Glycogen Metabolism in Humans☆,☆☆
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Phosphorylation of Mcardle Phosphorylase Induces Activity (Human Skeletal Muscle/Protein Kinase) CESARE G
Proc. Nati. Acad. Sci. USA Vol. 78, No. 5, pp. 2688-2692, May 1981 Biochemistry Phosphorylation of McArdle phosphorylase induces activity (human skeletal muscle/protein kinase) CESARE G. CERRI AND JOSEPH H. WILLNER Department of Neurology and H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University College of Physicians and Surgeons, New York, New York 10032 Communicated by Harry Grundfest, January 7, 1981 ABSTRACT In McArdle disease, myophosphorylase defi- mediate between those of phosphorylases b and a. Karpatkin ciency, enzyme activity is absent but the presence of an altered et al. (19, 20) found that incubation of human platelets with enzyme protein can frequently be demonstrated. We have found MgATP+ resulted in an increase in total phosphorylase activity that phosphorylation of this protein in vitro can result in catalytic and concluded that the data were "consistent with the presence activity. We studied muscle of four patients; all lacked myophos- in human platelets of inactive dimer and monomer species of phorylase activity, but myophosphorylase protein was demon- phosphorylase, which require MgATP for activation." Because strated by immunodiffusion or gel electrophoresis. Incubation of activation of these isozymes was probably due to protein phos- muscle homogenate supernatants with cyclic AMP-dependent pro- phorylation and also because incomplete phosphorylation could tein kinase and ATP resulted in phosphorylase activity. The ac- tivated enzyme comigrated with normal human myophosphory- result in reduced activity, we evaluated the possibility that the lase in gel electrophoresis. Incubation with [y-32P]ATP resulted activity ofphosphorylase in McArdle muscle could be restored in incorporation of 32P into the band possessing phosphorylase by phosphorylation of the inactive phosphorylase protein pres- activity. -
Articles Catalytic Cycling in Β-Phosphoglucomutase: a Kinetic
9404 Biochemistry 2005, 44, 9404-9416 Articles Catalytic Cycling in â-Phosphoglucomutase: A Kinetic and Structural Analysis†,‡ Guofeng Zhang, Jianying Dai, Liangbing Wang, and Debra Dunaway-Mariano* Department of Chemistry, UniVersity of New Mexico, Albuquerque, New Mexico 87131-0001 Lee W. Tremblay and Karen N. Allen* Department of Physiology and Biophysics, Boston UniVersity School of Medicine, Boston, Massachusetts 02118-2394 ReceiVed March 26, 2005; ReVised Manuscript ReceiVed May 18, 2005 ABSTRACT: Lactococcus lactis â-phosphoglucomutase (â-PGM) catalyzes the interconversion of â-D-glucose 1-phosphate (â-G1P) and â-D-glucose 6-phosphate (G6P), forming â-D-glucose 1,6-(bis)phosphate (â- G16P) as an intermediate. â-PGM conserves the core domain catalytic scaffold of the phosphatase branch of the HAD (haloalkanoic acid dehalogenase) enzyme superfamily, yet it has evolved to function as a mutase rather than as a phosphatase. This work was carried out to identify the structural basis underlying this diversification of function. In this paper, we examine â-PGM activation by the Mg2+ cofactor, â-PGM activation by Asp8 phosphorylation, and the role of cap domain closure in substrate discrimination. First, the 1.90 Å resolution X-ray crystal structure of the Mg2+-â-PGM complex is examined in the context of + + previously reported structures of the Mg2 -R-D-galactose-1-phosphate-â-PGM, Mg2 -phospho-â-PGM, and Mg2+-â-glucose-6-phosphate-1-phosphorane-â-PGM complexes to identify conformational changes that occur during catalytic turnover. The essential role of Asp8 in nucleophilic catalysis was confirmed by demonstrating that the D8A and D8E mutants are devoid of catalytic activity. -
HEMOLYTIC ANEMIA in DISORDERS of REO CELL METABOLISM TOPICS in HEMATOLOGY Series Editor: Maxwell M
HEMOLYTIC ANEMIA IN DISORDERS OF REO CELL METABOLISM TOPICS IN HEMATOLOGY Series Editor: Maxwell M. Wintrobe, M.D. University of Utah, Salt Lake City THE RESPIRATORY FUNCTIONS OF BLOOD Lars Garby, M.D. and Jerry Meldon, M.D. HEMOLYTIC ANEMIA IN DISORDERS OF RED CELL METABOLISM Ernest Beutler, MD. TRACE ELEMENTS AND IRON IN HUMAN METABOLISM Ananda S. Prasad, M.D. HEMOLYTIC ANEMIA IN DISORDERS OF REO CELL METABOLISM Ernest Beutler, M. O. City of Hope National Medical Center Duarte, California PLENUM MEDICAL BOOK COMPANY· New York and London Library of Congress Cataloging in Publication Data Beutler, Ernest. Hemolytic anemia in disorders of red cell metabolism. (Topics in hematology) Includes index. 1. Hemolytic anemia. 2. Erythrocyte disorders. I. Title. II. Series. CR641.7.H4B48 616.1'52 78-2391 ISBN 978-1-4684-2459-1 ISBN 978-1-4684-2457-7 (eBook) DOI 10.1007/978-1-4684-2457-7 © 1978 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition 1978 227 West 17th Street, New York, N.Y. 10011 Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher FOREWORD I am prepared to predict that this monograph by Dr. Ernest Beutler will long serve as a model for monographs dealing with topics in medical science. I make this bold statement because we encounter in this work a degree of accuracy and authoritativeness well beyond that found in much of the medical literature. -
Liver Glucose Metabolism in Humans
Biosci. Rep. (2016) / 36 / art:e00416 / doi 10.1042/BSR20160385 Liver glucose metabolism in humans Mar´ıa M. Adeva-Andany*1, Noemi Perez-Felpete*,´ Carlos Fernandez-Fern´ andez*,´ Cristobal´ Donapetry-Garc´ıa* and Cristina Pazos-Garc´ıa* *Nephrology Division, Hospital General Juan Cardona, c/ Pardo Bazan´ s/n, 15406 Ferrol, Spain Synopsis Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and con- nected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic path- ways. During the post-prandial period, most glucose 6-phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate and UDP–glucose. Minor amounts of UDP–glucose are used to form UDP–glucuronate and UDP– galactose, which are donors of monosaccharide units used in glycosylation. A second pathway of glucose 6-phosphate metabolism is the formation of fructose 6-phosphate, which may either start the hexosamine pathway to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA) cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids, when excess glucose is present within the hepatocyte. Finally, glucose 6-phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate pathway. -
BMC Genetics Biomed Central
BMC Genetics BioMed Central Research article Open Access Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPP1R3A locus Alex SF Doney3, Bettina Fischer1, Joanne E Cecil4, Patricia TW Cohen5, Douglas I Boyle2, Graham Leese2, Andrew D Morris2 and Colin NA Palmer*1 Address: 1Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. Scotland, United Kingdom, 2Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. Scotland, United Kingdom, 3Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom, 4Department of Psychology, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom and 5Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom Email: Alex SF Doney - [email protected]; Bettina Fischer - [email protected]; Joanne E Cecil - [email protected]; Patricia TW Cohen - [email protected]; Douglas I Boyle - [email protected]; Graham Leese - [email protected]; Andrew D Morris - [email protected]; Colin NA Palmer* - [email protected] * Corresponding author Published: 28 June 2003 Received: 07 January 2003 Accepted: 28 June 2003 BMC Genetics 2003, 4:11 This article is available from: http://www.biomedcentral.com/1471-2156/4/11 © 2003 Doney et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. -
MODY 2 Presenting As Neonatal Hyperglycaemia: a Need to Reshape the Definition of ªneonatal Diabetesº?
Letters 1331 MODY 2 presenting as neonatal sidered a stringent criterium for selecting patients. We ob- served that the moderate low birth weight of patients No. 1 hyperglycaemia: a need to reshape and No. 3 was probablyinfluenced bya mutation of paternal the definition of ªneonatal diabetesº? origin and subsequent low fetal insulin secretion. Mutations in the GK represent the more frequent cause of Dear Sir, MODY in some series [3] and it has been calculated that up Neonatal diabetes mellitus is defined as a rare condition to 6% of familial Type II non-insulin-dependent) diabetes 1:400.000 live births) of unknown origin, characterised byhy- mellitus could bear a MODY 2 allele [3]. We and others have perglycaemia occurring in the first month of life that requires ex- frequentlyobserved that the mutation-carryingparent of chil- ogenous insulin therapy[1, 2]. The derangement of glucose me- dren with MODY 2 is unaware of his or her hyperglycaemia. tabolism in newborns affected bythis condition could be perma- As a consequence, some previouslydescribed cases of perma- nent permanent neonatal diabetes mellitus, PNDM) or could nent neonatal diabetes of unknown origin might be linked to orcouldnot)recurafterremissionofhyperglycaemiatransient GK mutations in both alleles, even in the absence of consan- neonataldiabetesmellitus,TNDM)[1,2]. Inapedigreewith ma- guineityloop i.e. compound heterozygous). Neonatal, insu- turityonset diabetes of the youngMODY) harbouring the glu- lin-requiring, permanent diabetes mellitus is the main feature cokinase GK, MODY 2) mutation Q38P, we followed a new of GK knock-out mice models [5]. pregnancyofthenon-mutantmotheroftheindexcase.Wefound We believe that the definition of neonatal diabetes currently that 15 days after delivery her child presented hyperglycaemia inuse[1,2]needstoberevisedinorderto:firstly,permanently in- 11.7 mmol) with dehydration and mild ketosis Table 1, patient corporate the concept that TNDM in some cases linked to pa- No. -
Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’
Journal of Neuromuscular Diseases 8 (2021) 401–417 401 DOI 10.3233/JND-200621 IOS Press Systematic Review Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’ A. Mantaa,b, S. Spendiffb, H. Lochmuller¨ b,c,d,e,f and R. Thompsonb,∗ aFaculty of Medicine, University of Ottawa, Ottawa, ON, Canada bChildren’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada cDepartment of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany dCentro Nacional de An´alisis Gen´omico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain eDivision of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Canada f Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada Abstract. Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intoler- ance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and -oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforemen- tioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. -
Glycogenesis
Glycogenesis Glycogen is the storage form of glucose in animals and humans which is analogous to the starch in plants. Glycogen is synthesized and stored mainly in the liver and the muscles. Structurally, glycogen is very similar to amylopectin with alpha acetal linkages, however, it has even more branching and more glucose units are present than in amylopectin. Various samples of glycogen have been measured at 1,700-600,000 units of glucose. The structure of glycogen consists of long polymer chains of glucose units connected by an alpha acetal linkage. All of the monomer units are alpha-D-glucose, and all the alpha acetal links connect C # 1 of one glucose to C # 4 of the next glucose. The branches are formed by linking C # 1 to a C # 6 through acetal linkages. In glycogen, the branches occur at intervals of 8-10 glucose units (in amylopectin the branches are separated by 12-20 glucose units). Carbon # 1 is called the anomeric carbon and is the center of an acetal functional group. The Alpha position is defined as the ether oxygen being on the opposite side of the ring as the C # 6. In the chair structure this results in a downward projection. Plants make starch and cellulose through the photosynthesis processes. Animals and human in turn eat plant materials and products. Digestion is a process of hydrolysis where the starch is broken ultimately into the various monosaccharides. A major product is of course glucose which can be used immediately for metabolism to make energy. The glucose that is not used immediately is converted in the liver and muscles into glycogen for storage by the process of glycogenesis. -
Guaiacol As a Drug Candidate for Treating Adult Polyglucosan Body Disease
Guaiacol as a drug candidate for treating adult polyglucosan body disease Or Kakhlon, … , Wyatt W. Yue, H. Orhan Akman JCI Insight. 2018;3(17):e99694. https://doi.org/10.1172/jci.insight.99694. Research Article Metabolism Therapeutics Graphical abstract Find the latest version: https://jci.me/99694/pdf RESEARCH ARTICLE Guaiacol as a drug candidate for treating adult polyglucosan body disease Or Kakhlon,1 Igor Ferreira,2 Leonardo J. Solmesky,3 Netaly Khazanov,4 Alexander Lossos,1 Rafael Alvarez,5 Deniz Yetil,6 Sergey Pampou,7 Miguel Weil,3,8 Hanoch Senderowitz,4 Pablo Escriba,5 Wyatt W. Yue,2 and H. Orhan Akman9 1Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 2Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.3 Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. 4Department of Chemistry, Bar Ilan University, Ramat Gan, Israel. 5Laboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain. 6Connecticut College, Newington, Connecticut USA. 7Columbia University Department of Systems Biology Irving Cancer Research Center, New York, New York, USA. 8Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The George S. Wise Faculty for Life Sciences, Sagol School of Neurosciences, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel. 9Columbia University Medical Center Department of Neurology, Houston Merritt Neuromuscular diseases research center, New York, New York, USA. Adult polyglucosan body disease (APBD) is a late-onset disease caused by intracellular accumulation of polyglucosan bodies, formed due to glycogen-branching enzyme (GBE) deficiency. -
Datasheet: VPA00226
Datasheet: VPA00226 Description: RABBIT ANTI ALDOA Specificity: ALDOA Format: Purified Product Type: PrecisionAb™ Polyclonal Isotype: Polyclonal IgG Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse, Rat Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Rabbit Ig fraction prepared by ammonium sulphate precipitation Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers Immunogen KLH conjugated synthetic peptide between 66-95 amino acids from the N-terminal region of human ALDOA External Database UniProt: Links P04075 Related reagents Entrez Gene: 226 ALDOA Related reagents Page 1 of 2 Synonyms ALDA Specificity Rabbit anti Human ALDOA antibody recognizes fructose-bisphosphate aldolase A, also known as epididymis secretory sperm binding protein Li 87p, fructose-1,6-bisphosphate triosephosphate-lyase, lung cancer antigen NY-LU-1 and muscle-type aldolase. Encoded by the ALDOA gene, fructose-bisphosphate aldolase A is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. -
Maternal Or Paternal Diabetes and Its Crucial Role in Offspring Birth
H OH metabolites OH Editorial Maternal or Paternal Diabetes and Its Crucial Role in Offspring Birth Weight and MODY Diagnosis Valeria Calcaterra 1,2,* , Angela Zanfardino 3 , Gian Vincenzo Zuccotti 2,4 and Dario Iafusco 3 1 Pediatric and Adolescence Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy 2 Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milano, Italy; [email protected] 3 Department of Pediatrics, Regional Center of Pediatric Diabetology “G. Stoppoloni”, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy; [email protected] (A.Z.); [email protected] (D.I.) 4 Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milano, Italy * Correspondence: [email protected] Received: 17 September 2020; Accepted: 26 September 2020; Published: 28 September 2020 Abstract: Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic autosomal dominant diseases, which accounts for 1–2% of all diabetes cases. Pregnancy represents a crucial time to diagnose MODY forms due to the 50% risk of inheritance in offspring of affected subjects and the potential implications on adequate fetal weight. Not only a history of maternal diabetes may affect the birth weight of offspring, paternal diabetes should also be taken into consideration for a correct pathogenetic diagnosis. The crucial role of maternal and paternal diabetes inheritance patterns and the impact of this inherited mutation on birthweight and the MODY diagnosis was discussed. Keywords: mother; father; diabetes; birthweight; MODY Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic autosomal dominant diseases, which accounts for 1–2% of all diabetes cases [1]. -
Maladies Convention Mal
maladies métaboliques monogéniques héréditaires rares 1 avenant à la convention avec les centres de référence – annexe OMIM # FULL NAME A. disorders of amino acid metabolism 1 261600 classical phenylketonuria and hyperphenylala- ninemia 2 261640 phenylketonuria due to PTPS deficiency 3 261630 phenylketonuria due to DHPR deficiency 4 264070 phenylketonuria due to PCD deficiency 5 128230 DOPA-responsive dystonia (TH, SPR, GCH1) 6 248600 leucinose, maple syrup urine disease (MSUD) 7 276700 tyrosinemia type 1 8 276600 tyrosinemia type 2 9 276710 tyrosinemia type 3 10 203500 alkaptonuria 11 236200 homocystinuria, B6 responsive and non responsive 12 236250 homocystinuria due to MTHFR deficiency 13 236270-250940 homocystinuria-megaloblastic anemia Cbl E & G type 14 250850 methionine S-adenosyltransferase deficiency 15 606664 glycine N-methyltransferase deficiency 16 180960 S-adenosylhomocystine hydrolase deficiency 17 237300 hyperammonemia due to CPS deficiency 18 311250 hyperammonemia due to OTC deficiency 19 215700 citrullinemia type I 20 605814-603471 citrullinemia type II 21 207900 argininosuccinic aciduria (ASL deficiency) 22 207800 argininemia (arginase deficiency) 23 237310 hyperammonemia due to NAGS deficiency 24 238970 hyperornithinemia, hyperammonemia, homocitrulli- nuria (HHH) 25 222700 lysinuric protein intolerance 26 258870 gyrate atrophy, B6 responsive or non responsive 27 238700 hyperlysinemia (alpha-aminoadipic semialdehyde synthase deficiency) 28 238300-330-310 non ketotic hyperglycinaemia 29 234500 hartnup disorder 30 601815-172480