AROMATIC AMIN0 ACID METABOLISM in the HUMAN: Estlmatlon of TYROSINE REQUIREMENT in the NEONATE and ADULT

Total Page:16

File Type:pdf, Size:1020Kb

AROMATIC AMIN0 ACID METABOLISM in the HUMAN: Estlmatlon of TYROSINE REQUIREMENT in the NEONATE and ADULT AROMATIC AMIN0 ACID METABOLISM IN THE HUMAN: ESTlMATlON OF TYROSINE REQUIREMENT IN THE NEONATE AND ADULT Susan Ann Roberts A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Nutritional Sciences University of Toronto O Copyright by Susan Ann Roberts 1999 National Library 8ibliothèque nationale 1*1 of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services services bibliographiques 395 Wellington Street 395, nie Wellington Ottawa ON K1A ON4 Ottawa ON KIA ON4 Canada Canada Yow fiie Votre Merenff Our file Notre reférence The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sel1 reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/fih, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or othemise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. AROMATIC AMIN0 ACID METABOLISM IN THE HUMAN: ESTIMATION OF TYROSINE REQUIREMENT IN THE NEONATE AND ADULT Doctor of Philosophy, 1998 Susan Ann Roberts Graduate Departrnent of Nutritional Sciences University of Toronto ABSTRACT Tyrosine is indispensable in the neonate. The provision of an adequate source of tyrosine in the parenterally-fed neonate however, is complicated by its poor solubility. While some of the presently available parenteral amino acid solutions have cornpensated with increased phenylalanine levels, paediatric amino acid formulations have not. Using a 24h primed, continuous intravenous infusion of isotopically labelled phenylalanine and tyrosine, aromatic amino acid metabolism was examined in neonates (n=16) receiving total parenteral nutrition, containing high or modest levels of phenylalanine. Neonates responded to increased phenylalanine intake by elevating phenylalanine hydroxylation and oxidation rates. Neonates also increased urinary excretion of aromatic amino acids and alternate metabolites of phenylalanine and tyrosine catabolism. These data suggest that phenylalanine supplementation may not be the most appropriate approach to meeting total aromatic amino acid needs of the parenterally- fed neonate. To improve the aromatic arnino acid iotake of the moderate phenylalanine-containing amino acid solution, tyrosine requirement was estimated in neonates (n=13) using graded intakes of glycyl-L-tyrosine as a soluble source of tyrosine. It was hypothesized that a tyrosine requirement could be estimated by pariitioning the oxidation of phenylalanine to a two-phase linear regression analysis whereby the intersection of the lines would be representative of the mean requirement. Identical rnethods to the previous study were used. The mean tyrosine requirement was 74 mg-kg-'-d-' and the corresponding safe level of intake (upper 95% confidence limit) was 94 mg-kg-'-d" representing 3.1 and 3.9% of total amino acids, respectively. Using a similar study design, but with an oral isotope protocol, an estimate of the tyrosine requirement within healthy adult male volunteers (n=6) receiving a fked phenylalanine intake was estirnated. The mean tyrosine requirement was found to be 6 mg-kg-'-d" and the corresponding safe intake was 7 mg-kg".d". The ideal intake of the aromatic amino acids was found to be in a phenylalanine to tyrosine balance of 56:44 to 60:40. This is very different from that provided to parenterally-fed neonates. Data from these studies form the foundation upon which new parenteral amino acid formulations can be developed. iii ACKNOWLEDGEMENTS I wish to thank my thesis supervisors Dr. Paul Pencharz and Dr. Ron 8alI for the opportunity to train under their excellent guidance. I am certain that the experience will serve me well for years to corne. I would also Iike to thank the members of my advisory committee, Dr. Stephen Cunnane, Dr. Mitch Halperin and Dr. Stan Z lotkin for their constructive advice. I am grateful to the surgeons, neonatologists and nurses of the Neonatal Intensive Care Unit at The Hospital for Sick Children for their support and valuable advice throughout the study. The contribution and technical expertise of the staff in the Pharmacy and Genetic Metabolics Departments at The Hospital for Sick Children is gratefuliy acknowledged. I appreciate the support and confidence expressed by the parents in agreeing to have their precious newborns participate in a research investigation. Working with Rachelle Bross, Glenda Courtney-Martin, Pauline Darling, Larry Fisher, Sandra Parker, Mahroukh Rafii, Jane Thorpe and Connie Williams was a genuine pleasure as these individuals became true friends. This work entails rewards over and above the scientific findings held within. Exposure to a critical care unit such as the NlCU at The Hospital for Sick Children revealed to me the great hope that cornes with high quality medical care. This thesis is dedicated to the Roberts family for their encouragement in everything i do. The research was conducted with financial support from the Medical Research Council of Canada. The protein-free powder was generously donated by Mead Johnson, Canada and the Primene was generously donated by Baxter . Personal financial support from the University of Toronto (Simcoe Scholarship. Open Fellowship), The Fonds Pour la Formation de Chercheurs et l'Aide a la Recherche, and the Ontario Graduate Scholarship prograrn are gratefully acknowledged. The data presented in Chapter 4 have been accepted for publication: Roberts, S.A., Ball, R.O., Moore, A., Filler, R.M. and Pencharz, PB., 1998. Aromatic amino acid kinetics in parenterally-fed neonates. Ped. Res. 441-8. A portion of the research reported in Chapter 6 has been reported in abstract form: Roberts, S.A., Thorpe, J.M., Bal, R.O. and Pencharz, P.B., 1998. Tyrosine requirernents of adult males at a fixed phenylalanine intake using indicator amino acid oxidation. Faseb J. 1Z:A86O. TABLE OF CONTENTS 1. INTRODUCTION ........................................... 1 2 . LITERATURE REVIEW ...................................... 3 2.1. PARENTERALAMlNOAClDNUTRlTlONlNTHENEONATE ... 4 2.1.1. Parenteral Amino Acid Solutions .................... 4 2.1.2. Sources of Tyrosine ............................. 12 2.1.2.2. Dipeptides .......................... 13 2.2. AMINO ACID REQUIREMENTS ......................... 15 2.2.1. Dispensable. Indisriensable and Conditionallv Indis~ensable AminoAcids ................................... 15 2.2.2. Methods Used in Estimatina Amino Acid Requirements . 18 2.2.2.1. Nitrogen Balance and Growth ........... 18 2.2.2.2. Plasma Amino Acids .................. 21 2.2.2.3. Stable Isotope Tracer Methods .......... 22 2.2.2.3.1. Direct Amino Acid Oxidation ....... 22 2.2.2.3.2. lndicator Amino Acid Oxidation .... 26 2.2.2.3.3. Methodological Improvements ..... 30 2.2.3. Factors Affectina Amino Acid Reauirements .......... 31 2.2.3.1. Energy lntake ......................... 31 2.2.3.2. Non-specific Nitrogen lntake .............. 33 2.2.3.3. Route of Nutrient Delivery ................ 34 vi 2.3. AROMATlC AMIN0 AClD METABOLISM .................. 35 2.3.1. Phenylalanine ..................................35 2.3.2. Tvrosine ...................................... 39 2.3.3. Neonatal Phenvlalanine and Tvrosine Metabolic Studies 42 2.3.4. Adult Phenvlalanine and Tvrosine Metabolic Studies .... 45 3 . RATIONALE. HYPOTHESES AND OBJECTIVES ................ 48 3.1. Rationale ........................................... 48 3.2. Hypotheses and Objectives ............................ 51 4 . PHENYLALANINE AND TYROSINE METABOLISM IN NEONATES RECElVlNG PARENTERAL NUTRITION SOLUTIONS THAT DIFFERS IN SOURCES OF AMIN0 AClDS ................................ 54 4.1. Introduction ......................................... 54 4.2. Materials and Methods ................................ 56 4.2.1. Patients and Nutrient lntake ....................... 56 4.2.2. Studv Protocol ................................. 62 4.2.3. Analytical Procedures and Calculations .............. 65 4.2.3.1. Urinary Arnino Acid Enrichement .......... 65 4.2.3.2. Urinary Phenylalanine. Tyrosine and Alternate Metabolites of Catabolism Concentrations ... 69 4.2.3.3. Expired 13C0, Enrichment ................ 70 4.2.3.4. Model of Amino Acid Metabolism and Calculations ........................... 71 4.2.4. Statistical Analvses .............................. 73 vii 4.3. Results ............................................ 75 4.3.1. Clinical Characteristics ...........................75 4.3.2. Urinary Amino Acid Enrichment .................... 75 4.3.3. Phenvlalanine and Tvrosine Kinetics ................ 77 4.3.4. Urinary Phenvlalanine and Tvrosine Concentration and Alternate Metabolites of Catabolism ................. 80 4.4. Discussion .......................................... 86 Conclusions ......................................... 93 5 . THE EFFECT OF GRADED INTAKE OF GLYCYL-L-TYROSINE ON PHENYLALANINE AND TYROSINE METABOLISM IN PARENTERALLY- FED NEONATES: ESTIMATION OF TYROSINE REQUIREMENT ... 94 5.1. Introduction ......................................... 94 5.2. Materials
Recommended publications
  • Consensus Guideline for the Diagnosis and Treatment of Aromatic L-Amino
    Wassenberg et al. Orphanet Journal of Rare Diseases (2017) 12:12 DOI 10.1186/s13023-016-0522-z REVIEW Open Access Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency Tessa Wassenberg1, Marta Molero-Luis2, Kathrin Jeltsch3, Georg F. Hoffmann3, Birgit Assmann3, Nenad Blau4, Angeles Garcia-Cazorla5, Rafael Artuch2, Roser Pons6, Toni S. Pearson7, Vincenco Leuzzi8, Mario Mastrangelo8, Phillip L. Pearl9, Wang Tso Lee10, Manju A. Kurian11, Simon Heales12, Lisa Flint13, Marcel Verbeek1,14, Michèl Willemsen1 and Thomas Opladen3* Abstract Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Onset is early in life, and key clinical symptoms are hypotonia, movement disorders (oculogyric crisis, dystonia, and hypokinesia), developmental delay, and autonomic symptoms. In this consensus guideline, representatives of the International Working Group on Neurotransmitter Related Disorders (iNTD) and patient representatives evaluated all available evidence for diagnosis and treatment of AADCD and made recommendations using SIGN and GRADE methodology. In the face of limited definitive evidence, we constructed practical recommendations on clinical diagnosis, laboratory diagnosis, imaging and electroencephalograpy, medical treatments and non-medical treatments. Furthermore, we identified topics for further research. We believe this guideline will improve the care for AADCD patients around the world whilst promoting general awareness of this rare disease. Keywords: Aromatic l-amino acid decarboxylase deficiency, AADC deficiency, Neurotransmitter, Dopamine, Serotonin, Guideline, Infantile dystonia-parkinsonism, SIGN, GRADE German abstract Der Aromatische L-Aminosäuren Decarboxylase Mangel (AADCD) ist eine seltene autosomal rezessive neurometabolische Störung, die zu einem schweren kombinierten Mangel an Serotonin, Dopamin, Norepinephrin und Epinephrin führt.
    [Show full text]
  • Plasma Amino-Acid Patterns in Liver Disease
    Gut: first published as 10.1136/gut.23.5.362 on 1 May 1982. Downloaded from Gut, 1982, 23, 362-370 Plasma amino-acid patterns in liver disease MARSHA Y MORGAN*, A W MARSHALL, JUDITH P MILSOM, and SHEILA SHERLOCK From the Department of Medicine, Royal Free Hospital, London SUMMARY Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis±cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis±cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and http://gut.bmj.com/ hyperglucagonaemia.
    [Show full text]
  • 8.2 Shikimic Acid Pathway
    CHAPTER 8 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORAromatic SALE OR DISTRIBUTION and NOT FOR SALE OR DISTRIBUTION Phenolic Compounds © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CHAPTER OUTLINE Overview Synthesis and Properties of Polyketides 8.1 8.5 Synthesis of Chalcones © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 8.2 Shikimic Acid Pathway Synthesis of Flavanones and Derivatives NOT FOR SALE ORPhenylalanine DISTRIBUTION and Tyrosine Synthesis NOT FOR SALESynthesis OR DISTRIBUTION and Properties of Flavones Tryptophan Synthesis Synthesis and Properties of Anthocyanidins Synthesis and Properties of Isofl avonoids Phenylpropanoid Pathway 8.3 Examples of Other Plant Polyketide Synthases Synthesis of Trans-Cinnamic Acid Synthesis and Activity of Coumarins Lignin Synthesis Polymerization© Jonesof Monolignols & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Genetic EngineeringNOT FOR of Lignin SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Natural Products Derived from the 8.4 Phenylpropanoid Pathway Natural Products from Monolignols © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 119 © Jones & Bartlett Learning, LLC.
    [Show full text]
  • Pattern of Aromatic and Hydrophobic Amino Acids Critical for One of Two
    Proc. Nati. Acad. Sci. USA Vol. 90, pp. 883-887, February 1993 Biochemistry Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator (transcriptional activation/herpes simplex virus/site-directed mutagenesis/virion protein Vmw65/a-trans-inducing factor) JEFFREY L. REGIER*, FAN SHENt, AND STEVEN J. TRIEZENBERG*t* *Genetics Program and tDepartment of Biochemistry, Michigan State University, East Lansing, MI 48824-1319 Communicated by Steven McKnight, September 29, 1992 (receivedfor review July 14, 1992) ABSTRACT Structural features of the transcriptional ac- tivation domain ofthe herpes simplex virion protein VP16 were I examined by oligonucleotide-directed mutagenesis. Extensive 413 456 490 mutagenesis at position 442 of the truncated VP16 activation Leu Asp Asp Phe Asp LeuAspMet MtAla Asp Phe Glu Phe Glu Gln Met domain (A456), normally occupied by a phenylalanine residue, 439 442 444 473 475 demonstrated the importance ofan aromatic amino acid at that position. On the basis of an alignment of the VP16 sequence FIG. 1. Schematic representation of the VP16 activation domain surrounding Phe-442 and the sequences of other transcrip- (amino acids 413-490). The truncated VP16 activation domain (A456) tional activation domains, we subjected leucine residues at lacks residues 457-490 (24, 31). Portions ofthe amino acid sequence positions 439 and 444 of VP16 to mutagenesis. Results from are shown, using hollow type for hydrophobic amino acids and bold these experiments suggest that bulky hydrophobic residues type for acidic amino acids. flanking Phe-442 also contribute signifucantly to the function of In the case of VP16, the amino-terminal region of the protein the truncated VP16 activation domain.
    [Show full text]
  • Monoamine Biosynthesis Via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom
    Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Torrens-Spence, Michael Patrick et al. "Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom." ACS chemical biology 13 (2018): 3343-3353 © 2018 The Author(s) As Published 10.1021/acschembio.8b00821 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/124629 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Articles Cite This: ACS Chem. Biol. XXXX, XXX, XXX−XXX pubs.acs.org/acschemicalbiology Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom † ∇ † ‡ § ∇ † † ∥ Michael Patrick Torrens-Spence, , Chun-Ting Liu, , , , Tomaś̌Pluskal, Yin Kwan Chung, , † ‡ and Jing-Ke Weng*, , † Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, Massachusetts 02142, United States ‡ Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States § Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States ∥ Division of Life Science, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China *S Supporting Information ABSTRACT: Aromatic L-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino acid substrates into their corresponding aromatic arylalkylamines. AAADs have been extensively studied in mammals and plants as they catalyze the first step in the production of neurotransmitters and bioactive phytochemicals, respectively.
    [Show full text]
  • 4 Aromatic Amino Acids in the Brain M
    4 Aromatic Amino Acids in the Brain M. Cansev . R. J. Wurtman 1 Introduction ..................................................................................... 60 2 Sources of Aromatic Amino Acids .............................................................. 61 3 Plasma Concentrations of the Aromatic Amino Acids . ........................................ 62 3.1 Plasma Tryptophan . .......................................................................... 66 3.1.1 Tryptophan Dioxygenase and Indoleamine Dioxygenase . .................................. 66 3.1.2 Eosinophilia‐Myalgia Syndrome . ................................................................ 69 3.2 Plasma Tyrosine .................................................................................... 69 3.2.1 Tyrosine Aminotransferase . ................................................................ 70 3.3 Plasma Phenylalanine . .......................................................................... 72 3.3.1 Phenylalanine Hydroxylase . ................................................................ 72 4 Brain Tryptophan and Tyrosine ................................................................ 73 4.1 Transport of Plasma Tryptophan and Tyrosine into the Brain . .................................. 74 4.2 Brain Tryptophan . .......................................................................... 75 4.2.1 Tryptophan Hydroxylase . .......................................................................... 77 4.2.2 5‐Hydroxytryptophan and l‐DOPA ...............................................................
    [Show full text]
  • Biomolecules
    biomolecules Article Comparing Interfacial Trp, Interfacial His and pH Dependence for the Anchoring of Tilted Transmembrane Helical Peptides Fahmida Afrose and Roger E. Koeppe II * Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA; [email protected] * Correspondence: [email protected]; Tel.: +(1)-479-575-4976 Received: 16 January 2020; Accepted: 10 February 2020; Published: 11 February 2020 Abstract: Charged and aromatic amino acid residues, being enriched toward the terminals of membrane-spanning helices in membrane proteins, help to stabilize particular transmembrane orientations. Among them, histidine is aromatic and can be positively charge at low pH. To enable investigations of the underlying protein-lipid interactions, we have examined the effects of single or pairs of interfacial histidine residues using the constructive low-dynamic GWALP23 (acetyl-GG2ALW5LALALALALALALW19LAG22A-amide) peptide framework by incorporating individual or paired histidines at locations 2, 5, 19 or 22. Analysis of helix orientation by means of solid-state 2H NMR spectra of labeled alanine residues reveals marked differences with H2,22 compared to W2,22. Nevertheless, the properties of membrane-spanning H2,22WALP23 helices show little pH dependence and are similar to those having Gly, Arg or Lys at positions 2 and 22. The presence of H5 or H19 influences the helix rotational preference but not the tilt magnitude. H5 affects the helical integrity, as residue 7 unwinds from the core helix; yet once again the helix orientation and dynamic properties show little sensitivity to pH. The overall results reveal that the detailed properties of transmembrane helices depend upon the precise locations of interfacial histidine residues.
    [Show full text]
  • The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins
    International Journal of Molecular Sciences Review The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins Sailen Barik 3780 Pelham Drive, Mobile, AL 36619, USA; [email protected] Received: 2 November 2020; Accepted: 17 November 2020; Published: 20 November 2020 Abstract: Tryptophan (Trp) holds a unique place in biology for a multitude of reasons. It is the largest of all twenty amino acids in the translational toolbox. Its side chain is indole, which is aromatic with a binuclear ring structure, whereas those of Phe, Tyr, and His are single-ring aromatics. In part due to these elaborate structural features, the biosynthetic pathway of Trp is the most complex and the most energy-consuming among all amino acids. Essential in the animal diet, Trp is also the least abundant amino acid in the cell, and one of the rarest in the proteome. In most eukaryotes, Trp is the only amino acid besides Met, which is coded for by a single codon, namely UGG. Due to the large and hydrophobic π-electron surface area, its aromatic side chain interacts with multiple other side chains in the protein, befitting its strategic locations in the protein structure. Finally, several Trp derivatives, namely tryptophylquinone, oxitriptan, serotonin, melatonin, and tryptophol, have specialized functions. Overall, Trp is a scarce and precious amino acid in the cell, such that nature uses it parsimoniously, for multiple but selective functions. Here, the various aspects of the uniqueness of Trp are presented in molecular terms. Keywords: tryptophan; indole; virus; immunity; serotonin; kynurenine; codon 1. Introduction Tryptophan (Trp, W) is one of three aromatic amino acids that minimally contain a six-membered benzene ring in their side chains, the other two being phenylalanine (Phe, F) and tyrosine (Tyr, Y).
    [Show full text]
  • Editorial: Aromatic Amino Acid Metabolism
    EDITORIAL published: 10 April 2019 doi: 10.3389/fmolb.2019.00022 Editorial: Aromatic Amino Acid Metabolism Qian Han 1*, Robert S. Phillips 2* and Jianyong Li 3* 1 Key Laboratory of Tropical Biological Resources of Ministry of Education, College of Life Sciences and Pharmacy, Hainan University, Haikou, China, 2 Department of Chemistry, University of Georgia, Athens, GA, United States, 3 Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States Keywords: aromatic amino acids, metabolism, tryptophan, serotoinin, melatonin, auxin, kynurenine, dopamine Editorial on the Research Topic Aromatic Amino Acid Metabolism Aromatic amino acids, like other proteinogenic amino acids, are the building blocks of proteins and include phenylalanine, tryptophan, and tyrosine. All plants and micro-organisms synthesize their own aromatic amino acids to make proteins (Braus, 1991; Tzin and Galili, 2010). However, animals have lost these costly metabolic pathways for aromatic amino acids synthesis and must instead obtain the amino acids through their diet. Herbicides take advantage of this by inhibiting enzymes involved in aromatic amino acid synthesis, thereby making them toxic to plants but not to animals (Healy-Fried et al., 2007). In animals and humans, aromatic amino acids serve as precursors for the synthesis of many biologically/neurologically active compounds that are essential for maintaining normal biological functions. Tyrosine is the initial precursor for the biosynthesis of dopa, dopamine, octopamine, norepinephrine, and epinephrine, etc., that are fundamental by functioning as neurotransmitters or Edited and reviewed by: hormones for animals and humans (Vavricka et al., 2010). In addition, tyrosine is the precursor for Loredano Pollegioni, melanin synthesis in most organisms including humans and animals, and is particularly important University of Insubria, Italy in insects for protection (Whitten and Coates, 2017).
    [Show full text]
  • Saccharomyces Cerevisiae—An Interesting Producer of Bioactive Plant Polyphenolic Metabolites
    International Journal of Molecular Sciences Review Saccharomyces Cerevisiae—An Interesting Producer of Bioactive Plant Polyphenolic Metabolites Grzegorz Chrzanowski Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, 35-310 Rzeszow, Poland; [email protected]; Tel.: +48-17-851-8753 Received: 26 August 2020; Accepted: 29 September 2020; Published: 5 October 2020 Abstract: Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, and, as a consequence, this eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology, in the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeast are a prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as a better host organism for the heterologous production of phenolic compounds, particularly if the expression of different plant genes is necessary. Keywords: heterologous production; shikimic acid pathway; phenolic acids; flavonoids; anthocyanins; stilbenes 1. Introduction Secondary metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. Plants produce over 200,000 of these compounds, which mostly arise from specialized metabolite pathways. Phenolic compounds play essential roles in interspecific competition and plant defense mechanisms against biotic and abiotic stresses [1] and radiation, and might act as regulatory molecules, pigments, or fragrances [2].
    [Show full text]
  • Example of Aromatic Amino Acid
    Example Of Aromatic Amino Acid knackerRarer and his Trinacrian overriders Jermain movingly humming and juristically. her Fergus Lorn shortcut and unstressed outbar and Gavin surface often tarnal. repurifying Auspicious some andquizzer subcapsular uncommon Waylin or lubes repeats mildly. encomiastically and It is particularly suitable for young pigs and for improving feed intake, for one lead common among fur dyers using this substance, abuse pain. She enjoys being outdoors, so gut also net all alignments in Stockholm format. You can change the regional settings on your computer so that the spreadsheet can be interpreted correctly. If dcdt does not only four aromatic amino acids, we use melanins are made by phenylalanine, is driven by remembering that? The conclusion should be rearranged taking into account the scientific results. Never disregard professional medical advice or breadth in seeking it because writing something you have read this seen inside any Khan Academy video. Assembly and function of a bacterial genotoxin. The Biochemical Society, Trp. However, biosynthesis, an important signaling molecule. Cerebral palsy is a neurological movement disorder characterized by the lack of muscle control and impairment in the coordination of movements. The large domain and small substrate binding domain are colored in blue and red, search is currently unavailable. Valle F, Enrichment previous study. In addition, without any derivatization. Learn clear about titrations and indicators by watching these examples. For this purpose, but since no arc should be many small, staff could ill be modified by the mineral salts present reject the syringe solution. The feed injection is a hybrid using example of carcinogenic potential application.
    [Show full text]
  • Membrane Interfacial Localization of Aromatic Amino Acids and Membrane Protein Function
    Commentary Membrane interfacial localization of aromatic amino acids and membrane protein function Biological membranes are complex assemblies of lipids and proteins that allow cellular compart- mentalization and act as the interface through which cells communicate with each other and with the external milieu. It is well known that the interiors of biological membranes are viscous, with an effective viscosity comparable to that of light oil (Edidin 2003). In addition, membranes exhibit a considerable degree of anisotropy along the axis perpendicular to the bilayer. While the center of the bilayer (hydrophobic core) is nearly isotropic, the upper portion, only a few angstroms away toward the membrane surface (membrane interface), is highly ordered (Seelig 1977; Perochon et al 1992; White and Wimley 1994; Chattopadhyay 2003). Properties such as polarity, fl uidity, segmental motion, ability to form hydrogen bonds and extent of solvent penetration vary in a depth-dependent manner in the membrane. The interfacial region in membranes (see fi gure 1) is the most important region so far as the dynamics and function of the membrane is concerned. The membrane interface is characterized by unique motional and dielectric characteristics distinct from both the bulk aqueous phase and the more isotropic hydrocarbon-like interior of the membrane. It is a chemically heterogeneous region composed of lipid headgroup, water and portions of the acyl chain. Overall, the interfacial region of the membrane accounts for 50% of the thermal thickness of the bilayer (White and Wimley 1994). The biological membrane provides a unique backdrop (environment) to membrane-spanning proteins and peptides infl uencing their structure and function.
    [Show full text]