DOCSLIB.ORG

Involvements of Hyperhomocysteinemia in Neurological Disorders

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Involvements of Hyperhomocysteinemia in Neurological Disorders H OH metabolites OH Review Involvements of Hyperhomocysteinemia in Neurological Disorders Marika Cordaro 1,† , Rosalba Siracusa 2,† , Roberta Fusco 2 , Salvatore Cuzzocrea 2,3,* , Rosanna Di Paola 2,* and Daniela Impellizzeri 2 1 Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; [email protected] 2 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; [email protected] (R.S.); [email protected] (R.F.); [email protected] (D.I.) 3 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA * Correspondence: [email protected] (S.C.); [email protected] (R.D.P.); Tel.: +39-090-6765208 (S.C. & R.D.P.) † The authors equally contributed to the review. Abstract: Homocysteine (HCY), a physiological amino acid formed when proteins break down, leads to a pathological condition called hyperhomocysteinemia (HHCY), when it is over a definite limit. It is well known that an increase in HCY levels in blood, can contribute to arterial damage and several cardiovascular disease, but the knowledge about the relationship between HCY and brain disorders is very poor. Recent studies demonstrated that an alteration in HCY metabolism or a deficiency in folate or vitamin B12 can cause altered methylation and/or redox potentials, that leads to a modification on calcium influx in cells, or into an accumulation in amyloid and/or tau protein involving a cascade of events that culminate in apoptosis, and, in the worst conditions, neuronal death. The present review will thus summarize how much is known about the possible role of HHCY in neurodegenerative disease. Citation: Cordaro, M.; Siracusa, R.; Keywords: homocysteine; hyperhomocysteinemia; target; physiology; pathology Fusco, R.; Cuzzocrea, S.; Di Paola, R.; Impellizzeri, D. Involvements of Hyperhomocysteinemia in Neurological Disorders. Metabolites 1. Introduction 2021, 11, 37. https://doi.org/ Homocysteine (HCY) is a sulfhydryl-containing amino acid produced following the 10.3390/metabo11010037 demethylation of methionine, an amino acid contained primarily in animal protein. To recondition methionine, HCY is recuperated using a pathway that requires folic acid and Received: 27 November 2020 vitamins B6/B12 [1]. Pathologically high blood levels of HCY, indicated as hyperhomocys- Accepted: 1 January 2021 teinemia (HHCY), signal a breakdown in this biochemical process, resulting in biochemical Published: 6 January 2021 and life consequences [2]. Variations in HCY metabolism can also be developed with certain dietary and lifestyle modifications such as increased coffee drinking, cigarette smoking, and Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional clai- alcohol abuse, as these interfere with methionine synthase activity [2]. Until today, HHCY ms in published maps and institutio- has been epidemiologically and clinically correlated in a variety of pathological conditions nal affiliations. and was confirmed also as an independent risk factor for many different pathologies such as cardiovascular disease, neural tube defects, osteoporosis, neuropsychiatric disorders and many, many, others [3–23]. Recent evidence, additionally, related high levels of HCY as a factor that contributes to the development of certain cancers [24–26]. Considering the Copyright: © 2021 by the authors. Li- literature, most of the information of HHCY-related pathologies were focused on cardio- censee MDPI, Basel, Switzerland. vascular disease but less was analyzed for brain disorder. With these aims in mind, we This article is an open access article studied the recent literature of HHCY and brain disorders. distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Metabolites 2021, 11, 37. https://doi.org/10.3390/metabo11010037 https://www.mdpi.com/journal/metabolites Metabolites 2021, 11, x FOR PEER REVIEW 2 of 20 2. Physiological Role of Homocysteine 2.1. Cycle HCY is a physiological metabolite of the essential amino acid methionine (Figure 1). Considering that nutriment contains little or no HCY, nearly all of the HCY in the body is derived from the methionine contained in animal and plant proteins [27,28]. Metabolites 2021, 11, 37x FOR PEER REVIEW 2 2of of 20 19 2.2. Physiological Physiological Role Role of of Homocysteine Homocysteine 2.1.2.1. Cycle Cycle HCYHCY is is a a physiological metabolite metabolite of of the the essential essential amino amino acid acid methionine methionine (Figure (Figure 11).). ConsideringConsidering that nutriment contains little or no HCY, nearly all of the HCY in the body is derivedderived from the methionine contained in animal and plant proteins [[27,28].27,28]. Methionine Homocysteine Figure 1. Chemical structure of methionine and homocysteine. The cycle of HCY is composed by two different pathways that intersect with each other in two points during transsulfuration (Figure 2) and remethylation (Figure 3). During the transsulfuration pathway, HCY condenses with serine to form cystathionine in a non-reversible reaction catalyzed by the pyridoxal-5′-phosphate (PLP)- containing enzyme, cystathionine β-synthase. In the next step, cystathionine is γ α hydrolyzedMethionine by a second PLP-containing Homocysteine enzyme, -cystathionase, to form cysteine and - ketobutyrate. Cysteine, in surplus, is oxidized to taurine or inorganic sulfates or is FigureFigure 1. ChemicalChemical structure structure of methionine and homocysteine. excreted in the urine. Consequently, in addition to the physiological synthesis of cysteine, this transsulfurationTheThe cycle of pathway HCY is effectivelycomposed bycatabolizes two differentdiffer excessent pathways HCY, which that is intersect not required with each for methylotherother in transfer. two points during transsulfuration (Figure 2 2)) andand remethylationremethylation (Figure(Figure3 ).3). During the transsulfuration pathway, HCY condenses with serine to form cystathionine in a non-reversible reaction catalyzed by the pyridoxal-5′-phosphate (PLP)- containing enzyme, cystathionine β-synthase. In the next step, cystathionine is hydrolyzed by a second PLP-containing enzyme, γ-cystathionase, to form cysteine and α- ketobutyrate. Cysteine, in surplus, is oxidized to taurine or inorganic sulfates or is excreted in the urine. Consequently, in addition to the physiological synthesis of cysteine, this transsulfuration pathway effectively catabolizes excess HCY, which is not required for methyl transfer. FigureFigure 2. Transsulfuration 2. Transsulfuration cycle. The cycle. metabolism The metabolism of HCY (homocysteine) of HCY (homocysteine) is composed is composed by two by two differentdifferent steps. steps. MS—methionine MS—methionine synthase; synthase; MTHFR—methylene MTHFR—methylene tetrahydrofolate tetrahydrofolate reductase; reductase; BHMT— BHMT—betaine HCY methyltransferase; DMG—dimethylglycine; B2—riboflavin; THF— betaine HCY methyltransferase; DMG—dimethylglycine; B2—riboflavin; THF—thetrahydrofolate; thetrahydrofolate; SAM S—adenosyl methionine; SAH S—adenosyl homocysteine. SAM S—adenosyl methionine; SAH S—adenosyl homocysteine. On theDuring other the hand, transsulfuration during remethylation, pathway, HCY HCY, condenses to form with methionine, serine to formacquires cystathion- a methyline group in a non-reversible from N-5-methyltetrahydrofolate reaction catalyzed by or the from pyridoxal-5 betaine.0 -phosphateThis metabolic (PLP)-containing reaction with N-5-methyltetrahydrofolate happens in all tissues and is vitamin B12 dependent; enzyme, cystathionine β-synthase. In the next step, cystathionine is hydrolyzed by a however,second the PLP-containing reaction with betaine enzyme, is restriγ-cystathionase,cted mainly to to the form liver cysteine and is andnot dependentα-ketobutyrate. Figure 2. Transsulfuration cycle. The metabolism of HCY (homocysteine) is composed by two by vitaminCysteine, B12. in The surplus, most ispart oxidized of methionine to taurine is orsuccessively inorganic sulfatesactivated or by is excretedATP to form in the S- urine. adenosylmethioninedifferent steps. MS—methionine (SAM). SAM synthase;have a key MT roHFR—methylenele to donate a tetrahydrofolatemethyl group toreductase; different BHMT—betaineConsequently, inHCY addition methyltransferase; to the physiological DMG—dimethylglycine; synthesis of cysteine, B2—riboflavin; this transsulfuration THF— thetrahydrofolate;pathway effectively SAM catabolizes S—adenosyl excess methionine; HCY, whichSAH S—adenos is not requiredyl homocysteine. for methyl transfer. On the other hand, during remethylation, HCY, to form methionine, acquires a methyl groupOn from the N-5-methyltetrahydrofolateother hand, during remethylation, or from betaine. HCY, Thisto form metabolic methionine, reaction acquires with N-5- a methylmethyltetrahydrofolate group from N-5-methyltetrahydrofolate happens in all tissues and or is from vitamin betaine. B12 dependent; This metabolic however, reaction the withreaction N-5-methyltetrahydrofolate with betaine is restricted mainlyhappens to in the all liver tissues and isand not is dependent vitamin B12 by vitamindependent; B12. however,The most partthe reaction of methionine with betaine is successively is restri activatedcted mainly by ATP to the to formliver S-adenosylmethionineand is not dependent by(SAM). vitamin SAM B12.
Load more

Recommended publications
  • Methionine Synthase Supports Tumor Tetrahydrofolate Pools
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284521; this version posted September 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Methionine synthase supports tumor tetrahydrofolate pools Joshua Z. Wang1,2,#, Jonathan M. Ghergurovich1,3,#, Lifeng Yang1,2, and Joshua D. Rabinowitz1,2,* 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA 2 Department of Chemistry, Princeton University, Princeton, New Jersey, USA 3 Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA # These authors contributed equally to this work. *Corresponding author: Joshua Rabinowitz Department of Chemistry and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Rd, Princeton, NJ 08544, USA Phone: (609) 258-8985; e-mail: [email protected] Conflict of Interest Disclosure: J.D.R. is a paid advisor and stockholder in Kadmon Pharmaceuticals, L.E.A.F. Pharmaceuticals, and Rafael Pharmaceuticals; a paid consultant of Pfizer; a founder, director, and stockholder of Farber Partners and Serien Therapeutics. JDR and JMG are inventors of patents in the area of folate metabolism held by Princeton University. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284521; this version posted September 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Mammalian cells require activated folates to generate nucleotides for growth and division. The most abundant circulating folate species is 5-methyl tetrahydrofolate (5-methyl- THF), which is used to synthesize methionine from homocysteine via the cobalamin-dependent enzyme methionine synthase (MTR).
    [Show full text]
  • Defining Sources of Nutrient Limitation for Tumors By
    Defining sources of nutrient limitation for tumors by Mark Robert Sullivan B.S. Molecular Biology and Chemistry University of Pittsburgh (2013) Submitted to the Department of Biology in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY June 2019 © 2019 Mark R. Sullivan. All rights reserved. The author hereby grants to MIT permission to reproduce and to distribute publicly paper and electronic copies of this thesis document in whole or in part in any medium now known or hereafter created. Signature of Author.......................................................................................................................... Department of Biology April 30, 2019 Certified by ...................................................................................................................................... Matthew G. Vander Heiden Associate Professor of Biology Thesis Supervisor Accepted by...................................................................................................................................... Amy E. Keating Professor of Biology Co-Director, Biology Graduate Committee 1 2 Defining sources of nutrient limitation for tumors by Mark Robert Sullivan Submitted to the Department of Biology on April 30, 2019 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biology ABSTRACT Tumor growth requires that cancer cells accumulate sufficient biomass to grow and divide. To accomplish this, tumor cells must acquire
    [Show full text]
  • Aspartic Acid Agonist, in the Mammalian Striatum
    The Journal of Neuroscience August 1986, 6(8): 2226-2234 /II Vitro Release and Electrophysiological Effects In Situ of Homocysteic Acid, An Endogenous N-Methyl-(D)-aspartic Acid Agonist, in the Mammalian Striatum Kim Quang DO,* Paul L. Herrling,? Peter Streit,* Waldemar A. Turski,“fsl and Michel Cuenod* *Brain Research Institute, University of Zurich, Zurich, Switzerland, and j-Wander Research Institute, Bern, Switzerland A potassium-induced, calcium-dependent release of endogenous fects of microiontophoretically applied (L)-HCA on membrane homocysteic acid (HCA) from rat striatal slices was demonstrat- potential and cortically evoked EPSPsin cat caudate neurons, ed. A precolumn derivatization high-performance liquid chro- and the pharmacologicalspecificity of (L)-HCA in this structure. matography method was developed that allowed quantitative de- termination of sulfur-containing amino acids at the picomole level. Materials and Methods Intracellular recordings from cat caudate neurons during si- Materials multaneous microiontophoretic application of drugs and electri- cal stimulation of the corticocaudate pathway showed that (L> Release HCA evoked a depolarization pattern similar to that induced 4-N,N-Dimethylamino-azobenzene-4’-isotbiocyanate (DABITC) was ob- by %methyl-(D>aspartic acid (NMDA), and both these depo- tained from Fluka (Buchs, CH) and recrystallized in acetone (Merck, larizations could be selectively inhibited by a specific NMDA Darmstadt, FRG). All other solvents used were ofcommercial analytical antagonist, (D)-Z-amino-7-phosphonoheptanoicacid [(D)-AP-~]. grade from Merck or Fluka. The internal standard (D,L)-2-amino-7- A selective antagonismof (rJ-HCA-induced depolarizations by sulfonoheptanoic acid (AS-7) was a generous gift of Dr. J. C. Watkins. (L)-homocysteic acid [(L)-HCA], (L)-cysteine sulfinic acid [(L)-CSA], (L)- (D>AP-~ was confirmed in quantitative experiments with the cysteic acid [(L)-CA], and veratrine were purchased from Sigma (St.
    [Show full text]
  • Treatment Protocol Copyright © 2018 Kostoff Et Al
    Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al PREVENTION AND REVERSAL OF ALZHEIMER'S DISEASE: TREATMENT PROTOCOL by Ronald N. Kostoffa, Alan L. Porterb, Henry. A. Buchtelc (a) Research Affiliate, School of Public Policy, Georgia Institute of Technology, USA (b) Professor Emeritus, School of Public Policy, Georgia Institute of Technology, USA (c) Associate Professor, Department of Psychiatry, University of Michigan, USA KEYWORDS Alzheimer's Disease; Dementia; Text Mining; Literature-Based Discovery; Information Technology; Treatments Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al CITATION TO MONOGRAPH Kostoff RN, Porter AL, Buchtel HA. Prevention and reversal of Alzheimer's disease: treatment protocol. Georgia Institute of Technology. 2018. PDF. https://smartech.gatech.edu/handle/1853/59311 COPYRIGHT AND CREATIVE COMMONS LICENSE COPYRIGHT Copyright © 2018 by Ronald N. Kostoff, Alan L. Porter, Henry A. Buchtel Printed in the United States of America; First Printing, 2018 CREATIVE COMMONS LICENSE This work can be copied and redistributed in any medium or format provided that credit is given to the original author. For more details on the CC BY license, see: http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License<http://creativecommons.org/licenses/by/4.0/>. DISCLAIMERS The views in this monograph are solely those of the authors, and do not represent the views of the Georgia Institute of Technology or the University of Michigan. This monograph is not intended as a substitute for the medical advice of physicians. The reader should regularly consult a physician in matters relating to his/her health and particularly with respect to any symptoms that may require diagnosis or medical attention.
    [Show full text]
  • Endogenous Metabolites: JHU NIMH Center Page 1
    S. No. Amino Acids (AA) 24 L-Homocysteic acid 1 Glutaric acid 25 L-Kynurenine 2 Glycine 26 N-Acetyl-Aspartic acid 3 L-arginine 27 N-Acetyl-L-alanine 4 L-Aspartic acid 28 N-Acetyl-L-phenylalanine 5 L-Glutamine 29 N-Acetylneuraminic acid 6 L-Histidine 30 N-Methyl-L-lysine 7 L-Isoleucine 31 N-Methyl-L-proline 8 L-Leucine 32 NN-Dimethyl Arginine 9 L-Lysine 33 Norepinephrine 10 L-Methionine 34 Phenylacetyl-L-glutamine 11 L-Phenylalanine 35 Pyroglutamic acid 12 L-Proline 36 Sarcosine 13 L-Serine 37 Serotonin 14 L-Tryptophan 38 Stachydrine 15 L-Tyrosine 39 Taurine 40 Urea S. No. AA Metabolites and Conjugates 1 1-Methyl-L-histidine S. No. Carnitine conjugates 2 2-Methyl-N-(4-Methylphenyl)alanine 1 Acetyl-L-carnitine 3 3-Methylindole 2 Butyrylcarnitine 4 3-Methyl-L-histidine 3 Decanoyl-L-carnitine 5 4-Aminohippuric acid 4 Isovalerylcarnitine 6 5-Hydroxylysine 5 Lauroyl-L-carnitine 7 5-Hydroxymethyluracil 6 L-Glutarylcarnitine 8 Alpha-Aspartyl-lysine 7 Linoleoylcarnitine 9 Argininosuccinic acid 8 L-Propionylcarnitine 10 Betaine 9 Myristoyl-L-carnitine 11 Betonicine 10 Octanoylcarnitine 12 Carnitine 11 Oleoyl-L-carnitine 13 Creatine 12 Palmitoyl-L-carnitine 14 Creatinine 13 Stearoyl-L-carnitine 15 Dimethylglycine 16 Dopamine S. No. Krebs Cycle 17 Epinephrine 1 Aconitate 18 Hippuric acid 2 Citrate 19 Homo-L-arginine 3 Ketoglutarate 20 Hydroxykynurenine 4 Malate 21 Indolelactic acid 5 Oxalo acetate 22 L-Alloisoleucine 6 Succinate 23 L-Citrulline 24 L-Cysteine-glutathione disulfide Semi-quantitative analysis of endogenous metabolites: JHU NIMH Center Page 1 25 L-Glutathione, reduced Table 1: Semi-quantitative analysis of endogenous molecules and their derivatives by Liquid Chromatography- Mass Spectrometry (LC-TripleTOF “or” LC-QTRAP).
    [Show full text]
  • Primordial Synthesis of Amines and Amino Acids in a 1958 Miller H2 S
    Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment Eric T. Parkera,1, Henderson J. Cleavesb, Jason P. Dworkinc, Daniel P. Glavinc, Michael Callahanc, Andrew Aubreyd, Antonio Lazcanoe, and Jeffrey L. Badaa,2 aGeosciences Research Division, Scripps Institution of Oceanography, University of California at San Diego, 8615 Kennel Way, La Jolla, CA 92093; bGeophysical Laboratory, Carnegie Institution of Washington, 5251 Broad Branch Road NW, Washington, DC 20015; cNational Aeronautics and Space Administration Goddard Space Flight Center, Solar System Exploration Division, Greenbelt, MD 20771; dNational Aeronautics and Space Administration Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109; and eFacultad de Ciencias, Universidad Nacional Autónoma de México, Apdo. Postal 70-407 Ciudad Universitaria, 04510 Mexico D.F., Mexico Edited by Gerald F. Joyce, The Scripps Research Institute, La Jolla, CA, and approved February 14, 2011 (received for review December 22, 2010) Archived samples from a previously unreported 1958 Stanley Miller known volcanic apparatus were found to contain a wide variety of electric discharge experiment containing hydrogen sulfide (H2S) amino acids and amines, including ornithine, homoserine, methy- were recently discovered and analyzed using high-performance lamine, and ethylamine, many of which had not been reported liquid chromatography and time-of-flight mass spectrometry. We previously in spark discharge experiments (7). The volcanic report here the detection and quantification of primary amine- apparatus differed from Miller’s classic apparatus in that it uti- containing compounds in the original sample residues, which were lized an aspirator that injected steam into the electric discharge produced via spark discharge using a gaseous mixture of H2S, CH4, chamber, simulating a volcanic eruption (1).
    [Show full text]
  • The Controversial Role of Homocysteine in Neurology: from Labs to Clinical Practice
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio istituzionale della ricerca - Università di Trieste International Journal of Molecular Sciences Review The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice Rita Moretti * and Paola Caruso Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, 34149 Trieste, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-040-399-4572 Received: 29 November 2018; Accepted: 4 January 2019; Published: 8 January 2019 Abstract: Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke.
    [Show full text]
  • Amino Acid Disorders
    471 Review Article on Inborn Errors of Metabolism Page 1 of 10 Amino acid disorders Ermal Aliu1, Shibani Kanungo2, Georgianne L. Arnold1 1Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA Contributions: (I) Conception and design: S Kanungo, GL Arnold; (II) Administrative support: S Kanungo; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: E Aliu, GL Arnold; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Georgianne L. Arnold, MD. UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Suite 1200, Pittsburgh, PA 15224, USA. Email: [email protected]. Abstract: Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are “essential” in that they must be ingested in the diet. In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb’s (aka TCA) cycle intermediates and other metabolites, and recycled as needed. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term ‘Inborn Error of Metabolism’ (IEM). The key concept of a single gene defect leading to a single enzyme dysfunction, leading to “intoxication” with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue.
    [Show full text]
  • Recycling of Vitamin B12 and NAD+ Within the Pdu Microcompartment of Salmonella Enterica Shouqiang Cheng Iowa State University
    Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2010 Recycling of vitamin B12 and NAD+ within the Pdu microcompartment of Salmonella enterica Shouqiang Cheng Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Biochemistry, Biophysics, and Structural Biology Commons Recommended Citation Cheng, Shouqiang, "Recycling of vitamin B12 and NAD+ within the Pdu microcompartment of Salmonella enterica" (2010). Graduate Theses and Dissertations. 11713. https://lib.dr.iastate.edu/etd/11713 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. + Recycling of vitamin B12 and NAD within the Pdu microcompartment of Salmonella enterica by Shouqiang Cheng A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Biochemistry Program of Study Committee: Thomas A. Bobik, Major Professor Alan DiSpirito Basil Nikolau Reuben Peters Gregory J. Phillips Iowa State University Ames, Iowa 2010 Copyright © Shouqiang Cheng, 2010. All rights reserved. ii Table of contents Abstract.............................................................................................................................
    [Show full text]
  • Abstracts from the 50Th European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 26:820–1023 https://doi.org/10.1038/s41431-018-0248-6 ABSTRACT Abstracts from the 50th European Society of Human Genetics Conference: Electronic Posters Copenhagen, Denmark, May 27–30, 2017 Published online: 1 October 2018 © European Society of Human Genetics 2018 The ESHG 2017 marks the 50th Anniversary of the first ESHG Conference which took place in Copenhagen in 1967. Additional information about the event may be found on the conference website: https://2017.eshg.org/ Sponsorship: Publication of this supplement is sponsored by the European Society of Human Genetics. All authors were asked to address any potential bias in their abstract and to declare any competing financial interests. These disclosures are listed at the end of each abstract. Contributions of up to EUR 10 000 (ten thousand euros, or equivalent value in kind) per year per company are considered "modest". Contributions above EUR 10 000 per year are considered "significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal and fetal echocardiography. The molecular karyotyping Genetics revealed a gain in 8p11.22-p23.1 region with a size of 27.2 Mb containing 122 OMIM gene and a loss in 8p23.1- E-P01.02 p23.3 region with a size of 6.8 Mb containing 15 OMIM Prenatal diagnosis in a case of 8p inverted gene. The findings were correlated with 8p inverted dupli- duplication deletion syndrome cation deletion syndrome. Conclusion: Our study empha- sizes the importance of using additional molecular O¨. Kırbıyık, K. M. Erdog˘an, O¨.O¨zer Kaya, B. O¨zyılmaz, cytogenetic methods in clinical follow-up of complex Y.
    [Show full text]
  • Congenital Ocular Anomalies in Newborns: a Practical Atlas
    www.jpnim.com Open Access eISSN: 2281-0692 Journal of Pediatric and Neonatal Individualized Medicine 2020;9(2):e090207 doi: 10.7363/090207 Received: 2019 Jul 19; revised: 2019 Jul 23; accepted: 2019 Jul 24; published online: 2020 Sept 04 Mini Atlas Congenital ocular anomalies in newborns: a practical atlas Federico Mecarini1, Vassilios Fanos1,2, Giangiorgio Crisponi1 1Neonatal Intensive Care Unit, Azienda Ospedaliero-Universitaria Cagliari, University of Cagliari, Cagliari, Italy 2Department of Surgery, University of Cagliari, Cagliari, Italy Abstract All newborns should be examined for ocular structural abnormalities, an essential part of the newborn assessment. Early detection of congenital ocular disorders is important to begin appropriate medical or surgical therapy and to prevent visual problems and blindness, which could deeply affect a child’s life. The present review aims to describe the main congenital ocular anomalies in newborns and provide images in order to help the physician in current clinical practice. Keywords Congenital ocular anomalies, newborn, anophthalmia, microphthalmia, aniridia, iris coloboma, glaucoma, blepharoptosis, epibulbar dermoids, eyelid haemangioma, hypertelorism, hypotelorism, ankyloblepharon filiforme adnatum, dacryocystitis, dacryostenosis, blepharophimosis, chemosis, blue sclera, corneal opacity. Corresponding author Federico Mecarini, MD, Neonatal Intensive Care Unit, Azienda Ospedaliero-Universitaria Cagliari, University of Cagliari, Cagliari, Italy; tel.: (+39) 3298343193; e-mail: [email protected].
    [Show full text]
  • Analysis of Body Composition and Nutritional Status in Brazilian Phenylketonuria Patients
    Molecular Genetics and Metabolism Reports 6 (2016) 16–20 Contents lists available at ScienceDirect Molecular Genetics and Metabolism Reports journal homepage: www.elsevier.com/locate/ymgmr Analysis of body composition and nutritional status in Brazilian phenylketonuria patients Priscila Nicolao Mazzola a,b, Tatiele Nalin c,⁎, Kamila Castro d,MargreetvanRijnb, Terry G.J. Derks b, Ingrid D.S. Perry e, Alberto Scofano Mainieri f, Ida Vanessa D. Schwartz c,g,h a Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2600 anexo, 90035-003, Porto Alegre, Brazil b Beatrix Children's Hospital, Section of Metabolic Diseases, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands c Post-Graduation Program in Genetics and Molecular Biology, UFRGS, Bento Gonçalves 9500/43323M, PO Box 15053, Porto Alegre, Brazil d Postgraduate Program in Pediatrics and Adolescent Health, UFRGS, Ramiro Barcelos 2400, 90035-003, Porto Alegre, Brazil e Postgraduate Program in Collective Health, Health Unit, Universidade do Extremo Sul Catarinense, Universitária 1105, 88806-000 Criciúma, Brazil f Department of Pediatrics, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2400, 90035-003 Porto Alegre, Brazil g Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil h Department of Genetics, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil article info abstract Article history: Background: Phenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to Received 20 November 2015 the low activity of phenylalanine-hydroxylase.
    [Show full text]