DOCSLIB.ORG

Phenylalanine Metabolism in the Phenylpyruvic Condition

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phenylalanine Metabolism in the Phenylpyruvic Condition PHENYLALANINE METABOLISM IN THE PHENYLPYRUVIC CONDITION. I. DISTRIBUTION, POOL SIZE, AND TURNOVER RATE IN HUMAN PHENYLKETONURIA Hanns-Dieter Grümer, … , Hans Koblet, Carol Woodard J Clin Invest. 1961;40(9):1758-1765. https://doi.org/10.1172/JCI104399. Research Article Find the latest version: https://jci.me/104399/pdf PHENYLALANINE METABOLISM IN THE PHENYLPYRUVIC CONDITION. I. DISTRIBUTION, POOL SIZE, AND TURNOVER RATE IN HUMAN PHENYLKETONURIA * By HANNS-DIETER GRUMER, HANS KOBLET AND CAROL WOODARD (From the Biochemical Laboratory, Pineland Hospital and Training Center, Pownal, Maine; and the Arthur G. Rotch Research Laboratories, The Boston Dispensary, Boston, Mass.) (Submitted for publication March 25, 1960; accepted May 19, 1961) The inborn metabolic error in phenylpyruvic demonstrate a defined metabolic variation from oligophrenia consists of the inability to hydroxy- the norm, they also provide the opportunity to late phenylalanine to tryrosine in any significant obtain further information that is not readily avail- amount. Recent work has focused mainly on the able in normal subjects. For example, pool size investigation of this hydroxylating system, its determinations of amino acids have rarely been purification and mode of action (1-5), the inhibi- performed and have mostly proved to be unsatis- tory effect of phenylalanine and its derivatives on factory, bceause they are based on experiments enzymes (6-9), and the prevention of mental re- with N'5-labeled amino acids and many assump- tardation by a diet low in phenylalanine (10, 11). tions have to be made [see Wu, Sendroy and With this diet the free phenylalanine of plasma Bishop (14, 15) and Tschudy and co-workers and total body fluid can be adjusted to any value (16)]. Experiments similar to ours with S35_ that might be required to study the effect of labeled methionine in lnonphenylketonuric individ- phenylalanine concentration on metabolic proc- uals have been published by Maurer (17). To esses in vivo. Bickis, Kennedy and Quastel (12), our knowledge no studies on human beings have for example, demonstrated that phenylalanine, at been made, so far, with C14-labeled amino acids, concentrations similar to those observed in the except by Gutman and co-workers (18), who esti- blood of phenylketonuric patients, inhibited the mated the pool size of glycine. The method used enzymatic degradation of tyrosine in vitro. We, by them, however, was entirely different from ours. on the other hand (13), were unable to find inhi- The use of C14-labeled amino acids eliminates bition of the breakdown of orally administered the necessity of assuming, as did Sprinson, Ritten- p-hydroxyphenylpyruvic acid in patients with berg and San Pietro (19, 20), that the rate of plasma concentrations of phenylalanine as high nitrogen transfer is faster than other metabolic as 50 mg per 100 ml. This discrepancy could be processes involved here. It will be shown later explained, for instance, by a diminished rate of that we have to make a similar assumption; p-hydroxyphenylpyruvic acid formation from tyro- namely, that equilibration of the labeled phenyl- sine in the in vitro experiments, or by a lower alanine within the body is faster than other proc- intracellular phenylalanine concentration in our esses. If it be assumed that the conversion of in vivo study than one would have expected from phenylalanine to tyrosine is negligible in the the plasma phenylalanine levels. Since the dis- penylketonuric patient, then phenylalanine can tribution coefficient of phenylalanine between tis- only be stored, incorporated into proteins, ex- sue and plasma has not yet been determined in creted as such or as its metabolites-phenylpyruvic vivo, the intracellular phenylalanine concentra- acid and phenylacetic acid. tions in our experiments were not known. In That this assumption is correct will be shown order to evaluate properly the significance of inl a second paper (21). In addition, no apprecia- metabolic experiments with phenylalanine, some ble amount of phenylpyruvic acid or phenylacetic estimate must be made of the distribution of the acid has been found in the circulating plasma of phenylalanine between plasma and tissue. phenylpyruvic patients in comparison with the Since patients with phenylpyruvic oligophrenia total amount of free phenylalanine (22). There- * This work was supported by Research Grants 2729 fore, the pool size, the turnover time, and the and 3961 from the National Institute of Mental Health. absolute turnover rate of free phenylalanine pool 1758 PHENYLALANINE METABOLISM IN THE PHENYLPYRUVIC CONDITION 1759 can be estimated by means of C14-labeled phenyl- heparinized blood samples were centrifuged at 700 RCF alanine without isolating free phenylalanine from for 10 minutes. In order to determine the radioactivity of the free L-phenylalanine in deproteinized plasma, 1.0 the plasma. The absolute turnover rate in the ml of plasma was added to 2.0 ml of 10 g per 100 ml of phenylketonuric organism is, therefore, only the an aqueous solution of trichloroacetic acid (TCA). sum of incorporation into proteins, excretion, and The resulting precipitate was centrifuged at 1,400 RCF conversion to compounds other than tyrosine. for 20 minutes and a duplicate 1.0 ml of the supernatant However, a small, nonspecific conversion to tyro- was plated on plastic planchets, 7.1 cm' in area, and dried at room temperature for counting. The samples were sine might be included. In respect to many counted in a gas-flow end-window counter with a Micro- metabolic functions, phenylketonuric patients seem mil window and an efficiency of about 22 per cent. All to behave like normal individuals; but from a values were corrected for background and self-absorption metabolic point of view they may be considered and given in counts per minute for 1.0 ml of plasma. human mutants. Thus, it might be possible to The latter values were plotted on semilogarithmic paper against time, and the resulting first straight line carry out studies at normal phenylalanine levels, was extrapolated to zero time (to). This zero time taking advantage of the existence of the metabolic value was used to calculate the distribution volume by block, to derive data applicable to persons other the formula: than phenylketonurics. cpm injected cpm per 1.0 ml protein-free plasma at to [1] MATERIALS AND METHODS The pool size of the free phenylalanine is the product of the distribution volume and the free phenylalanine plasma Two male and two female patients suffering from concentration in milliliters. phenylpyruvic oligophrenia were studied. Three (J.I., The slope of the first straight line, so obtained, per- N.C. and K.H.) had been on a diet low in phenylalanine mitted the estimation of the half-life time and the turn- for at least 3 weeks prior to the experiments. High over time of the pool. The turnover time, as used here, protein foods were replaced by a casein hydrolysate from is the reciprocal of the slope constant. The absolute turn- which phenylalanine had been removed (Lofenalac, Mead over rate is given by the quotient of milligrams of free Johnson Co.). The plasma phenylalanine was adjusted phenylalanine pool to turnover time in minutes. The to levels of 2.3 mg in J.I., 7.0 mg in N.C., and 10.5 and average concentration in 1.0 ml extravascular antipyrine 17.0 mg per 100 ml in K.H., and K.H., (the experiments space was derived from the following equation by Dost in K.H. were carried out on two different occasions). No phenylpyruvic acid was excreted in the urine as (24): amount injected - aplasma X checked by the ferric chloride test. Patient R.S. was Vplasma [2] maintained on a normal diet, excreted large amounts of Vantip. - Vplasma phenylpyruvic acid, and had a plasma phenylalanine con- where atis8ue = average apparent phenylalanine concentra- centration of 47 mg per 100 ml plasma. The experiments tion in cpm X ml-' extravascular antipyrine space at to; were carried out on 3 consecutive days, in the morning. aplasma = apparent phenylalanine level in cpm X ml-1 Breakfast was omitted. plasma at to; Vplasma = Evans blue space in ml; V..tip. First day. Determination of antipyrine space was done = antipyrine space in ml; and the distribution quotient according to Brodie, Axelrod, Soberman and Levy (23). is given by: Second day. A needle with a three-way stopcock was atissue [3] inserted into the cubital vein and a blood sample was aplasma taken for the determination of the free phenylalanine Third day. Plasma volume determinations were carried plasma level, total plasma proteins, hematocrit, and hemo- out by injecting 5.0 ml of 0.5 per cent aqueous solution globin. About 8 X 106 cpm to 11 X 106 cpm of uniformly of Evans blue (Warner-Chilcott). labeled T,-phenylalanine-C141 (specific activity 3.2 X 10' Blood samples were taken at 10, 20, and 30 minutcs, cpmi per mg), dissolved in 30 ml of physiological saline, as well as before injecting the dye. The heparinized was injected through the needle and the syringe was blood was centrifuged at 700 RCF and the clear, non- washed three times with about 10 ml of saline from an hemolyzed supernatant was measured at 600 m/i in the attached infusion bottle. A constant saline infusion was Beckman DU spectrophotometer. The resulting optical started for 5 to 6 hours (the duration of the experi- densities were plotted on linear graph paper and extrap- ments), the total amounting to not more than 350 ml. olated to zero time. From the value so obtained the Heparinized blood samples were taken at short inter- dilution of the dye was calculated. vals for 5.5 hours; in Patient K.H., for 48 hours. The In Patient N.C. the plasma volume was estimated to 1 Nuclear Chicago. This corporation claims that their be 1/22 of the body weight.
Load more

Recommended publications
  • Formation of Phenylacetic Acid and Benzaldehyde by Degradation Of
    Food Chemistry: X 2 (2019) 100037 Contents lists available at ScienceDirect Food Chemistry: X journal homepage: www.journals.elsevier.com/food-chemistry-x Formation of phenylacetic acid and benzaldehyde by degradation of phenylalanine in the presence of lipid hydroperoxides: New routes in the amino acid degradation pathways initiated by lipid oxidation products ⁎ Francisco J. Hidalgo, Rosario Zamora Instituto de la Grasa, Consejo Superior de Investigaciones Científicas, Carretera de Utrera km 1, Campus Universitario – Edificio 46, 41013 Seville, Spain ARTICLE INFO ABSTRACT Chemical compounds studied in this article: Lipid oxidation is a main source of reactive carbonyls, and these compounds have been shown both to degrade Benzaldehyde (PubChem ID: 240) amino acids by carbonyl-amine reactions and to produce important food flavors. However, reactive carbonyls 4-Oxo-2-nonenal (PubChem ID: 6445537) are not the only products of the lipid oxidation pathway. Lipid oxidation also produces free radicals. 13-Hydroperoxy-9Z,11E-octadecadienoic acid Nevertheless, the contribution of these lipid radicals to the production of food flavors by degradation of amino (PubChem ID: 5280720) acid derivatives is mostly unknown. In an attempt to investigate new routes of flavor formation, this study Phenylacetaldehyde (PubChem ID: 998) describes the degradation of phenylalanine, phenylpyruvic acid, phenylacetaldehyde, and β-phenylethylamine Phenylacetic acid (PubChem ID: 999) β-Phenylethylamine (PubChem ID: 1001) in the presence of the 13-hydroperoxide of linoleic acid, 4-oxononenal (a reactive carbonyl derived from this Phenylalanine (PubChem ID: 6140) hydroperoxide), and the mixture of both of them. The obtained results show the formation of phenylacetic acid Phenylpyruvic acid (PubChem ID: 997) and benzaldehyde in these reactions as a consequence of the combined action of carbonyl-amine and free radical reactions for amino acid degradation.
    [Show full text]
  • Biochemical Screening and PTEN Mutation Analysis in Individuals with Autism Spectrum Disorders and Macrocephaly
    European Journal of Human Genetics (2014) 22, 273–276 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg SHORT REPORT Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly Judith A Hobert1, Rebecca Embacher2, Jessica L Mester1,3, Thomas W Frazier II1,2 and Charis Eng*,1,3,4,5 Unlike some other childhood neurodevelopmental disorders, no diagnostic biochemical marker has been identified in all individuals with an autism spectrum disorder (ASD). This deficit likely results from genetic heterogeneity among the population. Therefore, we evaluated a subset of individuals with ASDs, specifically, individuals with or without macrocephaly in the presence or absence of PTEN mutations. We sought to determine if amino or organic acid markers could be used to identify individuals with ASDs with or without macrocephaly in the presence or absence of PTEN mutations, and to establish the degree of macrocephaly in individuals with ASDs and PTEN mutation. Urine, blood and occipital–frontal circumference (OFC) measurements were collected from 69 individuals meeting DSM-IV-TR criteria. Urine and plasma samples were subjected to amino and organic acid analyses. PTEN was Sanger-sequenced from germline genomic DNA. Germline PTEN mutations were identified in 27% (6/22) of the macrocephalic ASD population. All six PTEN mutation-positive individuals were macrocephalic with average OFC þ 4.35 standard deviations (SDs) above the mean. No common biochemical abnormalities were identified in macrocephalic ASD individuals with or without PTEN mutations. In contrast, among the collective ASD population, elevation of urine aspartic acid (87%; 54/62), plasma taurine (69%; 46/67) and reduction of plasma cystine (72%; 46/64) were observed.
    [Show full text]
  • Retropath2.0: a Retrosynthesis Workflow for Metabolic Engineers
    bioRxiv preprint doi: https://doi.org/10.1101/141721; this version posted June 29, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. RetroPath2.0: a retrosynthesis workflow for metabolic engineers Baudoin Delépine1,2,3,§, Thomas Duigou3,§, Pablo Carbonell4, Jean-Loup Faulon3,1,2,4,* 1 CNRS-UMR8030 / Laboratoire iSSB, Université Paris-Saclay, Évry 91000, France 2 CEA, DRF, IG, Genoscope, Évry 91000, France 3 Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France 4 SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK §: These authors contributed equally to this work. *: Corresponding author at: Micalis, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78352 JOUY-EN-JOSAS, FRANCE; E-mail address: [email protected] Highlights • State-of-the-art Computer-Aided Design retrosynthesis solutions lack open source and ease of use • We propose RetroPath2.0 a modular and open-source workflow to perform retrosynthesis • RetroPath2.0 computes reaction network between Source and Sink sets of compounds • RetroPath2.0 is distributed as a KNIME workflow for desktop computers • RetroPath2.0 is ready-for-use and distributed with reaction rules Funding This work was supported by the French National Research Agency [ANR-15-CE1-0008], the Biotechnology and Biological Sciences Research Council, Centre for synthetic biology of fine and speciality chemicals [BB/M017702/1]; Synthetic Biology Applications for Protective Materials [EP/N025504/1], and GIP Genopole.
    [Show full text]
  • Engineering an Alcohol Dehydrogenase for Balancing
    Research Article Cite This: ACS Sustainable Chem. Eng. 2019, 7, 15706−15714 pubs.acs.org/journal/ascecg Engineering an Alcohol Dehydrogenase for Balancing Kinetics in NADPH Regeneration with 1,4-Butanediol as a Cosubstrate † # † # ‡ § † † † Guochao Xu, , Cheng Zhu, , Aitao Li, Yan Ni, Ruizhi Han, Jieyu Zhou, and Ye Ni*, † Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu, China ‡ Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Wuhan 430062, China § Department of Biomedical Engineering, Eindhoven University of Technology, NL-5600 Eindhoven, MB, Netherlands *S Supporting Information ABSTRACT: Cofactor regeneration using diols as “smart cosubstrates” is one of the most promising approaches, due to the thermodynamic preference and 0.5-equiv requirement. In order to establish an efficient NADPH regeneration system with 1,4-butanediol (1,4-BD), a NADP+- dependent alcohol dehydrogenase from Kluyveromyces polysporus (KpADH) was engineered to solve the kinetic imbalance. Several hotspots were identified through molecular dynamic simulation and subjected to saturation and combinatorial mutagenesis. Variant KpADHV84I/Y127M −1 exhibited a lower KM of 15.1 mM and a higher kcat of 30.1 min than WTKpADH. The oxidation of 1,4-BD to 4-hydroxybutanal was found to be the rate-limiting step, for which the kcat/KM value of double mutant −1· −1 KpADHV84I/Y127M was 2.00 min mM , 11.6-fold higher than that of WT KpADH. KpADHV84I/Y127M preferred diols with a longer chain length − (C5 C6). The ratio of kcat/KM toward 2-hydroxytetrahydrofuran (2-HTHF), in comparison to 1,4-BD, in KpADHV84I/Y127M was dramatically reduced by almost 100-fold compared to WTKpADH, which was advantageous for NADPH regeneration.
    [Show full text]
  • Publishers Version
    Engineering an alcohol dehydrogenase for nalancing kinetics in NADPH regeneration with 1,4-butanediol as a cosubstrate Citation for published version (APA): Xu, G., Zhu, C., Li, A., Ni, Y., Han, R., Zhou, J., & Ni, Y. (2019). Engineering an alcohol dehydrogenase for nalancing kinetics in NADPH regeneration with 1,4-butanediol as a cosubstrate. ACS Sustainable Chemistry and Engineering, 7(18), 15706-15714. https://doi.org/10.1021/acssuschemeng.9b03879 Document license: TAVERNE DOI: 10.1021/acssuschemeng.9b03879 Document status and date: Published: 16/09/2019 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.
    [Show full text]
  • Ralfuranone Biosynthesis in Ralstonia Solanacearum Suggests Functional Divergence in the Quinone Synthetase Family of Enzymes
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Chemistry & Biology Article Ralfuranone Biosynthesis in Ralstonia solanacearum Suggests Functional Divergence in the Quinone Synthetase Family of Enzymes Barbara Wackler,1 Patrick Schneider,1 Jonathan M. Jacobs,2 Julia Pauly,1 Caitilyn Allen,2 Markus Nett,3 and Dirk Hoffmeister1,* 1Department Pharmaceutical Biology at the Hans-Kno¨ ll-Institute, Friedrich-Schiller-Universita¨ t Jena, Beutenbergstrasse 11a, 07745 Jena, Germany 2Department of Plant Pathology, University of Wisconsin-Madison, 1630 Linden Drive, Madison, WI 53706, USA 3Leibniz Institute for Natural Product Research and Infection Biology—Hans-Kno¨ ll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany *Correspondence: [email protected] DOI 10.1016/j.chembiol.2011.01.010 SUMMARY VsrAD and PhcA, and secondary metabolism has been demon- strated and led to the identification of a new small molecule, Ralstonia solanacearum is a destructive crop plant ralfuranone (4-phenylfuran-2(5H)-one, 1, Figure 1)(Schneider pathogen and produces ralfuranone, i.e., a mono- et al., 2009). Although achiral and little functionalized, this bicy- phenyl-substituted furanone. Extensive feeding clic secondary product attracted our attention as the origin of experiments with 13C-labeled L-phenylalanine now the carbon atoms was elusive. Initially, we hypothesized that proved that all carbon atoms of the heterocycle the aromatic system may be derived from L-phenylalanine, and derive, after deamination, from this aromatic amino that transfer of malonyl-CoA to the former may provide the carbon atoms to complete furanone synthesis. Chemical char- acid. A genetic locus was identified which encodes acterization of a new, yet related natural product, ralfuranone B the aminotransferase RalD and the furanone synthe- (2, Figure 1), prompted us to propose a revised biosynthetic tase RalA.
    [Show full text]
  • Ep 1 602 354 B1
    (19) & (11) EP 1 602 354 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 8/88 (2006.01) A61Q 5/00 (2006.01) 05.11.2008 Bulletin 2008/45 (86) International application number: (21) Application number: 04716754.9 PCT/JP2004/002606 (22) Date of filing: 03.03.2004 (87) International publication number: WO 2004/080433 (23.09.2004 Gazette 2004/39) (54) Use of polyglutamic acid or its salts Verwendung von Polyglutamatsäure oder deren Salze Utilisation de l’acide polyglutamique ou ses sels. (84) Designated Contracting States: • YAMADA, Kikumi, AT BE BG CH CY CZ DE DK EE ES FI FR GB GR c/o Ichimaru Pharcos Co., Ltd. HU IE IT LI LU MC NL PL PT RO SE SI SK TR Motosu-shi, Gifu 501-0475 (JP) (30) Priority: 10.03.2003 JP 2003062688 (74) Representative: Gille Hrabal Struck Neidlein Prop Roos (43) Date of publication of application: Patentanwälte 07.12.2005 Bulletin 2005/49 Brucknerstrasse 20 40593 Düsseldorf (DE) (73) Proprietor: Meiji Seika Kaisha Ltd. Chuo-ku, (56) References cited: Tokyo 104-8002 (JP) EP-A- 0 774 247 WO-A1-20/04039339 JP-A- 1 146 986 JP-A- 8 291 036 (72) Inventors: JP-A- 10 298 037 JP-A- 10 298 042 • HASEBE, Kohei, JP-A- 11 240 827 JP-A- 59 209 635 c/o Ichimaru Pharcos Co., Ltd. JP-A- 2001 354 542 JP-A- 2002 145 723 Motosu-shi, Gifu 501-0475 (JP) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • The Pennsylvania State University the Graduate School College Of
    The Pennsylvania State University The Graduate School College of Engineering PRODUCTION OF PHENYLPYRUVIC ACID AND PHYTASE BY MICROBIAL FERMENTATION A Dissertation in Agricultural and Biological Engineering by Hasan Bugra Coban @2014 Hasan Bugra Coban Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2014 The dissertation of Hasan Bugra Coban was reviewed and approved* by the following. Ali Demirci Professor of Agricultural and Biological Engineering Dissertation Advisor Chair of Committee Virenda Puri Distinguished Professor of Agricultural and Biological Engineering Paul H. Patterson Professor of Animal Science Ryan J. Elias Associate Professor of Food Science Paul Heinemann Professor of Agricultural and Biological Engineering Head of the Department of Agricultural and Biological Engineering *Signatures are on file in the Graduate School ABSTRACT Feed and food additives are very popular in industry to increase the quality of diets. They have been used for various applications such as nutritional quality enhancing, coloring, flavor enhancing, antimicrobial effects, thickening, stabilization, increasing shelf-life, and calorie reducing. Phenylpyruvic acid (PPA) and phytase are just two of the important feed and food additives. PPA and phytase have important applications in the industry. PPA is being experimentally used as a substitute for phenylalanine in feeds to decrease excessive nitrogen accumulation in the manure to prevent negative effects on the environment. PPA is also used for kidney patient’s diets to decrease urea accumulation in the body. Additionally, PPA is a very important compound for cheese and wine production to generate a specific taste and aroma. Phytase breaks down phytate, which serves as an anti-nutrient agent by binding divalent ions, amino acids, and proteins in the intestine.
    [Show full text]
  • Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19
    medRxiv preprint doi: https://doi.org/10.1101/2020.04.05.20053819; this version posted April 26, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19 Di Wu1,2,#, Ting Shu3,4,2,#, Xiaobo Yang5,#, Jian-Xin Song6,#, Mingliang Zhang7,#, Chengye Yao8,#, Wen Liu3,4, Muhan Huang1,2, Yuan Yu5, Qingyu Yang3,4,2, Tingju Zhu3,4, Jiqian Xu5, Jingfang Mu1,2, Yaxin Wang5, Hong Wang7, Tang Tang7, Yujie Ren1,2, Yongran Wu5, Shu-Hai Lin9*, Yang Qiu 1,2,3,10*, Ding-Yu Zhang3,4*, You Shang5,3,4*, Xi Zhou1,2,3,10* 1 Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology & Wuhan Jinyintan Hospital, Wuhan Institute of Virology, Center for Biosafety Mega- Science, Chinese Academy of Sciences (CAS), Wuhan, Hubei 430023 China 2 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, CAS, Wuhan, Hubei 430071, China 3 Center for Translational Medicine, Jinyintan Hospital, Wuhan, Hubei 430023 China 4 Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology & Wuhan Jinyintan Hospital, Wuhan Jinyintan Hospital, Wuhan, Hubei 430023 China 5 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 China 6 Department of Infectious Diseases, Tongji
    [Show full text]
  • Pattern Recognition Methods for the Prediction of Chemical Structures of Fungal Secondary Metabolites
    !"##$%&'%$()*&+#+)&',$#-)./'0)%'#-$'1%$.+(#+)&')0' (-$,+("2'/#%3(#3%$/')0'03&*"2'/$()&."%4',$#"5)2+#$/' ! ! ! !"##$%&'&"()! ! "#!$%&'(&&! )*+!,+-%(.+/+0)1!'#.!)*+!2+3.++!#'! !*+(,&(%-%$%./-)'&.%'0"./1-2!%3-%$%3-)'&34! - - - - ! 5.6/"&&$+-&(-&7$-8(.),"0-(9-&7$-:',.0&;-(9- <"(0(=",'0-5,"$),$#! (9-&7$-:%"$+%",7-5,7"00$%->)"?$%#"&;-@$)'! - - - !"!5'='%-87')=+$?-A(%$#$%&'()*#+,#-./)0.)1# # !+*0!+0!BC!"[email protected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
    [Show full text]
  • Production of the Flavor Compound Benzaldehyde by Lactic Acid Bacteria: Role of Manganese and Itstranspor T Systems Inlactobacillus Plantarum
    Production of the Flavor Compound Benzaldehyde by Lactic Acid Bacteria: Role of Manganese and itsTranspor t Systems inLactobacillus plantarum Masja Nierop Groot CENTRALE LANOBOUWCATALOGUS 0000 0873 7500 Promotor: Prof.dr .W.M .d eVo s Hoogleraar ind e Microbiologie, Themadirecteur bij hetWageninge n Centre for Food Sciences Co-promotor: Dr. M.Kleerebeze m Projectleider bij hetWageninge n Centre for Food Sciences Promotiecommissie: Prof.dr . M. Muller Wageningen Universiteit Prof.dr . J. Delcour University of Louvain-la-Neuve, Belgium Prof.dr . K. Hellingwerf Universiteit van Amsterdam Dr.J .Sikkem a Friesland Coberco Dairy Foods .r,Ci^ Production of the Flavor Compound Benzaldehyde by Lactic Acid Bacteria: Role of Manganese and itsTranspor t Systems inLactobacillus plantarum Masja Nathalie Nierop Groot Proefschrift terverkrijgin g vand egraa d van doctor opgeza g van de rector magnificusva n Wageningen Universiteit, prof.dr . ir. L. Speelman, in hetopenbaa r te verdedigen opwoensda g 19decembe r 2001de s ochtends omel f uur ind eAula . 2>r.£j> Nierop Groot, M.N. Production ofth e Flavor Compound Benzaldehyde by Lactic Acid Bacteria: Roleo f Manganese and itsTranspor t Systems inLactobacillus plantarum ThesisWageninge n University, 2001. Met Nederlandse samenvatting ISBN: 90-5808-539-2 Stellingen 1. Het is onwaarschijnlijk dat de lage intracellulaire mangaan concentratie in de door Hao et al. (1999) geconstrueerde Lactobacillusplantarum mutant het gevolg is van uitschakeling van het mntAge nalleen . Hao, Z., H.R. Reiske and D.B. Wilson. 1999. Characterization of cadmium uptake in Lactobacillus plantarum and isolation of cadmium and manganese uptake mutants. Applied and Environmental Microbiology 65: 4741-4745. Dit proefschrift 2.
    [Show full text]
  • Thesis Title
    Elucidation of selected Maillard reaction pathways in alanine and phenylalanine model systems through isotope labelling and pyrolysis-GC/MS based techniques FONG LAM CHU Department of Food Science and Agricultural Chemistry McGill University, Montreal August 2009 Thesis submitted to the Faculty of Graduate and Post-Doctoral studies in partial fulfillment of the requirement of the degree of Doctor in Philosophy © Fong Lam Chu, 2009 Library and Archives Bibliothèque et Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l’édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN:978-0-494-61905-6 Our file Notre référence ISBN: 978-0-494-61905-6 NOTICE: AVIS: The author has granted a non- L’auteur a accordé une licence non exclusive exclusive license allowing Library and permettant à la Bibliothèque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l’Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans le loan, distribute and sell theses monde, à des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L’auteur conserve la propriété du droit d’auteur ownership and moral rights in this et des droits moraux qui protège cette thèse. Ni thesis. Neither the thesis nor la thèse ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent être imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation.
    [Show full text]