 Insulin signaling. Copyright © 2019 John Wiley & Sons, Inc. 19 Effects of Hormones on Glucose Metabolism Glycogenesis Glycogenolysis Insulin in muscle Insulin in liver Glucagon in muscle Glucagon in liver Epinephrine in muscle Epinephrine in liver Up Up – Down Down Down Down Down – Up Up Up Copyright © 2019 John Wiley & Sons, Inc. 20 Metabolism 21 Section 8.2 Learning Objective § Describe (not memorize!) the reactions of the pentose phosphate pathway. Copyright © 2019 John Wiley & Sons, Inc. 22 Pentose Phosphate Pathway § Runs alongside glycolysis/gluconeogenesis (hexose phosphate pathway) § Produces monosaccharides, NADPH, and antioxidants NADPH gives reducing power (e-) for biosynthesis § Also known as the pentose phosphate shunt, hexose monophosphate shunt, and phosphogluconate pathway § Is divided into two phases Oxidative – generates pentoses & produces NADPH Nonoxidative – regenerates glycolysis intermediates Copyright © 2019 John Wiley & Sons, Inc. 23 Pentose Phosphate Pathway Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Relationship Between Glycolysis & Pentose Phosphate Pathway Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Pentose Phosphate Pathway Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Regulation of the Pentose Phosphate Pathway § First step (glucose-6-phosphate dehydrogenase) is regulated by levels of NADP+. § Monosaccharides (e.g. ribose) can be converted by PPP to hexoses for entry into glycolysis. § Carbohydrates can be oxidized into CO2. Copyright © 2019 John Wiley & Sons, Inc. 27 Glutathione and the Pentose Phosphate Pathway 28 Copyright Copyright © 2019 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in Section 117 of the 1976 United States Act without the express written permission of the copyright owner is unlawful. Request for further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publisher assumes no responsibility for errors, omissions, or damages, caused by the use of these programs or from the use of the information contained herein. Copyright © 2019 John Wiley & Sons, Inc. 29