The Clinical Significance of the Organic Acids Test
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Cloning, Biochemical Characterization and Inhibition of Alanine Racemase from Streptococcus Iniae
bioRxiv preprint doi: https://doi.org/10.1101/611251; this version posted April 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Cloning, Biochemical Characterization and Inhibition of Alanine racemase from Streptococcus iniae Murtala Muhammad, Yangyang Li, Siyu Gong, Yanmin Shi, Jiansong Ju, Baohua Zhao*, Dong Liu* College of Life Science, Hebei Normal University, Shijiazhuang 050024, China; *Correspondence: Baohua Zhao and Dong Liu; E-mail: [email protected], [email protected]; College of Life Science, Hebei Normal University, Shijiazhuang 050024, China. Running Title: Inhibitors of alanine racemase Summary statement: Antimicrobial target 1 bioRxiv preprint doi: https://doi.org/10.1101/611251; this version posted April 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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 Streptococcus iniae is a pathogenic and zoonotic bacteria that impacted high mortality to many fish species, as well as capable of causing serious disease to humans. Alanine racemase (Alr, EC 5.1.1.1) is a pyridoxal-5′-phosphate (PLP)-containing homodimeric enzyme that catalyzes the racemization of L-alanine and D-alanine. In this study, we purified alanine racemase from the pathogenic strain of S. iniae, determined its biochemical characteristics and inhibitors. The alr gene has an open reading frame (ORF) of 1107 bp, encoding a protein of 369 amino acids, which has a molecular mass of 40 kDa. The optimal enzyme activity occurred at 35°C and a pH of 9.5. -
WINE CHEM 101 Part B by Bob Peak
WINE CHEM 101 Part B By Bob Peak In last year’s catalog and newsletter, we began a discussion of the chemistry of wine and winemaking— Wine Chem 101, Part A—with details about conversion of sugars to alcohol. (That article is still available at thebeveragepeople. com). At the end of the article, I credited wine acids for the “zing” in wine flavor that lifts it above ordinary bever-ages. So, in this issue, I will tackle that part of Wine Chem: Acid. The two major organic acid components of grapes and grape juice are tartaric and malic acids, usually starting at about a 50-50 ratio. Together, they create the low pH conditions that help make wine a stable beverage and provide the pleasant tartness we all associate with it. The combined range of these acids in fresh grape juice will usually fall between 3 and 15 grams per liter (or 0.3 to 1.5%). Although this wide range of acid levels—measured as TA or Titratable Acidity—can be seen around the world, most North Coast grape juice comes in between 0.4 and 0.7% TA, with about 0.65% preferred. There is also a trace of citric acid in grapes, but it is not a significant contributor to TA. Together, these acids are the “fixed” acids of grape juice, joined in some wines by lactic acid from malolactic fermentation. The term “fixed” is used to distinguish from the spoilage acids of wine, the volatile acids. Those acids—mostly acetic acid—are the products of vinegar fermenta-tion and will introduce unpleasant aromas to wine at very low levels. -
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. -
Orfadin, INN-Nitisinone
SCIENTIFIC DISCUSSION 1. Introduction 1.1 Problem statement Hereditary tyrosinaemia type 1 (HT-1) is a devastating inherited disease, mainly of childhood. It is characterised by severe liver dysfunction, impaired coagulation, painful neurological crises, renal tubular dysfunction and a considerable risk of hepatocellular carcinoma (Weinberg et al. 1976, Halvorsen 1990, Kvittingen 1991, van Spronsen et al. 1994, Mitchell et al. 1995). The condition is caused by an inborn error in the final step of the tyrosine degradation pathway (Lindblad et al. 1977). The incidence of HT-1 in Europe and North America is about one in 100,000 births, although in certain areas the incidence is considerably higher. In the province of Quebec, Canada, it is about one in 20,000 births (Mitchell et al. 1995). The mode of inheritance is autosomal recessive. The primary enzymatic defect in HT-1 is a reduced activity of fumarylacetoacetate hydrolase (FAH) in the liver, the last enzyme in the tyrosine degradation pathway. As a consequence, fumaylacetoacetate (FAA) and maleylacetoacetate (MAA), upstream of the enzymatic block, accumulate. Both intermediates are highly reactive and unstable and cannot be detected in the serum or urine of affected children. Degradation products of MAA and FAA are succinylacetone (SA) and succinylacetoacetate (SAA) which are (especially SA) toxic, and which are measurable in the serum and urine and are hallmarks of the disease. SA is also an inhibitor of Porphobilinogen synthase (PBG), leading to an accumulation of 5-aminolevulinate (5-ALA) which is thought to be responsible for the neurologic crises resembling the crises of the porphyrias. The accumulation of toxic metabolites starts at birth and the severity of phenotype is reflected in the age of onset of symptoms (Halvorsen 1990, van Spronsen et al. -
Acetaldehyde Stimulation of Net Gluconeogenic Carbon Movement from Applied Malic Acid in Tomato Fruit Pericarp Tissue'12
Plant Physiol. (1991) 95, 954-960 Received for publication July 18, 1990 0032-0889/91 /95/0954/07/$01 .00/0 Accepted November 16, 1990 Acetaldehyde Stimulation of Net Gluconeogenic Carbon Movement from Applied Malic Acid in Tomato Fruit Pericarp Tissue'12 Anna Halinska3 and Chaim Frenkel* Department of Horticulture, Rutgers-The State University, New Brunswick, New Jersey 08903 ABSTRACT appears to stimulate a respiratory upsurge in climacteric and Applied acetaldehyde is known to lead to sugar accumulation nonclimacteric fruit including blueberry and strawberry (13) in fruit including tomatoes (Lycopersicon esculentum) (O Paz, HW as well as in potato tubers (24) and an enhanced metabolite Janes, BA Prevost, C Frenkel [1982] J Food Sci 47: 270-274) turnover in ripening fig (9). The action of AA may be inde- presumably due to stimulation of gluconeogenesis. This conjec- pendent of ethylene, because AA was shown on one hand to ture was examined using tomato fruit pencarp discs as a test inhibit ethylene biosynthesis (E Pesis, personal communica- system and applied -[U-14C]malic acid as the source for gluco- tion) and on the other to promote softening and degreening neogenic carbon mobilization. The label from malate was re- in pear even when ethylene biosynthesis and action were covered in respiratory C02, in other organic acids, in ethanol arrested ( 14). insoluble material, and an appreciable amount in the ethanol The finding that AA application is accompanied by an soluble sugar fraction. In Rutgers tomatoes, the label recovery in increase in the total sugars content in tomato (19, 21) raises the sugar fraction and an attendant label reduction in the organic acids fraction intensified with fruit ripening. -
Selection and Characterization of Alanine Racemase Inhibitors Against
Wang et al. BMC Microbiology (2017) 17:122 DOI 10.1186/s12866-017-1010-x RESEARCHARTICLE Open Access Selection and characterization of alanine racemase inhibitors against Aeromonas hydrophila Yaping Wang1, Chao Yang2, Wen Xue1, Ting Zhang1, Xipei Liu1, Jiansong Ju1, Baohua Zhao1* and Dong Liu1* Abstract Background: Combining experimental and computational screening methods has been of keen interest in drug discovery. In the present study, we developed an efficient screening method that has been used to screen 2100 small-molecule compounds for alanine racemase Alr-2 inhibitors. Results: We identified ten novel non-substrate Alr-2 inhibitors, of which patulin, homogentisic acid, and hydroquinone were active against Aeromonas hydrophila. The compounds were found to be capable of inhibiting Alr-2 to different extents with 50% inhibitory concentrations (IC50) ranging from 6.6 to 17.7 μM. These compounds inhibited the growth of A. hydrophila with minimal inhibitory concentrations (MICs) ranging from 20 to 120 μg/ml. These compounds have no activity on horseradish peroxidase and D-amino acid oxidase at a concentration of 50 μM. The MTT assay revealed that homogentisic acid and hydroquinone have minimal cytotoxicity against mammalian cells. The kinetic studies indicated a competitive inhibition of homogentisic acid against Alr-2 with an inhibition constant (Ki) of 51.7 μM, while hydroquinone was a noncompetitive inhibitor with a Ki of 212 μM. Molecular docking studies suggested that homogentisic acid binds to the active site of racemase, while hydroquinone lies near the active center of alanine racemase. Conclusions: Our findings suggested that combining experimental and computational methods could be used for an efficient, large-scale screening of alanine racemase inhibitors against A. -
3-Aroyl Pyroglutamic Acid Amides †
Proceeding Paper Synthesis of (2S,3S)-3-Aroyl Pyroglutamic Acid Amides † Lucia Pincekova * and Dusan Berkes * Department of Organic Chemistry, Slovak Technical University, Radlinského 9, SK-812 37 Bratislava, Slovakia * Correspondence: [email protected] (L.P.); [email protected] (D.B.) † Presented at the 24th International Electronic Conference on Synthetic Organic Chemistry, 15 November–15 December 2020; Available online: https://ecsoc-24.sciforum.net/. Abstract: A new methodology for the asymmetric synthesis of enantiomerically enriched 3-aroyl pyroglutamic acid derivatives has been developed through effective 5-exo-tet cyclization of N-chlo- roacetyl aroylalanines. The three-step sequence starts with the synthesis of N-substituted (S,S)-2- amino-4-aryl-4-oxobutanoic acids via highly diastereoselective tandem aza-Michael addition and crystallization-induced diastereomer transformation (CIDT). Their N-chloroacetylation followed by base-catalyzed cyclization and ultimate acid-catalyzed removal of chiral auxiliary without loss of stereochemical integrity furnishes the target substituted pyroglutamic acids. Finally, several series of their benzyl amides were prepared as 3-aroyl analogs of known P2X7 antagonists. Keywords: pyroglutamic acid; P2X7 receptors; aza-Michael addition; CIDT; N-debenzylation 1. Introduction Pyroglutamic acid and its derivatives are a valuable class of compounds found in various natural products and pharmaceuticals, representing either an important chiral Citation: Pincekova, L.; Berkes, D. auxiliary or building block for the asymmetric synthesis of many biologically and phar- Synthesis of (2S,3S)-3-Aroyl maceutically valuable compounds [1]. Moreover, pyroglutamic acid derivatives have re- Pyroglutamic Acid Amides. Chem. cently appeared to be efficient antagonists of specific types of purinergic receptors. Their Proc. -
Seeding the Pregenetic Earth: Meteoritic Abundances Of
Accepted for publication in ApJ A Preprint typeset using LTEX style emulateapj v. 5/2/11 SEEDING THE PREGENETIC EARTH: METEORITIC ABUNDANCES OF NUCLEOBASES AND POTENTIAL REACTION PATHWAYS Ben K. D. Pearce1,4 and Ralph E. Pudritz2,3,5 Accepted for publication in ApJ ABSTRACT Carbonaceous chondrites are a class of meteorite known for having a high content of water and organics. In this study, abundances of the nucleobases, i.e., the building blocks of RNA and DNA, found in carbonaceous chondrites are collated from a variety of published data and compared across various meteorite classes. An extensive review of abiotic chemical reactions producing nucleobases is then performed. These reactions are then reduced to a list of 15 individual reaction pathways that could potentially occur within meteorite parent bodies. The nucleobases guanine, adenine and uracil are found in carbonaceous chondrites in the amounts of 1–500 ppb. It is currently unknown which reaction is responsible for their synthesis within the meteorite parent bodies. One class of carbonaceous meteorites dominate the abundances of both amino acids and nucleobases—the so-called CM2 (e.g. Murchison meteorite). CR2 meteorites (e.g. Graves Nunataks) also dominate the abundances of amino acids, but are the least abundant in nucleobases. The abundances of total nucleobases in these two classes are 330 ± 250 ppb and 16 ± 13 ppb respectively. Guanine most often has the greatest abundances in carbonaceous chondrites with respect to the other nucleobases, but is 1–2 orders of magnitude less abundant in CM2 meteorites than glycine (the most abundant amino acid). Our survey of the reaction mechanisms for nucleobase formation suggests that Fischer-Tropsch synthesis (i.e. -
Production of Succinic Acid by E.Coli from Mixtures of Glucose
2005:230 CIV MASTER’S THESIS Production of Succinic Acid by E. coli from Mixtures of Glucose and Fructose ANDREAS LENNARTSSON MASTER OF SCIENCE PROGRAMME Chemical Engineering Luleå University of Technology Department of Chemical Engineering and Geosciences Division of Biochemical and Chemical Engineering 2005:230 CIV • ISSN: 1402 - 1617 • ISRN: LTU - EX - - 05/230 - - SE Abstract Succinic acid, derived from fermentation of renewable feedstocks, has the possibility of replacing petrochemicals as a building block chemical. Another interesting advantage with biobased succinic acid is that the production does not contribute to the accumulation of CO2 to the environment. The produced succinic acid can therefore be considered as a “green” chemical. The bacterium used in this project is a strain of Escherichia coli called AFP184 that has been metabolically engineered to produce succinic acid in large quantities from glucose during anaerobic conditions. The objective with this thesis work was to evaluate whether AFP184 can utilise fructose, both alone and in mixtures with glucose, as a carbon source for the production of succinic acid. Hydrolysis of sucrose yields a mixture of fructose and glucose in equal ratio. Sucrose is a common sugar and the hydrolysate is therefore an interesting feedstock for the production of succinic acid. Fermentations with an initial sugar concentration of 100 g/L were conducted. The sugar ratios used were 100 % fructose, 100 % glucose and a mixture with 50 % fructose and glucose, respectively. The fermentation media used was a lean, low- cost media based on corn steep liquor and a minimal addition of inorganic salts. Fermentations were performed with a 12 L bioreactor and the acid and sugar concentrations were analysed with an HPLC system. -
Response of Downy Oak (Quercus Pubescens Willd.) to Climate Change: Transcriptome Assembly, Differential Gene Analysis and Targe
plants Article Response of Downy Oak (Quercus pubescens Willd.) to Climate Change: Transcriptome Assembly, Differential Gene Analysis and Targeted Metabolomics Jean-Philippe Mevy 1,*, Beatrice Loriod 2, Xi Liu 3, Erwan Corre 3, Magali Torres 2, Michael Büttner 4, Anne Haguenauer 1, Ilja Marco Reiter 5, Catherine Fernandez 1 and Thierry Gauquelin 1 1 CNRS, Aix-Marseille University, Avignon University, IRD, IMBE, 13331 Marseille, France; [email protected] (A.H.); [email protected] (C.F.); [email protected] (T.G.) 2 TGML-TAGC—Inserm UMR1090 Aix-Marseille Université 163 avenue de Luminy, 13288 Marseille, France; [email protected] (B.L.); [email protected] (M.T.) 3 CNRS, Sorbonne Université, FR2424, ABiMS platform, Station Biologique, 29680 Roscoff, France; xi.liu@sb-roscoff.fr (X.L.); erwan.corre@sb-roscoff.fr (E.C.) 4 Metabolomics Core Technology Platform Ruprecht-Karls-University Heidelberg Centre for Organismal Studies (COS) Im Neuenheimer Feld 360, 69120 Heidelberg, Germany; [email protected] 5 Research Federation ECCOREV FR3098, CNRS, 13545 Aix-en-Provence, France; [email protected] * Correspondence: [email protected]; Tel.: +33-0413550766 Received: 20 July 2020; Accepted: 1 September 2020; Published: 4 September 2020 Abstract: Global change scenarios in the Mediterranean basin predict a precipitation reduction within the coming hundred years. Therefore, increased drought will affect forests both in terms of adaptive ecology and ecosystemic services. However, how vegetation might adapt to drought is poorly understood. In this report, four years of climate change was simulated by excluding 35% of precipitation above a downy oak forest. -
Methods, Compounds, Compositions and Vehicles for Delivering 3-Amino-1-Propanesulfonic Acid
(19) TZZ _ T (11) EP 2 862 581 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 22.04.2015 Bulletin 2015/17 A61K 47/48 (2006.01) C07K 5/06 (2006.01) C07K 5/08 (2006.01) C07C 309/15 (2006.01) (2006.01) (2006.01) (21) Application number: 14200552.9 C07D 207/16 C07D 209/20 C07D 217/24 (2006.01) C07D 233/64 (2006.01) (2006.01) (2006.01) (22) Date of filing: 12.10.2007 C07D 291/02 C07D 333/24 C12P 11/00 (2006.01) A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61P 25/28 (2006.01) (84) Designated Contracting States: (72) Inventor: The designation of the inventor has not AT BE BG CH CY CZ DE DK EE ES FI FR GB GR yet been filed HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR (74) Representative: Hoffmann Eitle Patent- und Rechtsanwälte PartmbB (30) Priority: 12.10.2006 US 851039 P Arabellastraße 30 12.04.2007 US 911459 P 81925 München (DE) (62) Document number(s) of the earlier application(s) in Remarks: accordance with Art. 76 EPC: This application was filed on 30-12-2014 as a 07875176.5 / 2 089 417 divisional application to the application mentioned under INID code 62. (71) Applicant: BHI Limited Partnership Laval, QC H7V 4A7 (CA) (54) Methods, compounds, compositions and vehicles for delivering 3- amino-1-propanesulfonic acid (57) The invention relates to methods, compounds, that will yield or generate 3APS, either in vitro or in vivo. -
COMPILATION of AMINO ACIDS, DRUGS, METABOLITES and OTHER COMPOUNDS in MASSTRAK AMINO ACID ANALYSIS SOLUTION Paula Hong, Kendon S
COMPILATION OF AMINO ACIDS, DRUGS, METABOLITES AND OTHER COMPOUNDS IN MASSTRAK AMINO ACID ANALYSIS SOLUTION Paula Hong, Kendon S. Graham, Alexandre Paccou, T homas E. Wheat and Diane M. Diehl INTRODUCTION LC conditions Physiological amino acid analysis is commonly performed to LC System: Waters ACQUITY UPLC® System with TUV monitor and study a wide variety of metabolic processes. A wide Column: MassTrak AAA Column 2.1 x 150 mm, 1.7 µm variety of drugs, foods, and metabolic intermediates that may Column Temp: 43 ˚C be present in biological fluids can appear as peaks in amino Flow Rate: 400 µL/min. acid analysis, therefore, it is important to be able to identify Mobile Phase A: MassTrak AAA Eluent A Concentrate, unknown compounds.1,2,3 The reproducibility and robustness of diluted 1:10 the MassTrak Amino Acid Analysis Solution make this method well Mobile Phase B: MassTrak AAA Eluent B suited to such a study as well.4 Weak Needle Wash: 5/95 Acetonitrile/Water Strong Needle Wash: 95/5 Acetonitrile/Water Gradient: MassTrak AAA Standard Gradient (as provided in kit) Detection: UV @ 260 nm Injection Volume: 1 µL EXPERIMENTAL Injection Mode: Partial Loop with Needle Overfill (PLNO) Compound sample preparation A library of compounds was assembled. Each compound was derivatized individually and spiked into the MassTrak™ AAA Solution Standard prior to chromatographic analysis. The elution RESULTS AND DISCUSSION position of each tested compound could be related to known amino acids. A wide variety of antibiotics, pharmaceutical compounds and metabolite by-products are found in biological fluids. The reten- 1.