DOCSLIB.ORG

Recent Developments in the Biosynthesis of the Tropane Alkaloids1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Developments in the Biosynthesis of the Tropane Alkaloids1 Review 339 Recent Developments in the Biosynthesis of the Tropane Alkaloids1 Edward Leete2 Presented in part at the 37th Annual Congress of the Gesellschaft furArzneipflanzenforschung, September 5—9, 1989, Braunschweig, FRG 2NaturalProducts Laboratory, Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, U.S.A. Received: August 28, 1989 ring system will be discussed in this article. Several signifi- Abstract cant discoveries have been made since our last review on this subject (4). Some of these advances have been recorded Recent work on the biosynthesis of the recently in accounts of the chemistry and biochemistry of tropane moiety of cocaine, hyoscamine, scopolamine, the tropane alkaloids (5—7). and related alkaloids is reviewed. Revision of the gener- ally accepted biosynthetic pathway to these alkaloids is Structural Variations in the now proposed in the light of new discoveries. New infor- Tropane Alkaloids mation on the biosynthesis of some of the acid moieties (benzoic, tiglic and tropic acid) of the tropane ester al- By definition, the bicyclic hetero cyclic com- kaloids is also discussed. pound 8-azabicyclo[3.2.1]octane (4) is present in all the tropane alkaloids. Tropane (5) is its 8-methyl derivative. Key words The six-membered piperidine ring is usually depicted in the chair form (as in 6), however in some of its reactions it Biosynthesis, tropane alkaloids, cocaine, adopts the boat conformation (as in 7). Over 150 (7) al- hyoscyamine, scopolamine, tropane ester alkaloids. kaloids are known which contain the bicyclic ring system 4. Some of these alkaloids are depicted in Fig. 3. The absolute configuration of the more common alkaloids has been eluci- dated and the chirality, using the (R), (S) symbolism, is indi- Introduction cated on the structural formulas. The numbering of the tropane nucleus in hyoscyamine will be used for all the There are currently about 10,000 alkaloidstropane alkaloids so that their biosynthetic relationship can of known structure (1). Over the last 40 years much hasbe more easily understood. According to IUPAC rules, been learned about the biosynthesis of this group of second-scopolamine should be numbered with the (R)-bridgehead ary natural products. They arise from a relatively smallcarbon as C-i (R having a higher priority than S in such a number of organic compounds which are found in almostsymmetrical molecule). The majority of the tropane al- all living systems (acetic acid, anthranilic acid, arginine, kaloids are esters of hydroxytropanes with a wide variety of lysine, mevalonic acid, nicotinic acid, ornithine, phen-carboxylic acids (7), some of which are unique to this class ylalanine, tryptophan, and tyrosine). Fig. 1 illustrates, inof alkaloid [e.g. (S)-tropic acid]. Others, such as cinnamic abbreviated form, the metabolic relationship of alkaloids toacid and benzoic acid, are more widespread in nature and This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. these precursors. Unlike some classes of natural products,are found in other types of natural products. such as the terpenes, alkaloids are formed by many diverse biosynthetic routes. Biosynthesis of the 1-Methyl-A1- Once the biosynthetic route to a certain al- pyrrolinium Salt kaloid has been elucidated it is tempting to generalize this result to include other alkaloids of the same class. Thus it is All the experimental evidence is consistent now considered that most indole alkaloids containing awith the 1-methyl-A 1-pyrrolinium salt (30) being a precur- monoterpene residue are modifications of strictosidine (3)sor of the tropane nucleus. The various biosynthetic routes derived from tryptamine (1) and secologanin (2), as illus-which have been established for its formation are sum- trated in Fig. 2 (2, 3), even though experimental biosynthe-marized in Fig. 4. Initially it was thought that the double tic work has been carried out on only a small fraction of thebond in the iminium salt could isomerize between its C-2 known monoterpene indole alkaloids. However there canand C-5 positions, which would result in the scrambling of be variations in the way in which an alkaloid skeleton is as- any isotopic label (e.g. 14C) which might be present at either sembled. This is true of the tropane alkaloids and the recentof these positions. However this was shown not to occur in modifications to the generally accepted biosynthesis of this either acidic or basic media (8). Deprotonation of 30 affords 340 PlantaMed. 56(2990) Edward Leete MevalonicAcid Prephenic Acid N Sesquiterpenes (farnesol) Phenyiaianine Tyrosine Polyterpenes (rubber) Triterpenes (aqusiene) Steroids (lanosterol) Cholesterol (cortisone, estrone, Antibiotics vitamin D) (peniciiiin, bacitracin) Antibiotics (erythromycin, tetracycline) Peptides, Proteins, Enzymes Anthraquinonea (insuiin, kerstin. pepsin) Nucleic Acids Flavanoid, Prostaglandins (DNA. RNA) Fig. 1 Biosynthetic relationships of natural products. CHO CH2 ,CH3 ,CH3 iJç]1NH2+ H H3COOCHJ51 E L}CH3) 4d tryptamine (1) secologanin (2) 4 5 tropan. (6) 7 ,CH3 ,CH3 strictosidine t Jr NH CH2 synthase OGtu This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. H1T- H3COOC-0 OH strictosidine (3) tropins (8; tropan-3e-ol) W-tropine (9; tropan—3p—oi) cocaine(1O) Fig. 2 The first step in the biosynthesis of the mono-terpene indole alkaloids. CH3 ,CH3 C5H0HH -OH hyoscyamine (11) scopolamine (12) sobettendine (13) Fig. 3 Structural features of some tropane alkaloids. Recent Developments in the Biosynthesis qftheTropaneAlkaloids Planta Med. 56(1990) 341 COOH COOH COOH COOH COOH Fig.4 Biosynthetic routes to the 1-methyl- A'-pyrrolinium salt (30). Lo '4H [<NH2CHO NH2 protine (14) K reb a COOH COOH cycle ,/CH3COOH e L<NH2COOH 2/NH2 0H r"4'COOH -ketoglutaricacid (15) glutamic acid (16) NH2 NHY NH2 ornlthine (17) 0 NH2 II , NH2 NH2 NH—C—NH2 bound putrescine(18) putrescine (19) 20 NH2 J, f COOH NH—Y NH2 NH—CH3 NH2NH ö-N-methyLornithine (21) NH—CN3 NH—'CH3 NH —NH2 22 (23) agmatine (24) I NH—CH3 NH2 C0 OH OOH NH2 [HO LNH NH—CH3 NH—C-—NH2 a-N-methylornithine (25) 26 arginine (27) OH a— N—CH3 N—CH3 —,. L.Y_CH3 DN_CH3 28 29 30 31 __--v\ -CH3cLc H H3 tH3 CH3 CH3 CH3 (SI-nicotine (32) hygrine (33) cu5cohygrine (34) 35 ' This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. 1 -methy1-2-pyrroline (31) which is in equilibrium with 30, 4-Methylaminobutanal is formed by the The iminium salt 30 is also a precursor of the N-methylpyr-oxidation of N-methylputrescine and the enzyme which rolidine rings of nicotine (32) (8, 9), hygrine (33) (10, 11),catalyzes this oxidation has been isolated from Nicotiana and cuscohygrine (34) (12) as well as hyoscyamine andtabacum (17—21), Datura stramonium (20), and Hyos- other tropane alkaloids. The iminium salt is formed by thecyamus niger (22). The enzyme, N-methylputrescine oxid- cyclization of 4-methylaminobutanal (26) via the car-ase, isolated from tobacco roots, was not specific for N- binolamine, 2-hydroxy- I -methylpyrrolidine (29). 1 -Meth-methylputrescine. Other diamines such as putrescine and yl-2-pyrrolidinone (28) has been detected in Atropa bel-cadaverine (1,5-diaminopentane) were oxidized to 4- ladonna (13, 14) and is plausibly formed by oxidation of theaminobutanal and 5 -aminopentanal, respectively. carbinolamine. 1-Methylpyrrolidine (35) which is a minor alkaloid of Atropa belladonna (15) and tobacco (16) is pre- The stereochemistry of the oxidation of N- sumably formed by the reduction of the iminium salt 30.methylputrescine has been studied in Nicotiana tabacum Labeled 4-methylaminobutanal was detected in Datura(23) and it was established that it is the pro-S hydrogen stramonium plants which had been fed [2-14C]ornithine (9). which is lost from the carbon carrying the primary amino 342 PlantaMed. 56(1990) Edward Leete H2N NH2 DR [LR_2H[putrescine (36) H3C—HN''NH2 H2N1 NH—CH3 H000 NH2 NH—OH3 H2N NH2 0 DR e-N-methylornithine (21) putrescine (19) I Loss of pro-S hydrogen H2Nk1HCH3 H3C—HN i 0-:-LNHCH3 D 37 I I HI D N xe OH3 OH3 OH3 I /30\ 1OH>O_H D.CH3 OH3 CS) — [SR — 2HJ n i cot n e CS) —[2 - 2H ]n i c otin e 51- nicotine (32) hyoscyamine (11) Fig. 5 Stereochemistry of the oxidation of N-methylputrescine. Fig. 6 The mode of incorporation of ô-N-methylornithine into nicotine and hyoscyamine. group,during its oxidation to the aldehyde. This result wasdefinitelythe case in Nicotiana species (28) since the deduced by using [1R-2Hltputrescine (36,Fig.5), as a sub- nicotine derived from the [2-14C,N-methyl-14C1-ó-N-meth- strate. The location of deuterium in the ultimate nicotineylornithine was labeled only at its C-2' and N-methyl posi- was determined by 2H-NMR spectroscopy. N-Methylputres-tions, (Fig. 6). This result is inconsistent with feedings of un- cine has been established as a direct precursor of the imin-symmetrically labeled ornithine to tobacco. In all cases the ium salt and the alkaloids derived from it (24—26). As ex-pyrrolidine ring of nicotine was labeled symmetrically (29). pected, it is incorporated unsymmetrically into the ultimate These results indicate that unsymmetrically labeled or- alkaloids. For example, [1-13C, 14C, 1-15N]-N-methylputres- nithine such as [2-14Clornithine is decarboxylated to pu- cine (37) afforded nicotine which was labeled solely at its C- trescine prior to N-methylation. Attempts to show the pres- 5' position with 13C and 14C and with 15N on its pyrrolidineence of ô-N-methylornithine in Datura species have also nitrogen. This same precursor was incorporated unsym-been unsuccessful (30). It also could not be detected in metrically into the tropane moiety of scopolamine inDaturalabeled form when [5-'4C]ornithine was administered to a innoxia (24).
Load more

Recommended publications
  • Download Author Version (PDF)
    Organic & Biomolecular Chemistry Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/obc Page 1 of 26 Organic & Biomolecular Chemistry Comparison of alternative nucleophiles for Sortase A-mediated bioconjugation and application in neuronal cell labelling Samuel Baera, Julie Nigro a,b, Mariusz P. Madej a, Rebecca M. Nisbet a,b, Randy Suryadinata a, Gregory Coia a, Lisa P. T. Hong a, Timothy E. Adams a, Charlotte C. Williams *a†, Stewart D. Nuttall a,b†. Manuscript aCSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria, 3052, AUSTRALIA. bPreventative Health Flagship, 343 Royal Parade, Parkville, Victoria, 3052, AUSTRALIA. *Correspondence to: Charlotte C. Williams ([email protected] ) at CSIRO Materials Accepted Science and Engineering, 343 Royal Parade, Parkville, Victoria, 3052, AUSTRALIA; Ph: +61 3 9662 7100).
    [Show full text]
  • APPENDIX G Acid Dissociation Constants
    harxxxxx_App-G.qxd 3/8/10 1:34 PM Page AP11 APPENDIX G Acid Dissociation Constants §␮ ϭ 0.1 M 0 ؍ (Ionic strength (␮ † ‡ † Name Structure* pKa Ka pKa ϫ Ϫ5 Acetic acid CH3CO2H 4.756 1.75 10 4.56 (ethanoic acid) N ϩ H3 ϫ Ϫ3 Alanine CHCH3 2.344 (CO2H) 4.53 10 2.33 ϫ Ϫ10 9.868 (NH3) 1.36 10 9.71 CO2H ϩ Ϫ5 Aminobenzene NH3 4.601 2.51 ϫ 10 4.64 (aniline) ϪO SNϩ Ϫ4 4-Aminobenzenesulfonic acid 3 H3 3.232 5.86 ϫ 10 3.01 (sulfanilic acid) ϩ NH3 ϫ Ϫ3 2-Aminobenzoic acid 2.08 (CO2H) 8.3 10 2.01 ϫ Ϫ5 (anthranilic acid) 4.96 (NH3) 1.10 10 4.78 CO2H ϩ 2-Aminoethanethiol HSCH2CH2NH3 —— 8.21 (SH) (2-mercaptoethylamine) —— 10.73 (NH3) ϩ ϫ Ϫ10 2-Aminoethanol HOCH2CH2NH3 9.498 3.18 10 9.52 (ethanolamine) O H ϫ Ϫ5 4.70 (NH3) (20°) 2.0 10 4.74 2-Aminophenol Ϫ 9.97 (OH) (20°) 1.05 ϫ 10 10 9.87 ϩ NH3 ϩ ϫ Ϫ10 Ammonia NH4 9.245 5.69 10 9.26 N ϩ H3 N ϩ H2 ϫ Ϫ2 1.823 (CO2H) 1.50 10 2.03 CHCH CH CH NHC ϫ Ϫ9 Arginine 2 2 2 8.991 (NH3) 1.02 10 9.00 NH —— (NH2) —— (12.1) CO2H 2 O Ϫ 2.24 5.8 ϫ 10 3 2.15 Ϫ Arsenic acid HO As OH 6.96 1.10 ϫ 10 7 6.65 Ϫ (hydrogen arsenate) (11.50) 3.2 ϫ 10 12 (11.18) OH ϫ Ϫ10 Arsenious acid As(OH)3 9.29 5.1 10 9.14 (hydrogen arsenite) N ϩ O H3 Asparagine CHCH2CNH2 —— —— 2.16 (CO2H) —— —— 8.73 (NH3) CO2H *Each acid is written in its protonated form.
    [Show full text]
  • Duboisia Myoporoides
    Principal Studies on Scopolamine Biosynthesis in Duboisia spec. for Heterologous Reconstruction of Tropane Alkaloid Biosynthesis Laura Kohnen1, Friederike Ullrich1, Nils J. H. Averesch2 and Oliver Kayser1 (1) Technical Biochemistry, Technical University Dortmund, Dortmund, Germany (2) Centre for Microbial Electrochemical Systems (CEMES), The University of Queensland, Brisbane, Australia [email protected], [email protected], [email protected], [email protected] Tropane alkaloids Objectives - Tropane alkaloids (TA), including scopolamine and hyoscyamine, are - Reconstruction of a heterologous pathway requires fundamental secondary plant components mainly occurring in the family of Solanaceae understanding of the merging pathways, the respective biosynthetic genes, - Scopolamine is an important bulk compound in the semi-synthesis of drugs their transcription and regulation - here we focus on: for clinical medicines like Buscopan® or Spiriva® I) Analysis of the principal pathway and most important enzymes for their - TA are mainly obtained via extraction from field-grown Duboisia hybrids expression and biochemical profile - Demand for scopolamine based drugs is expected to increase in the future II) Construction of a cDNA library from cytosolic root cells of Duboisia - A biotechnological process may help to compensate fluctuations in crop yield species of the medicinal plants III) Analysis of metabolic profiles of Duboisia species Introduction IV) In silico analysis of a heterologous production system utilizing metabolic network modelling Biosynthetic pathway of TA NMR-based metabolomics - Biosynthesis of TA is located in the roots[1] - Global analysis of leaf and root extracts - TA are transported to the aerial parts of the plants - Detection of primary (amino acids, sugars) as well as secondary metabolites - Storage and accumulation of hyoscyamine, 6-OH-hyoscyamine and (flavonoids, TA) scopolamine in the leaves (cf.
    [Show full text]
  • Chapter 2 2. Q Labelling in Hyoscyamine
    Durham E-Theses The biosynthesis of the tropane alkaloid hyoscyamine in datura stramonium Wong, Chi W. How to cite: Wong, Chi W. (1999) The biosynthesis of the tropane alkaloid hyoscyamine in datura stramonium, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/4310/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk COPYRIGHT The copyright of this thesis rests with the author. No quotation form it should be published without prior consent, and any information derived from this thesis should be acknowledged. DECLARATION The work contained in this thesis was carried out in the Department of Chemistry at the University of Durham between October 1995 and September 1998. All the work was carried out by the author, unless otherwise indicated. It has not been previously submitted for a degree at this or any other university.
    [Show full text]
  • Tropane and Granatane Alkaloid Biosynthesis: a Systematic Analysis
    Office of Biotechnology Publications Office of Biotechnology 11-11-2016 Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Neill Kim Texas Tech University Olga Estrada Texas Tech University Benjamin Chavez Texas Tech University Charles Stewart Jr. Iowa State University, [email protected] John C. D’Auria Texas Tech University Follow this and additional works at: https://lib.dr.iastate.edu/biotech_pubs Part of the Biochemical and Biomolecular Engineering Commons, and the Biotechnology Commons Recommended Citation Kim, Neill; Estrada, Olga; Chavez, Benjamin; Stewart, Charles Jr.; and D’Auria, John C., "Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis" (2016). Office of Biotechnology Publications. 11. https://lib.dr.iastate.edu/biotech_pubs/11 This Article is brought to you for free and open access by the Office of Biotechnology at Iowa State University Digital Repository. It has been accepted for inclusion in Office of Biotechnology Publicationsy b an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Abstract The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring ot their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis.
    [Show full text]
  • Utilization of Anthranilic and Nitrobenzoic Acids by Nocardia Opaca and a Flavobacteriurn
    J. gen. Microbial. (1966),42, 219-235 Printed in Great Britain Utilization of Anthranilic and Nitrobenzoic Acids by Nocardia opaca and a Flavobacteriurn BY R. B. CAIN Depadnaent of Microbiology, OkEahoma State University, Stillwater, Oklahoma, U.S.A. and Department of Botany, University of Newcastle upon Tyne” (Received 11 May 1965, accepted 16 September 1965) SUMMARY Anthranilic and o-nitrobenzoic acids act as mutual inhibitors of both growth and substrate oxidation for Nocardia opaca and a flavobacterium which can utilize either substance as sole source of carbon, nitrogen and energy, Growth of the former bacterium on anthranilate induced, appar- ently simultaneously, both the transport system for anthranilate uptake and the enzymic mechanism necessary for its complete oxidation to CO, and NH3. Among the enzymes induced by anthranilate was the complete sequence that oxidizes catechol to /3-oxoadipate; this was absent from organisms grown in fumarate or glucose media. The properties of the first enzyme in this sequence, a catechol-l,2-oxygenase, differ in several features from those of the same enzyme induced in this bacterium by growth on o-nitrobenzoic acid. INTRODUCTION Anthranilic (o-aminobenzoic) acid is an important intermediary metabolite in both biosynthetic and catabolic pathways in micro-organisms. It serves for in- stance as a precursor for tryptophan in Aerobacter aerogews and Escherichia coli (Doy & Gibson, 1961), in Nmrospora CT~SSQ(Yanofsky, 1956; Yanofsky & Rach- meler, 1958) and in saccharomyces mutants (Lingens, Hildinger & Hellman, 1958). Hydroxylation of anthranilic acid, in the 3-position, has been observed with rat liver preparations (Wiss & Hellman, 1953) but no hydroxylation of anthranilic acid has been conclusively demonstrated in micro-organisms.
    [Show full text]
  • Chemicals Required for the Illicit Manufacture of Drugs Table 1 SUBSTANCES in TABLES I and II of the 1988 CONVENTION
    Chemicals Required 1. A variety of chemicals are used in the illicit manufacture of for the Illicit drugs. The United Nations Convention against Illicit Traffic in Manufacture of Drugs Narcotic Drugs and Psychotropic Substances of 1988 (1988 Convention) refers to “substances frequently used in the illicit manufacture of narcotic drugs and psychotropic substances”. Twenty-two such substances are listed in Tables I and II of the 1988 Convention as in force on 1st May, 1998. (See Table1) Table 1 Table I Table II SUBSTANCES IN N-Acetylanthranilic acid. Acetic anhydride TABLES I AND II OF Ephedrine Acetone THE 1988 Ergometrine Anthranilic acid CONVENTION Ergotamine Ethyl ether Isosafrole Hydrochloric acid* Lysergic acid Methyl ethyl ketone 3,4-methylenedioxyphenyl-2-propanone Phenylacetic acid 1-phenyl-2-propanone Piperidine Piperonal Potassium permanganate Pseudoephedrine Sulphuric acid* Safrole Toluene The salts of the substances in this Table The salts of the substances whenever the existence of such salts is in this Table whenever the possible. existence of such salts is possible. * The salts of hydrochloric acid and sulphuric acid are specifically excluded from Table II. U N D C P 11 The term “precursor” is used to indicate any of these substances in the two Tables. Chemicals used in the illicit manufacture of narcotic drugs and psychotropic substances are often described as precursors or essential chemicals, and these include true precursors, solvents, oxidising agents and other Chemicals used in the illicit manufacture of narcotic substances. Although the term is not drugs and psychotropic substances are often technically correct, it has become common described as precursors or essential chemicals, and practice to refer to all such substances as these include true precursors, solvents, oxidising “precursors”.
    [Show full text]
  • PEREGRINO-THESIS-2017.Pdf (6.329Mb)
    Biochemical studies in the elucidation of genes involved in tropane alkaloid production in Erythroxylum coca and Erythroxylum novogranatense by Olga P. Estrada, B. S. A Thesis In Chemical Biology Submitted to the Graduate Faculty of Texas Tech University in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCES Approved Dr. John C. D’Auria Chair of Committee Dr. David W. Nes Co-chair of Committee Mark Sheridan Dean of the Graduate School May, 2017 Copyright 2017, Olga P. Estrada Texas Tech University, Olga P. Estrada, May 2017 AKNOWLEDGMENTS I would like to thank my mentor and advisor Dr. John C. D’Auria, for providing me with the tools to become a scientist, and offering me his unconditional support. Thanks to the members of the D’Auria lab, especially Neill Kim and Benjamin Chavez for their aid during my experimental studies. And of course, thank you to my family for always giving me the strength to pursue my goals. ii Texas Tech University, Olga P. Estrada, May 2017 TABLE OF CONTENTS AKNOWLEDGMENTS ........................................................................................................... ii ABSTRACT ........................................................................................................................... v LIST OF TABLES ................................................................................................................. vi LIST OF FIGURES ............................................................................................................... vii CHAPTER I .........................................................................................................................
    [Show full text]
  • Role of Cadaverine and Piperidine in the Formation of N-Nitrosopiperidine in Heated Cured Meat
    ROLE OF CADAVERINE AND PIPERIDINE IN THE FORMATION OF N-NITROSOPIPERIDINE IN HEATED CURED MEAT Drabik-Markiewicz G.1, 2, De Mey E. 1, Impens S. 1, Kowalska T. 2, Vander Heyden Y. 3 and Paelinck H.1* 1Research Group for Technology and Quality of Animal Products, Catholic University College Gent, Technology Campus Gent, Department of Chemistry and Biochemistry, 1 Gebroeders Desmetstraat, 9000 Gent, Belgium 2University of Silesia, Institute of Chemistry, 9 Szkolna Street, 40-006 Katowice, Poland 3Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium *Corresponding author (e-mail: [email protected]) Abstract — N-nitrosamines are carcinogenic compounds, which formation in meat products depends from different factors e.g., temperature, storage time, precursors and/or added sodium nitrite. Sodium nitrite is important for meat processing as curing agent. The aim of this study was to determine the role of cadaverine and piperidine on the formation of N-nitrosamines in heated cured meat products. Such experimental products were processed with different amounts of sodium nitrite ( 0 mg kg -1, 120 mg kg -1, 480 mg kg -1), 1000 mg kg -1 of cadaverine or 10 mg kg -1 of piperidine, and heated at 85°C, 120°C, 160°C or 220°C. Experimental evidence was produced using gas chromatography in combination with Thermal Energy Analyzer (GC-TEA). The obtained analytical results were statistically evaluated by means of the Univariate Analysis of Variance (ANOVA) approach. In the current study only N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) were detected.
    [Show full text]
  • Article the Bee Hemolymph Metabolome: a Window Into the Impact of Viruses on Bumble Bees
    Article The Bee Hemolymph Metabolome: A Window into the Impact of Viruses on Bumble Bees Luoluo Wang 1,2, Lieven Van Meulebroek 3, Lynn Vanhaecke 3, Guy Smagghe 2 and Ivan Meeus 2,* 1 Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou, China; [email protected] 2 Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; [email protected], [email protected] 3 Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Vet- erinary Medicine, Ghent University, Merelbeke, Belgium; [email protected]; [email protected] * Correspondence: [email protected] Selection of the targeted biomarker set: In total we identified 76 metabolites, including 28 amino acids (37%), 11 carbohy- drates (14%), 11 carboxylic acids, 2 TCA intermediates, 4 polyamines, 4 nucleic acids, and 16 compounds from other chemical classes (Table S1). We selected biologically-relevant biomarker candidates based on a three step approach: (1) their expression profile in stand- ardized bees and its relation with viral presence, (2) pathways analysis on significant me- tabolites; and (3) a literature search to identify potential viral specific signatures. Step (1) and (2), pathways analysis on significant metabolites We performed two-way ANOVA with Tukey HSD tests for post-hoc comparisons and used significant metabolites for metabolic pathway analysis using the web-based Citation: Wang, L.L.; Van platform MetaboAnalyst (http://www.metaboanalyst.ca/) in order to get insights in the Meulebroek, L.; Vanhaecke.
    [Show full text]
  • Dietary Supplementation of Inorganic, Organic, and Fatty Acids in Pig: a Review
    animals Review Dietary Supplementation of Inorganic, Organic, and Fatty Acids in Pig: A Review Giulia Ferronato * and Aldo Prandini Department of Animal Sciences, Food and Nutrition (DIANA), Faculty of Agriculture, Food and Environmental Science, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29100 Piacenza, Italy; [email protected] * Correspondence: [email protected] Received: 14 August 2020; Accepted: 18 September 2020; Published: 25 September 2020 Simple Summary: The role of acids in pig feed strategies has changed from feed acidifier and preservative to growth promoter and antibiotics substitute. Since the 2006 European banning of growth promoters in the livestock sector, several feed additives have been tested with the goal of identifying molecules with the greatest beneficial antimicrobial, growth-enhancing, or disease-preventing abilities. These properties have been identified among various acids, ranging from inexpensive inorganic acids to organic and fatty acids, and these have been widely used in pig production. Acids are mainly used during the weaning period, which is considered one of the most critical phases in pig farming, as well as during gestation, lactation, and fattening. Such supplementation generally yields improved growth performance and increased feed efficiency; these effects are the consequences of different modes of action acting on the microbiome composition, gut mucosa morphology, enzyme activity, and animal energy metabolism. Abstract: Reduction of antibiotic use has been a hot topic of research over the past decades. The European ban on growth-promoter use has increased the use of feed additivities that can enhance animal growth performance and health status, particularly during critical and stressful phases of life.
    [Show full text]
  • Free-Amino Acid Metabolic Profiling of Visceral Adipose Tissue from Obese
    Amino Acids (2020) 52:1125–1137 https://doi.org/10.1007/s00726-020-02877-6 ORIGINAL ARTICLE Free‑amino acid metabolic profling of visceral adipose tissue from obese subjects M. C. Piro1 · M. Tesauro2 · A. M. Lena1 · P. Gentileschi3 · G. Sica3 · G. Rodia2 · M. Annicchiarico‑Petruzzelli4 · V. Rovella2 · C. Cardillo5 · G. Melino1,6 · E. Candi1,4 · N. Di Daniele2 Received: 14 October 2019 / Accepted: 26 July 2020 / Published online: 5 August 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020 Abstract Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defned as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardio- vascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43–48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identifed as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/ mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation prod- ucts are increased.
    [Show full text]