DOCSLIB.ORG

Amino Acids and N-Acetyl-Aspartyl-Glutamate As Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Amino Acids and N-Acetyl-Aspartyl-Glutamate As Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 1989 Amino Acids and N-acetyl-aspartyl-glutamate as Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways Ricardo A. Molinar-Rode Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/1641 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. These are also available as one exposure on a standard 35mm slide or as a 17" x 23" black and white photographic print for an additional charge. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information Com pany 300 North Z eeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 9000716 Amino acids and N-acetyl-aspartyl-glutamate as neurotransmitter candidates in the monkey retinogeniculate pathways Molinar-Rode, Ricardo A., Ph.D. City University of New York, 1989 UMI 300 N. ZeebRd. Ann Arbor, MI 48106 ■lLL.jtjm m im ,Liii--LiiijL. 11 jiibii. pm.k.i ■ AMINO ACIDS AND N-ACETYL-ASPARTYL-GLUTAMATE AS NEUROTRANSMITTER CANDIDATES IN THE MONKEY RETINOGENICULATE PATHWAYS by Ricardo A. Molinar-Rode A dissertation submitted to the Graduate Faculty in Biomedical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York. 1989 This manuscript has been read and accepted for the Graduate Faculty in Biomedical Sciences in satisfaction of the dissertation requirement for the degree of Doctor of Philosophy. [signature] <2./* 3/ W Date ChairmarPof the Examining Committee Pedro Pasik, M.D. [signature] X f'lT.U'S Dat a ' Terry Krulwich, Ph.D. Bernard Cohen, M.D. Soil Berl, M.D. Andreas Plaitakis, M.D. Efrain Azmitia, Ph.D. Supervisory Committee The City University of New York ABSTRACT AMINO ACIDS AND N-ACETYL-ASPARTYL-GLUTAMATE AS NEUROTRANSMITTER CANDIDATES IN THE MONKEY RETINOGENICULATE PATHWAYS by Ricardo A. Molinar-Rode Advisor: Professor Pedro Pasik The lateral geniculate nucleus (LGNd) receives chemically identified inputs from brain stem structures, the thalamus and visual cortex. The identity of the neurotransmitter(s) in the retinal input, however, is unknown. To investigate the possibility that some amino acids and certain dipeptides, such as N-acetyl-aspartyl-glutamate (NAAG), fulfill this function, changes in their concentration were measured in the optic tract, parvocellular and magno- cellular segments of the LGNd, superior colliculus and visual cortex of six monkeys (Macaca fascicularis) , seven days after right optic tractotomy. The LGNd was studied also in two additional macaques, three months after occipital lobectomy. Tissue was frozen within five minutes of death, regions were dissected with the micropunch technique, and substances were analyzed by HPLC. Of the ten compounds measured in the normal side, gluta­ mate, glutamine, glycine, and alanine had homogeneous distri­ butions. GABA was highest in the superior colliculus, cysta­ thionine and NAAG decreased in the rostrocaudal direction, and N-acetyl-aspartate showed an opposite gradient of concentra­ tion. The heterogeneity in taurine and aspartate was less systematic. Optic tract section induced significant, large reductions in NAAG, glutamate and aspartate in the optic tract distal to the lesion. Significant decreases in NAAG, and to a lesser extent in glutamate, were observed in the LGNd. Changes in the dipeptide were apparent in both the parvocellular and magnocellular segments. Reductions in glutamate reached significance in the parvocellular laminae, and those of aspartate approached significance in the magnocellular division. No significant differences were detected in the superior colliculus and striate cortex. Occipital lobectomy produced large declines in aspartate and glutamate in the LGNd, as well as moderate reductions in alanine and GABA, and minor changes in glutamine and glycine. The results of optic tractotomy support the role of NAAG as a neurotransmitter candidate in the monkey retinogeniculate pathways; its significant decrease in both geniculate segments suggests that X- and Y- retinal axons utilize this substance. Although at times the reductions in glutamate or aspartate failed to reach significance, their role cannot be excluded. The findings after occipital lobectomy strongly favor these latter substances as corticogeniculate transmitters. ACKNOWLEDGEMENTS I wish to express my appreciation to: Dr. Pedro Pasik, my advisor, for his consistent guidance throughout the course of this project, and for his exceptional advice in writing this manuscript. The members of my supervisory committee, for their interest in my work and important suggestions. I thank especially Dr. Soli Berl, for his support and scientific counsel, and Dr. Andreas Plaitakis, for his advice in biochemical methods. I extend my gratitude to the members of the Neurology Department, in particular to Dr. Catherine Mytilineou, for her support at some difficult moments. Dr. Terry Krulwich, and the organizers of the Doctoral Program in Neurobiology, for giving me the opportunity to accomplish my education in this exciting field. Drs. Andrew Glover, Gay Holstein and Julian Martinez, for fruitful discussions, and for helping to maintain an enthu­ siastic, supportive working environment. Victor Rodriguez and Rosemary Lang, for their technical assistance, and expertise in photography. The members of the Clinical Trials Unit at Mount Sinai, for their friendship, assistance, and for introducing me to the use of WordPerfect and some graphics programs. My family, friends and especially Liliana, for their love and support. v TABLE OF CONTENTS Title page i Approval page ii Abstract iii Acknowledgements V Table of contents vi List of tables ix List of figures X I. INTRODUCTION 1 II. BACKGROUND 4 1. MORPHOLOGICAL FEATURES OF THE MONKEY DORSAL LATERAL GENICULATE NUCLEUS 4 1.1 NORMAL STRUCTURE 4 1.2 DEGENERATIVE CHANGES 14 2. NEUROACTIVE SUBSTANCES IN THE LATERAL GENICULATE NUCLEUS 21 2.1 AMINO ACIDS 21 A) GLUTAMATE AND ASPARTATE 21 B) GABA 38 C) GLYCINE 47 2.2 PEPTIDES 49 A) SUBSTANCE P 49 B) ENKEPHALIN 52 C) CHOLECYSTOKININ 53 D) SOMATOSTATIN 55 E) OTHERS 57 2.3 ACETYLCHOLINE 62 2.4 MONOAMINES 68 A) SEROTONIN 68 B) NORADRENALINE 72 C) ADRENALINE 76 vi D) DOPAMINE 77 III. MATERIALS AND METHODS 79 1. SUBJECTS 79 2. PROCEDURES 79 2.1 SURGERY 79 2.1.1 RIGHT OPTIC TRACT SECTION 79 2.1.2 LEFT OCCIPITAL LOBECTOMY 84 2.2 NEUROLOGICAL EXAMINATION 85 2.3 SPECIMEN COLLECTION 88 2.4 HISTOLOGY 90 2.5 TISSUE PREPARATION 90 2.6 BIOCHEMICAL ANALYSES 101 2.6.1 AMINO ACID ANALYSIS 101 2.6.2 NASP AND NAAG ANALYSIS 108 2.7 STATISTICAL ANALYSES 111 2.7.1 CONTROL (NORMAL) STRUCTURES 111 2.7.2 CONTROL AGAINST EXPERIMENTAL STRUCTURES 112 IV. RESULTS 114 1. NEUROLOGICAL EXAMINATION 114 1.1 RIGHT OPTIC TRACTOTOMY 114 1.2 LEFT OCCIPITAL LOBECTOMY 115 2. HISTOLOGICAL VERIFICATION 115 2.1 RIGHT OPTIC TRACTOTOMY 115 2.2 LEFT OCCIPITAL LOBECTOMY 116 3. BIOCHEMICAL ANALYSES 121 3.1 AMINO ACID ANALYSIS 121 3.1.1 CRITERIA FOR EXCLUSION/INCLUSION 121 3.1.2 NORMAL REGIONAL DISTRIBUTION 12 6 3.1.3 EFFECTS OF LESIONS 139 A) OPTIC TRACT SECTION 139 B) OCCIPITAL LOBECTOMY 151 vii 3.2 NAAG AND NASP ANALYSIS 153 3.2.1 NORMAL REGIONAL DISTRIBUTION 153 3.2.2 EFFECTS OF OPTIC TRACT SECTION 163 V. DISCUSSION 169 VI. REFERENCES 191 viii LIST OF TABLES Amino acid concentration in the visual system 23 Glutamate-related binding in the visual system 33 Substance-P concentration in the visual system 51 Experimental subjects 80 Amounts of tissue collected for analyses 98 HPLC gradient program for amino acid analysis 102 Fluorescence constants for some amino acids 123 Normal regional distribution of amino acids in the monkey visual system 130 Effect of optic tractotomy on the amino acid concentration in the monkey visual system 141 Effect of occipital lobectomy on the amino acid concentration in the lateral geniculate nucleus 152 Normal
Load more

Recommended publications
  • Hydroxylation of the Eukaryotic Ribosomal Decoding Center Affects Translational Accuracy
    Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy Christoph Loenarza,1, Rok Sekirnika,2, Armin Thalhammera,2, Wei Gea, Ekaterina Spivakovskya, Mukram M. Mackeena,b,3, Michael A. McDonougha, Matthew E. Cockmanc, Benedikt M. Kesslerb, Peter J. Ratcliffec, Alexander Wolfa,4, and Christopher J. Schofielda,1 aChemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom; bTarget Discovery Institute, University of Oxford, Oxford OX3 7FZ, United Kingdom; and cCentre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom Edited by William G. Kaelin, Jr., Harvard Medical School, Boston, MA, and approved January 24, 2014 (received for review July 31, 2013) The mechanisms by which gene expression is regulated by oxygen Enzyme-catalyzed hydroxylation of intracellularly localized are of considerable interest from basic science and therapeutic proteins was once thought to be rare, but accumulating recent perspectives. Using mass spectrometric analyses of Saccharomyces evidence suggests it is widespread (11). Motivated by these cerevisiae ribosomes, we found that the amino acid residue in findings, we investigated whether the translation of mRNA to closest proximity to the decoding center, Pro-64 of the 40S subunit protein is affected by oxygen-dependent modifications. A rapidly ribosomal protein Rps23p (RPS23 Pro-62 in humans) undergoes growing eukaryotic cell devotes most of its resources to the tran- posttranslational hydroxylation. We identify RPS23 hydroxylases scription, splicing, and transport of ribosomal proteins and rRNA as a highly conserved eukaryotic subfamily of Fe(II) and 2-oxoglu- (12). We therefore reasoned that ribosomal modification is a tarate dependent oxygenases; their catalytic domain is closely re- candidate mechanism for the regulation of protein expression.
    [Show full text]
  • Significance of Urinary Hydroxyproline in Man
    SIGNIFICANCE OF URINARY HYDROXYPROLINE IN MAN Darwin J. Prockop, Albert Sjoerdsma J Clin Invest. 1961;40(5):843-849. https://doi.org/10.1172/JCI104318. Find the latest version: https://jci.me/104318/pdf SIGNIFICANCE OF URINARY HYDROXYPROLINE IN MAN By DARWIN J. PROCKOP AND ALBERT SJOERDSMA (From the Section of Experimental Therapeutics, National Heart Institute, Bethesda, Md.) (Submitted for publication September 27, 1960; accepted January 12, 1961) Since nearly all of the hydroxyproline of the of Marfan's syndrome (2) reflect a rapid rate of body is found in collagen, it has been suggested collagen degradation. (1, 2) that the urinary excretion of this imino An incidental discovery in the study was that acid may be an important index of collagen me- the increase in urinary hydroxyproline after in- tabolism. The origin of urinary hydroxyproline, gestion of gelatin represents an increased excre- however, is not definitely established. The iso- tion of hydroxyproline peptides. This appears to topic studies of Stetten (3) in rats indirectly sug- be the first demonstration that significant amounts gested that most of the free and peptide hydroxy- of peptides can be excreted following ingestion of proline in the body arises from the breakdown of a protein. collagen, since she found that hydroxyproline-N'5 was not significantly incorporated into collagen. MATERIALS AND METHODS Ziff, Kibrick, Dresner and Gribetz (1), on the The 8 subjects utilized in the study were hospitalized other hand, observed an increased excretion of for periods of 3 to 12 weeks; 3 were patients with Mar- hydroxyproline when it was added to the diet of fan's syndrome, 2 of whom were previously shown to have elevated excretions of hydroxyproline (2).
    [Show full text]
  • GABA Receptors
    D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43.
    [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]
  • (12) Patent Application Publication (10) Pub. No.: US 2007/0254315 A1 Cox Et Al
    US 20070254315A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0254315 A1 Cox et al. (43) Pub. Date: Nov. 1, 2007 (54) SCREENING FOR NEUROTOXIC AMINO (60) Provisional application No. 60/494.686, filed on Aug. ACID ASSOCATED WITH NEUROLOGICAL 12, 2003. DSORDERS Publication Classification (75) Inventors: Paul A. Cox, Provo, UT (US); Sandra A. Banack, Fullerton, CA (US); Susan (51) Int. Cl. J. Murch, Cambridge (CA) GOIN 33/566 (2006.01) GOIN 33/567 (2006.01) Correspondence Address: (52) U.S. Cl. ............................................................ 435/721 PILLSBURY WINTHROP SHAW PITTMAN LLP (57) ABSTRACT ATTENTION: DOCKETING DEPARTMENT Methods for screening for neurological disorders are dis P.O BOX 105OO closed. Specifically, methods are disclosed for screening for McLean, VA 22102 (US) neurological disorders in a Subject by analyzing a tissue sample obtained from the subject for the presence of (73) Assignee: THE INSTITUTE FOR ETHNO elevated levels of neurotoxic amino acids or neurotoxic MEDICINE, Provo, UT derivatives thereof associated with neurological disorders. In particular, methods are disclosed for diagnosing a neu (21) Appl. No.: 11/760,668 rological disorder in a subject, or predicting the likelihood of developing a neurological disorder in a Subject, by deter (22) Filed: Jun. 8, 2007 mining the levels of B-N-methylamino-L-alanine (BMAA) Related U.S. Application Data in a tissue sample obtained from the subject. Methods for screening for environmental factors associated with neuro (63) Continuation of application No. 10/731,411, filed on logical disorders are disclosed. Methods for inhibiting, treat Dec. 8, 2003, now Pat. No. 7,256,002.
    [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]
  • 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.
    [Show full text]
  • Chemical Methods for the Characterization of Proteolysis in Cheese During Ripening Plh Mcsweeney, Pf Fox
    Chemical methods for the characterization of proteolysis in cheese during ripening Plh Mcsweeney, Pf Fox To cite this version: Plh Mcsweeney, Pf Fox. Chemical methods for the characterization of proteolysis in cheese during ripening. Le Lait, INRA Editions, 1997, 77 (1), pp.41-76. hal-00929515 HAL Id: hal-00929515 https://hal.archives-ouvertes.fr/hal-00929515 Submitted on 1 Jan 1997 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Lait (1997) 77, 41-76 41 © ElseviernNRA Review Chemical methods for the characterization of proteolysis in cheese during ripening PLH McSweeney, PF Fox Department of Food Chemistry, University College, Cork, Ireland Summary - Proteolysis is the principal and most complex biochemical event which occurs during the maturation of most cheese varieties. Proteolysis has been the subject of much study and a range of analytieal techniques has been developed to assess its extent and nature. Methods for assessing pro- teolysis can he c1assified under two broad headings: non-specifie and specifie techniques, both of which are reviewed. Non-specifie techniques include the quantitation of nitrogen soluble in various extrac- tants or precipitants and the Iiberation of reactive groups.
    [Show full text]
  • Designing Peptidomimetics
    CORE Metadata, citation and similar papers at core.ac.uk Provided by UPCommons. Portal del coneixement obert de la UPC DESIGNING PEPTIDOMIMETICS Juan J. Perez Dept. of Chemical Engineering ETS d’Enginyeria Industrial Av. Diagonal, 647 08028 Barcelona, Spain 1 Abstract The concept of a peptidomimetic was coined about forty years ago. Since then, an enormous effort and interest has been devoted to mimic the properties of peptides with small molecules or pseudopeptides. The present report aims to review different approaches described in the past to succeed in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry approach, where parts of the peptide are successively replaced by non-peptide moieties until getting a non-peptide molecule and a biophysical approach, where a hypothesis of the bioactive form of the peptide is sketched and peptidomimetics are designed based on hanging the appropriate chemical moieties on diverse scaffolds. Although both approaches have been used in the past, the former has been more widely used to design peptidomimetics of secretory peptides, whereas the latter is nowadays getting momentum with the recent interest in designing protein-protein interaction inhibitors. The present report summarizes the relevance of the information gathered from structure-activity studies, together with a short review on the strategies used to design new peptide analogs and surrogates. In a following section there is a short discussion on the characterization of the bioactive conformation of a peptide, to continue describing the process of designing conformationally constrained analogs producing first and second generation peptidomimetics. Finally, there is a section devoted to review the use of organic scaffolds to design peptidomimetics based on the information available on the bioactive conformation of the peptide.
    [Show full text]
  • Interpretive Guide for Amino Acids
    Interpretive Guide for Amino Acids Intervention Options LOW HIGH Essential Amino Acids Arginine (Arg) Arg Mn Histidine (His) Folate, His Isoleucine (Ile) * B6, Check for insulin insensitivity Leucine (Leu) * B6, Check for insulin insensitivity Lysine (Lys) Carnitine Vitamin C, Niacin, B6, Iron, a-KG Methionine(Met) * B6, á-KG, Mg, SAM Phenylalanine (Phe) * Iron,VitaminC,Niacin,LowPhediet Threonine(Thr) * B6, Zn Tryptophan(Trp) Trpor5-HTP Niacin, B6 Valine (Val) * B6, Check for insulin insensitivity Essential Amino Acid Derivatives Neuroendocrine Metabolism y-Aminobutyric Acid (GABA) a-KG, B6 Glycine (Gly) Gly Folate, B6,B2,B5 Serine (Ser) B6, Mn, Folate * Taurine (Tau) Tau, B6 Vit. E, Vit. C, B-Carotene, CoQ10, Lipoate Tyrosine(Tyr) Iron,Tyr,VitaminC,Niacin Cu, Iron, Vitamin C, B6 Ammonia/Energy Metabolism a-Aminoadipic Acid B6, a-KG Asparagine (Asn) Mg Aspartic Acid (Asp) a-KG, B6 Mg, Zn Citrulline (Cit) Mg, Aspartic acid Glutamic Acid (Glu) B6, a-KG Niacin, B6 Glutamine (Gln) a-KG, B6 Ornithine (Orn) Arg Mg, a-KG, B6 Sulfur Metabolism Cystine (Cys) NAC B2 Cystathionine B6 Homocystine (HCys) B6, Folate, B12, Betaine Additional Metabolites a-Amino-N-Butyric Acid a-KG, B6 B6, a-KG Alanine (Ala) * B6 Anserine Zn n-Alanine Lactobacillus and Bifidobacteria, B6 n-Aminoisobutyric Acid B6 Carnosine Zn Ethanolamine Mg Hydroxylysine (HLys) Vitamin C, Iron, a-KG Hydroxyproline (HPro) Vitamin C, Iron, a-KG 1-Methylhistidine Vitamin E, B12, Folate 3-Methylhistidine BCAAs, Vit. E, Vit. C, n-Carotene, CoQ10, Lipoate Phosphoethanolamine (PE) SAM, B12, Folate, Betaine Phosphoserine Mg Proline (Pro) a-KG Vitamin C, Niacin Sarcosine B2 * Use balanced or custom mixtures of essential amino acids Nordic Laboratiroes∙ Nygade 6, 3.sal ∙ 1164 Copenhagen K ∙ DenmarkTel: +45 33 75 1000 ∙ e-mail: [email protected] In association with ©Metametrix, Inc.
    [Show full text]
  • Ratio of Phosphate to Amino Acids
    National Institute for Health and Care Excellence Final Neonatal parenteral nutrition [D10] Ratio of phosphate to amino acids NICE guideline NG154 Evidence reviews February 2020 Final These evidence reviews were developed by the National Guideline Alliance which is part of the Royal College of Obstetricians and Gynaecologists FINAL Error! No text of specified style in document. Disclaimer The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian. Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties. NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive.
    [Show full text]