List of 116 Targeted Metabolites
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University Microfilms International 300 N
INFORMATION TO USERS This was produced from a copy of a document sent to us for microfilming. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help you understand markings or notations which may appear on this reproduction. 1. The sign or "target” for pages apparently lacking from the document photographed is "Missing Page(s)”. If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure you of complete continuity. 2. When an image on the film is obliterated with a round black mark it is an indication that the film inspector noticed either blurred copy because of movement during exposure, or duplicate copy. Unless we meant to delete copyrighted materials that should not have been filmed, you will find a good image of the page in the adjacent frame. If copyrighted materials were deleted you will find a target note listing the pages in the adjacent frame. 3. When a map, drawing or chart, etc., is part of the material being photo graphed the photographer has followed a definite method in “sectioning” the material. It is customary to begin filming at the upper left hand corner of a large sheet and to continue from left to right in equal sections with small overlaps. If necessary, sectioning is continued again—beginning below the first row and continuing on until complete. -
Separation and Quantitation of Water Soluble Cellular Metabolites by Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry Sunil U
Journal of Chromatography A, 1125 (2006) 76–88 Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry Sunil U. Bajad a, Wenyun Lu a, Elizabeth H. Kimball a, Jie Yuan a, Celeste Peterson b, Joshua D. Rabinowitz a,∗ a Lewis-Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, NJ 08544, USA b Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA Received 13 January 2006; received in revised form 8 May 2006; accepted 10 May 2006 Available online 6 June 2006 Abstract A key unmet need in metabolomics is the ability to efficiently quantify a large number of known cellular metabolites. Here we present a liquid chromatography (LC)–electrospray ionization tandem mass spectrometry (ESI-MS/MS) method for reliable measurement of 141 metabolites, including components of central carbon, amino acid, and nucleotide metabolism. The selected LC approach, hydrophilic interaction chromatography with an amino column, effectively separates highly water soluble metabolites that fail to retain using standard reversed-phase chromatography. MS/MS detection is achieved by scanning through numerous selected reaction monitoring events on a triple quadrupole instrument. When applied to extracts of Escherichia coli grown in [12C]- versus [13C]glucose, the method reveals appropriate 12C- and 13C-peaks for 79 different metabolites. © 2006 Elsevier B.V. All rights reserved. Keywords: LC–ESI-MS/MS; Escherichia coli; Metabolomics; Metabonomics; Hydrophilic interaction chromatography; Bacteria; Metabolite; metabolism; Triple quadrupole; Mass spectrometry 1. Introduction pounds, likely capture most key metabolic end products and intermediates [5–8]. Thus, a key current need is an assay that The ability to quantify numerous mRNA in parallel using can reliably and efficiently measure these known compounds DNA microarrays has revolutionized biological science, with [9]. -
S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure
nutrients Article S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure Anna Maria Czarnecka , Wojciech Hilgier and Magdalena Zieli ´nska* Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawi´nskiego Street, 02-106 Warsaw, Poland; [email protected] (A.M.C.); [email protected] (W.H.) * Correspondence: [email protected]; Tel.: +48-22-6086470; Fax: +48-22-6086442 Received: 11 June 2020; Accepted: 15 July 2020; Published: 17 July 2020 Abstract: Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis is regulated by cysteine synthesized from homocysteine via the transsulfuration pathway present in the brain. The transsulfuration-transmethylation interdependence is controlled by a methyl group donor, S-adenosylmethionine (AdoMet) conversion to S-adenosylhomocysteine (AdoHcy), whose removal by subsequent hydrolysis to homocysteine counteract AdoHcy accumulation-induced OS and excitotoxicity. Methods: Rats received three consecutive intraperitoneal injections of thioacetamide (TAA) at 24 h intervals. We measured AdoMet and AdoHcy concentrations by HPLC-FD, glutathione (GSH/GSSG) ratio (Quantification kit). Results: AdoMet/AdoHcy ratio was reduced in the brain but not in the liver. The total glutathione level and GSH/GSSG ratio, decreased in TAA rats, were restored by AdoMet treatment. Conclusion: Data indicate that disturbance of redox homeostasis caused by AdoHcy in the TAA rat brain may represent a deleterious mechanism of brain damage in HE. -
Human Metabolome Technologies
Human Metabolome Human Metabolome Technologies Inc. (HMT) is a leading metabolomics service provider company established on July 2003 based on capillary electrophoresis mass spectrometry (CE-MS) technologies. Technologies The company was listed on the Mothers section of Tokyo Stock Exchange in December 2013. Our main Commissioned metabolome analysis services business is commissioned metabolomics analysis using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS): We have a time-tested track record in a number of different fields including medical sciences, pharmaceuticals, food products, fermentation, and cosmetics. With an aim of contributing in a wide range of fields, we will now set our sights on untapped areas such as the environment, energy, and chemical industries. History Jul 2003 Founded in Suehiromachi in Tsuruoka, Yamagata Prefecture with capital of 10 million yen. Jun 2004 Concluded a joint research agreement with Ajinomoto Co., Inc. May 2009 Commenced the “HMT Research Grant for Young Leaders” Aug 2012 Launched a cancer research specialized package, “C-SCOPE.” Oct 2012 Established a sales subsidiary, “Human Metabolome Technologies America, Inc.” in Massachusetts, USA Sep 2013 Registered the patent “The biomarker for depression, the measuring method for the biomarker of depression, and the program and storage for the diagnostic method” (patent number 5372213) in Japan Dec 2013 Listed on the Mothers section of the Tokyo Stock Exchange Jan 2016 Established a biomarker business company “HMT Biomedical Co., Ltd.” in Yokohama, Kanagawa, Japan May 2017 Established a sales subsidiary, “Human Metabolome Technologies Europe B.V.” in Leiden, Netherlands Apr 2018 Launched functional lipidomics specialized package “Mediator Scan” Human Metabolome Technologies Inc. -
Integrating Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry and Parallel Two-Dimensional Liquid Chromatograph
Electronic Supplementary Material (ESI) for Analyst. This journal is © The Royal Society of Chemistry 2019 Integrating Comprehensive Two-dimensional Gas Chromatography Mass Spectrometry and Parallel Two-dimensional Liquid Chromatography Mass Spectrometry for Untargeted Metabolomics Md Aminul Islam Prodhan1,2,3,4, Biyun Shi1,4, Ming Song2,3,6, Liqing He1,2,3,4, Fang Yuan1,2,3,4, Xinmin Yin1,4, Patrick Bohman8 , Craig McClain2,3,5,6,7, Xiang Zhang1,2,3,4,5 1Department of Chemistry, 2University of Louisville Alcohol Research Center, 3University of Louisville Hepatobiology & Toxicology Program, 4Center for Regulatory and Environmental Analytical Metabolomics, 5 Department of Pharmacology & Toxicology, 6 Department of Medicine, University of Louisville, Louisville, KY 40208, USA,7Robley Rex Louisville VAMC, Louisville, Kentucky 40292, USA, 8Thermo Fisher Scientific International Inc., 3000 Lakeside Dr., Bannockburn, IL, 60015, USA *CORRESPONDING AUTHOR Prof. Xiang Zhang, Department of Chemistry, University of Louisville, 2210 South Brook Street, Louisville, KY 40208, USA. Phone: +01 502 852 8878. Fax: +01 502 852 8149. E-mail: [email protected]. 1 Figure S1. Two compounds co-eluted from the first dimension GC but separated by the second dimension GC. (A) is a three-dimensional view, and (B) is a contour plot. 2 Table S1. Data processing parameters used in LECO ChromaTOF software Data processing parameters used in LECO ChromaTOF. Baseline Offset 1 Number of Data Points Averaged for Baseline Auto Smoothing Peak Width for Peak Finding -
Biological Chemistry Department
MINISTRY OF HEALTH OF UKRAINE ZAPORIZHZHIA STATE MEDICAL UNIVERSITY Biological Chemistry Department Biological chemistry A manual for independent work at home and in class preparation for licensing examination “KROK 1” on semantic modules 6, 7 of module 2 for students of International Faculty (the second year of study) Zaporizhzhia 2017 UDC 577.1(075) BBC 28.902я73 B60 Ratified on meeting of the Central methodical committee of Zaporozhye State Medical University (protocol N 3 from 02_03_17) and it is recommended for the use in educational process for foreign students. Reviewers: Prihodko O. B., Head of Department of Medical Biology, Parasitology and Genetics. Dr. Hab, assoc. professor; Belenichev I. F., Head of Department of Pharmacology and Medicinal Preparations, Dr. Hab., professor Authors: Aleksandrova K. V., Romanenko M. I., Krisanova N. V., Ivanchenko D. G., Rudko N. P., Levich S. V. Biological chemistry : a manual for independent work at home and in class preparation for licensing examination "KROK 1" on semantic modules 6, 7 of module 2 for students of International Faculty (the second year of study) / K. V. Aleksandrova, М. І. Romanenko, N. V. Krisanova, D. G. Ivanchenko, N. P. Rudko, S. V. Levich. – Zaporizhzhia : ZSMU, 2017. – 213 p. This manual is recommended for II year students of International Faculty of specialty "General medicine" studying biological chemistry, as additional material to prepare for practical training semantic modules 6, 7 of module 2 and licensing exam "KROK 1: General medical training". Біологічна хімія : навч.-метод. посіб. для самостійної роботи при підготовці до ліцензійного іспиту "КРОК 1" змістових модулів 6, 7 модулю 2 для студентів 2 курсу міжнар. -
Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes
antioxidants Review Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes Gethin J. McBean School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland; [email protected]; Tel.: +353-1-716-6770 Received: 13 July 2017; Accepted: 1 August 2017; Published: 3 August 2017 Abstract: This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of thiol-containing amino acid metabolism on the antioxidant capacity of astrocytes is also discussed. − Keywords: cysteine; cystine; cysteamine; cystathionine; glutathione; xc cystine-glutamate exchanger; transsulfuration 1. Introduction Thiol groups, whether contained within small molecules, peptides, or proteins, are highly reactive and prone to spontaneous oxidation. Free cysteine readily oxidises to its corresponding disulfide, cystine, that together form the cysteine/cystine redox couple. Similarly, the tripeptide glutathione (γ-glutamyl-cysteinyl-glycine) exists in both reduced (GSH) and oxidised (glutathione disulfide; GSSG) forms, depending on the oxidation state of the sulfur atom on the cysteine residue. In the case of proteins, the free sulfhydryl group on cysteines can adopt a number of oxidation states, ranging from disulfides (–S–S–) and sulfenic acids (–SOOH), which are reversible, to the more oxidised sulfinic (–SOO2H) and sulfonic acids (–SOO3H), which are not. These latter species may arise as a result of chronic and/or severe oxidative stress, and generally indicate a loss of function of irreversibly oxidised proteins. Methionine residues oxidise to the corresponding sulfoxide, which can be rescued enzymatically by methionine sulfoxide reductase [1]. -
The Biosynthesis of Cystathionine in Patients with Homocystinuria
Pediat. Res. 2: 149-160 (1968) Cystathionase homoserine cystathionine pyridoxine cystine serine homocystinuria The Biosynthesis of Cystathionine in Patients with Homocystinuria P.W.K.WONG[30], V.SCHWARZ and G.M.KOMROWER Department of Medical Biochemistry, University of Manchester, and the Mental Retardation Unit, Royal Manchester Children's Hospital, Manchester, England Extract The synthesis in rat and normal human liver homogenates of cystathionine from homoserine +cysteine was studied. When cystathionine was used as substrate, cyst(e)ine was formed and incubation of liver homogenate with homoserine-(-cysteine resulted in the formation of cystathionine. Incubation of homogenate prepared from homocystinuric hVer with L-homoserine+DL-cysteine- 3-14G or DL-cysteine-35S resulted in the formation of labelled cystathionine. The identity of cystathio- nine was established in three chromatographic separations. Oral loading with homoserine and cysteine or cystine in two patients with homocystinuria resulted in urinary excretion of cystathionine in amounts similar to that reported in normal human subjects without amino acid loading. Speculation The observation that human and monkey brains contain much larger quantities of cystathionine than those of other species [26] suggests a special relation of this amino acid to the normal development and function of the primate brain. Cystathionine is either absent from or markedly deficient in the brain of untreated homocystinuric patients [2, 9]. Since we have shown that synthesis of cystathionine from homoserine and cysteine does take place in the patient's liver in vitro, supplementation of the diet with homoserine and cysteine may prove effective in raising intracellular cystathionine concentration to- ward the normal, and may possibly improve the prognosis in this disease. -
Title: Homocystinuria Caused by Cystathionine Β-Synthase Deficiency Genereview — Terms Used to Describe Sulfur Amino Acids Au
Title: Homocystinuria Caused by Cystathionine β-Synthase Deficiency GeneReview — Terms Used to Describe Sulfur Amino Acids Authors: Sacharow SJ, Picker JD, Levy HL Updated: May 2017 Terms Used to Describe Sulfur Amino Acids Note: The terms used to describe the sulfur amino acids are confusing because homocysteine, the thiol within the methionine metabolic pathway (Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency; see Figure 1) with its free sulfur, readily combines with other thiols (such as another homocysteine or cysteine) to form a disulfide; it is primarily the disulfides that are measured in the standard amino acid analysis. For clarity, Mudd et al [2000] have proposed the following terminology to describe the sulfur amino acid metabolites that are important in homocystinuria and related disorders: Homocysteine (HcyH). A thiol compound: Homocystine (Hcy-Hcy). A symmetric disulfide: Homocysteine-cysteine mixed disulfide (Hcy-Cys). An asymmetric disulfide: Total homocysteine (tHcy). All of the Hcy that is present, including that which is bound to protein, most of which is liberated from disulfide bonding by a specific analysis that requires prior reduction. Total free homocysteine (tfHcy). A measurement sometimes used in following individuals with homocystinuria, calculated by assigning two Hcy's to the amount of free homocystine (Hcy-Hcy), one Hcy to the amount of homocysteine-cysteine mixed disulfide (Hcy-Cys), and adding the amounts. Total free Hcy is distinguished from tHcy, which includes the Hcy that was formerly protein bound. References Mudd SH, Finkelstein JD, Refsum H, Ueland PM, Malinow MR, Lentz SR, Jacobsen DW, Brattstrom L, Wilcken B, Wilcken DE, Blom HJ, Stabler SP, Allen RH, Selhub J, Rosenberg IH. -
Human Metabolome Technologies
Human Metabolome Technologies メタ ボ ロ ーム 受 託 解 析 サ ービス ヒ ュー マ ン・メタ ボ ロ ー ム・テ クノ ロ ジ ー ズ 株 式 会 社 取扱店 本社研究所 〒997-0052 山形県鶴岡市覚岸寺水上246-2 東京事務所 〒104-0033 東京都中央区新川2丁目9-6 シュテルン中央ビル5階 TEL:03-3551-2180 FAX:03-3551-2181 MAIL:[email protected] 201710Ver.2 Who are We? What is CE-MS? ヒ ューマン・メタ ボ ロ ー ム・テ クノ ロ ジ ーズ 株 式 会 社(H M T )は、CE-MS法(次ページ参照)の HMTでは、生体内の代謝物質の多くがイオン性 CE-MS 水溶 性イオン性 物 質 技術をもとに2003年7月に設立された、メタボロミクス のリー ディン グ カン パ ニ ーで す 。 の低分子であることに着目し、イオン性低分子の 核酸 糖リン酸 リン酸 体 物 質 2013年12月には東証マザーズに上場いたし 測定に適したキャピラリー電気泳動(Capillary 糖代謝物 有機酸 アミノ酸 ました。 主な事業内容はCE-TOFMSを利用 Electrophoresis, CE)と質量分析計(Mass アミノ酸 分 解 物 ポリアミン したメタボロ ー ム 受 託 解 析 で 、医科 学・製 薬・ Spectromer, MS)を組み合わせた分析技術で 食 品・発 酵・化 粧 品 など 様 々な 分 野 に お い て あるCE-MS法を基盤 LC-MS 脂溶性中性物質 実績をあげています。今後は環境、エネル 技 術 と し 、分 析 お よ び 脂質 脂肪酸 アシルカルニチン ギ ー 、化 学 な ど の 分 野 も 視 野 に 入 れ 、幅 広 い 分 析 法 の 開 発 を行 って 胆汁酸 ポリフェノール ステロイド 分 野で の 貢 献を目 指しています 。 います。 Metabolome Analysis 製 薬 What is Metabolomics? 薬 理・薬 効 毒 性・安 全 性 コンパニオン診 断 生 体 内 に は 核 酸( D N A , R N A )や タ ン パ ク 質 の ほ か に 、糖 、有 機 酸 、ア ミ ノ 酸 な ど の 低 分 子 が マーカー (CDx) 発 酵・生 産 化粧品 農 学 存在しています。これらの物質の多くは、酵素などの代謝反応によって作り出された代謝 品種改良 生産効率向上 安全性評価 生産性向上 物質(メタボライト)です。メタボロミクスとは「代謝物質の種類や濃度を網羅的に分析・解 機能解明 成分効果評価 生態の解明 析する手法」のことです。 化 学 診 断 環 境 の 変 化 や 薬 物 摂 取 、食事 、様々な 疾 患 へ の 羅 患 など に より 、血液・尿・組 織・細 胞 など バイオ燃 料 診断薬開発 バイオリファイナリー 治療効果評価 に存在する代謝物質の種類や濃度に変化が起こります。その変化を分析することにより、 食 品 バイオマーカーの探索、薬剤や機能性成分の作用機序解明、遺伝子変異や発現の変化に 食品分析 機能性食品評価 伴 う 代 謝 へ の 影 響 など を 評 価・考 察 す る こと が 可 能 と な りま す 。 新規機能性成分の 探索 02 HMT HMT 03 極 限 のコストパ フォーマンスモ デル 解析対象 報告書例 CE-TOFMS 約900 定 量 Basic Scan -
Fundamentals of Medicinal Chemistry
Fundamentals of Medicinal Chemistry Gareth Thomas University of Portsmouth, UK Fundamentals of Medicinal Chemistry Fundamentals of Medicinal Chemistry Gareth Thomas University of Portsmouth, UK Copyright # 2003 by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England National 01243 779777 International (þ44) 1243 779777 e-mail (for orders and customer service enquiries): [email protected] Visit our Home Page on http://www.wiley.co.uk or http://www.wiley.com All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London, UK W1P 9 HE, without the permission in writing of the publisher. Other Wiley Editorial Offices John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158–0012, USA Wiley-VCH Verlag GmbH, Pappelallee 3, D-69469 Weinheim, Germany John Wiley & Sons (Australia) Ltd, 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02–01, Jin Xing Distripark, Singapore 0512 John Wiley & Sons (Canada) Ltd, 22 Worcester Road, Rexdale, Ontario M9W 1L1, Canada Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books Library of Congress Cataloging-in-Publication Data Thomas, Gareth, Dr. Fundamentals of medicinal chemistry / Gareth Thomas. p. cm. -
Homocystinuria Due to Cystathionine Β-Synthase Deficiency
Homocystinuria due to cystathionine β-synthase deficiency Author: Doctor Sufin Yap1 Creation Date: May 2003 Update: February 2005 Scientific Editor: Professor Jean-Marie Saudubray 1National Centre for Inherited Metabolic Disorders, The Childrens University Hospital and Our Ladys Hospital for Sick Children, Temple Street, Crumlin, Dublin 1, Dublin. [email protected] Abstract Keywords Disease name Synonyms Diagnosis criteria/Definition Homocysteine nomenclature Incidence Clinical description Differential diagnosis Management and treatment Diagnosis and diagnostic methods Molecular diagnosis Antenatal diagnosis Clinical outcome-Effect of chronic treatment References Abstract Classical homocystinuria due to cystathionine beta-synthase (CbS) deficiency is an autosomal recessively inherited disorder of methionine metabolism. Cystathionine beta-synthase is an enzyme that converts homocysteine to cystathionine in the trans-sulphuration pathway of the methionine cycle and requires pyridoxal 5-phosphate as a cofactor. The other two cofactors involved in remethylation pathway of methionine include vitamin B12 and folic acid. According to the data collected from countries that have screened over 200,000 newborns, the current cumulative detection rate of CbS deficiency is 1 in 344,000. In several individual areas, the reported incidence is much higher. Classical homocystinuria is accompanied by an abundance and variety of clinical and pathological abnormalities, which show major involvement in four organ systems: the eye, skeletal, central nervous system, and vascular system. Other organs, including the liver, hair, and skin have also been reported to be involved. The aims of treatment in classical homocystinuria vary according to the age of diagnosis. If CbS deficiency is diagnosed in the newborn infant, as ideally it should be, the aim then must be to prevent the development of ocular, skeletal, intravascular thromboembolic complications and to ensure the development of normal intelligence.