DOCSLIB.ORG

HGT in the Human and Skin Commensal Malassezia: a Bacterially Derived Flavohemoglobin Is Required for NO Resistance and Host Interaction

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
HGT in the Human and Skin Commensal Malassezia: a Bacterially Derived Flavohemoglobin Is Required for NO Resistance and Host Interaction HGT in the human and skin commensal Malassezia: A bacterially derived flavohemoglobin is required for NO resistance and host interaction Giuseppe Ianiria,1, Marco A. Coelhoa, Fiorella Ruchtib, Florian Sparberb, Timothy J. McMahonc,CiFua, Madison Bolejackd,e, Olivia Donovane,f, Hayden Smutneye,f, Peter Mylere,g,h,i, Fred Dietricha, David Fox IIId,e, Salomé LeibundGut-Landmannb, and Joseph Heitmana,2 aDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; bSection of Immunology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland; cDepartment of Medicine, Veterans Affairs Medical Center, Durham, NC 27705; dUnion Chimique Belge Pharma, Bainbridge Island, WA 98110; eSeattle Structural Genomics Center for Infectious Disease, Seattle, WA 98101; fUnion Chimique Belge Pharma, Bedford, MA 01730; gCenter for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA 98101; hDepartment of Biomedical Information and Medical Education, University of Washington, Seattle, WA 98195; and iDepartment of Global Health, University of Washington, Seattle, WA 98195 Edited by Jay C. Dunlap, Geisel School of Medicine, Dartmouth College, Hanover, NH, and approved May 18, 2020 (received for review February 26, 2020) The skin of humans and animals is colonized by commensal and disease in patients with CARD9 mutations, and in accelerating pathogenic fungi and bacteria that share this ecological niche and the progression of pancreatic adenocarcinoma in murine models have established microbial interactions. Malassezia are the most and in humans, and cystic fibrosis pulmonary exacerbation (6–8). abundant fungal skin inhabitant of warm-blooded animals and Nitric oxide (NO) is a reactive compound of central importance have been implicated in skin diseases and systemic disorders, in- in biological systems and it functions both as a signaling and toxic cluding Crohn’s disease and pancreatic cancer. Flavohemoglobin is molecule. While little is known about NO synthesis in fungi, in a key enzyme involved in microbial nitrosative stress resistance mammals NO is synthesized by NO synthases (NOS isoforms). and nitric oxide degradation. Comparative genomics and phyloge- NOS1 and NOS3 are constitutively expressed in neurons and en- netic analyses within the Malassezia genus revealed that dothelium, respectively, and produce NO to promote S-nitrosylation flavohemoglobin-encoding genes were acquired through indepen- and transcriptional regulation. S-nitrosylation is a posttranslational MICROBIOLOGY dent horizontal gene transfer events from different donor bacteria mechanism involving oxidative modification of cysteine by NO, that are part of the mammalian microbiome. Through targeted gene deletion and functional complementation in Malassezia sym- Significance podialis, we demonstrated that bacterially derived flavohemoglo- bins are cytoplasmic proteins required for nitric oxide detoxification Malassezia and nitrosative stress resistance under aerobic conditions. RNA- species are the main fungal components of the sequencing analysis revealed that endogenous accumulation of mammalian skin microbiome and are associated with a number Malassezia nitric oxide resulted in up-regulation of genes involved in stress of skin disorders. Recently, has also been found in ’ response and down-regulation of the MalaS7 allergen-encoding association with Crohn s disease and with pancreatic cancer. genes. Solution of the high-resolution X-ray crystal structure of The elucidation of the molecular bases of skin adaptation by Malassezia Malassezia flavohemoglobin revealed features conserved with both is critical to understand its role as commensal and bacterial and fungal flavohemoglobins. In vivo pathogenesis is in- pathogen. In this study we employed evolutionary, molecular, dependent of Malassezia flavohemoglobin. Lastly, we identified an biochemical, and structural analyses to demonstrate that the Malassezia additional 30 genus- and species-specific horizontal gene transfer bacterially derived flavohemoglobins acquired by candidates that might have contributed to the evolution of this through horizontal gene transfer resulted in a gain of function genus as the most common inhabitants of animal skin. critical for nitric oxide detoxification and resistance to nitro- sative stress. Our study underscores horizontal gene transfer as Malassezia Malassezia | flavohemoglobin | horizontal gene transfer an important force modulating evolution and niche adaptation. he skin microbiome includes numerous microorganisms that Author contributions: G.I., S.L.-L., and J.H. designed research; G.I., M.A.C., F.R., F.S., C.F., Testablish a variety of direct and indirect interactions char- M.B., O.D., and H.S. performed research; G.I., T.J.M., P.M., D.F., and S.L.-L. contributed acterized by the exchange of genetic material that impact mi- new reagents/analytic tools; G.I., M.A.C., F.R., F.S., C.F., M.B., F.D., D.F., and S.L.-L. ana- crobial biology, contributing to their speciation and evolution. lyzed data; and G.I. wrote the paper with contributions from M.A.C., M.B., D.F., S.L.-L., and J.H. Malassezia is the most abundant fungal genus resident on human The authors declare no competing interest. skin, representing more than 90% of the skin mycobiome (1). This genus presently consists of 18 diverse species (2), each with This article is a PNAS Direct Submission. an unusually compact genome that underwent extensive gene Published under the PNAS license. turnover events as a result of evolutionary adaptation and col- Data deposition: The sequence data generated in this study have been submitted to the National Center for Biotechnology Information under BioProject accession number onization to a nutrient-limited ecological niche such as the skin PRJNA626605. Individual accession numbers are SRR11574550 for RNA-seq reads of (3). Although commensals, Malassezia species are also associated Malassezia WT untreated control samples; SRR11574549 for RNA-seq reads of Malassezia with a number of clinical skin disorders, including pityriasis WT NO-treated samples; and SRR11574548 for RNA-seq Malassezia yhb1Δ mutant. The final structure factors and coordinates of the flavohemolgobin Yhb101 of Malassezia yamatoensis versicolor, dandruff, and atopic dermatitis (AD) (4). A recently have been deposited in the Protein Data Bank (PDB) under code 6O0A. developed epicutaneous murine model revealed that the host 1Present address: Department of Agricultural, Environmental and Food Sciences, Univer- responses to Malassezia are dominated by proinflammatory cy- sity of Molise, 86100 Campobasso, Italy. tokine IL-17 and related factors that prevent fungal overgrowth 2To whom correspondence may be addressed. Email: [email protected]. and exacerbate inflammation under atopy-like conditions (5). This article contains supporting information online at https://www.pnas.org/lookup/suppl/ Furthermore, Malassezia species have also been implicated re- doi:10.1073/pnas.2003473117/-/DCSupplemental. cently as causal agents of Crohn’s disease/inflammatory bowel www.pnas.org/cgi/doi/10.1073/pnas.2003473117 PNAS Latest Articles | 1of11 Downloaded by guest on September 25, 2021 and this is the central NO-mediated signaling mechanism that and whether it had a fungal or bacterial origin. BLAST analyses affects myriad of cellular physiological and pathophysiological with the M. globosa Yhb1 sequence as query identified a single processes (9). On the other hand, NOS2 is not constitutively copy of YHB1 in all Malassezia species and strains with sequenced expressed but is induced in inflammatory cells in response to in- genomes. Intriguingly, this comparative search revealed that the fection and is involved in wound healing, immune regulation, and best hits in Malassezia yamatoensis and Malassezia slooffiae had host defense (10). lower E values (5e-64 and 1e-59, respectively) compared to the In fungi, NO is synthesized through a reductive denitrification remaining Malassezia species (E values ranging from 0.0 to 7e- pathway from nitrite, and through an oxidative pathway from 161), possibly suggesting different origins or modifications of L-arginine, although the detailed biochemical mechanisms have these flavohemoglobin-encoding genes. To elucidate the evolu- not yet been fully elucidated (11–13). Compared to mammals, tionary trajectory of flavohemoglobin within the whole Malassezia plants, and bacteria, the role of NO in fungal biology is under- genus, a maximum likelihood (ML) phylogenetic tree was recon- studied. In Saccharomyces cerevisiae NO is important for acti- structed using >2,000 Yhb1 bacterial and fungal sequences vation of transcription factors that are involved in resistance to a retrieved from GenBank. This phylogenetic analysis revealed two variety of environmental stress conditions, such as oxidative clades of flavohemoglobin within the Malassezia genus: clade 1 stress, heat shock, and hydrostatic pressure (11). Other studies that includes 13 species and clusters together with Brevi- report an involvement of NO in pathogenesis of Botrytis cinerea bacterium species belonging to Actinobacteria; and clade 2 that and Magnaporthe oryzae, in morphogenesis and reproduction in includes M. yamatoensis and M. slooffiae and clusters together Aspergillus nidulans, and in the yeast-to-hyphae dimorphic tran- with different Actinobacteria, with the closest relative being sition in Candida albicans (12, 14, 15). Kocuria kristinae (Fig. 1 A–C). To evaluate the statistical
Load more

Recommended publications
  • Phylogenetic Screening for Possible Novel
    11 M060072591U NORTH-WEST UNIVERSITY tilt• YUNIBESITI YA BOKONE•BOPHIRIMA NOOROVVE S-UNIVERSITEIT PHYLOGENETIC SCREENING FOR POSSIBLE NOVEL ANTIBIOTIC PRODUCING ACTINOMYCETES FROM RHIZOSPHERIC SOIL SAMPLES COLLECTED FROM NGAKA MODIRI MOLEMA DISTRICT IN NORTH WEST PROVINCE, SOUTH AFRICA I BY MOBOLAJI FELICIA ADEGBOYE A thesis submitted in fulfilment of the requirements for the degree of DOCTOR OF PHILOSOPHY (BIOLOGY) DEPARTMENT OF BIOLOGICAL SCIENCES FACULTY OF SCIENCE, AGRICULTURE AND TECHNOLOGY NORTH-WEST UNIVERSITY, MAFIKENG CAMPUS SOUTH AFRICA Supervisor: Professor Olubukola 0. Babalola 2014 LIBRARY o MAFIKENG CAMPUS CALL NO.: 2021 -02- 0 4 DECLARATION I, the undersigned, declare that this thesis submitted to the North-West University for the degree of Doctor of Philosophy in Biology in the Faculty of Science, Agriculture and Technology, School of Environmental and Health Sciences, and the work contained herein is my original work with exemption to the citations and that this work has not been submitted at any other University in partial or entirely for the award of any degree. Name: Mobolaji Felicia Adegboye Signature: .....~ •·· ··· ····· ·· .. ··············· ..... Date: .... ~S.. .. ....a~ ·1·· ·'.}Q~i; ... ............ .... DEDICATION This work is dedicated to Almighty God for His faithfulness over my life and for making my helpers to be many. ii ACKNOWLEDGEMENTS I would like to express my deepest thanks, gratitude and appreciation to my supervisor and mentor, Prof. Olubukola 0. Babalola for giving me the opportunity to pursue my doctoral degree under her supervision and for her encouragement, help and kind support. Her invaluable advice, suggestions, discussions and guidance were a real support to me. I acknowledge with honour and gratitude the International Foundation for Science (IFS) for research grant (F/5330-1 ), Connect Africa Scholarship Award, H3ABioNet/SANBio Scholarship and North-West University for offering me bursary/scholarship award to pursue the PhD degree.
    [Show full text]
  • Electronic Supplementary Material (ESI) for Analyst. This Journal Is © the Royal Society of Chemistry 2017
    Electronic Supplementary Material (ESI) for Analyst. This journal is © The Royal Society of Chemistry 2017 Supplemental Table 2. Proteins Increased in Either Blood or Horizon media Table 2A. Proteins Increased in Spores Produced on Horizon Soil Over Spores Produced on Blood Medium quasi.fdr Protein Protein Class/Name KEGG Pathway Names or Function (if ID Pathways found in KEGG) Amino Acid Metabolism bat00250, bat00280, Alanine, aspartate and glutamate metabolism, bat00410, Valine, leucine and isoleucine degradation, bat00640, beta-Alanine metabolism to acetyl CoA, 4.50E-07 BAS0310 4-aminobutyrate aminotransferase bat00650 Propanoate metabolism, Butanoate metabolism bat00270, bat00330, Cysteine and methionine metabolism, Arginine bat00410, and proline metabolism, beta-Alanine 3.84E-10 BAS5060 spermidine synthase bat00480 metabolism, Glutathione metabolism bat00270, bat00330, Cysteine and methionine metabolism, Arginine bat00410, and proline metabolism, beta-Alanine 2.30E-09 BAS5219 spermidine synthase bat00480 metabolism, Glutathione metabolism bat00250, Alanine, aspartate and glutamate metabolism, 6.94E-07 BAS0561 alanine dehydrogenase bat00430 Taurine and hypotaurine metabolism bat00250, Alanine, aspartate and glutamate metabolism, 5.23E-07 BAS4521 alanine dehydrogenase bat00430 Taurine and hypotaurine metabolism 0.005627 BAS5218 agmatinase, putative bat00330 Arginine and proline metabolism 2,3,4,5-tetrahydropyridine-2- carboxylate N-succinyltransferase, 1.40E-10 BAS3891 putative bat00300 Lysine biosynthesis bat00010, bat00020, Glycolysis
    [Show full text]
  • © 2016 Shiliang Tian
    © 2016 Shiliang Tian PROTEIN ENGINEERING USING AZURIN AS THE SCAFFOLD: CAPTURING AND STUDYING NOVEL METAL-SULFENATE AND METAL-NO SPECIES BY SHILIANG TIAN DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2016 Urbana, Illinois Doctoral Committee: Professor Yi Lu, Chair Professor Thomas B. Rauchfuss Professor Wilfred A. van der Donk Assistant Professor Alison R. Fout Abstract Metalloproteins account for nearly half of all proteins in nature. Metal ions play important roles in catalyzing numerous important biological processes that necessary to sustain life on the planet, such as photosynthesis, respiration and nitrogen fixation. Much effort has been made to understand the relationship between structures and functions of metalloproteins. Although significant progresses have been made to obtain the knowledge of how metalloproteins work, the ultimate test is to use this knowledge to design new metallproteins that reproduce the structures and functions of native proteins. Protein redesign strategy is one of the most effective approaches in the design and engineering of artificial metalloenzymes. The advantage of a protein redesign strategy is that it can bypass the problem of developing a stable protein fold because many native proteins have remarkable adaptability for changes. The use of small, stable, easy-to- make, and well-characterized blue copper protein azurin as scaffold to design novel metal binding sites has been proven to be a promising way for protein redesign. Not only can its reduction potential be rationally tuned beyond the nature range via secondary coordination sphere engineering, but also the CuA and redox- active nonheme iron sites have been successfully engineered in azurin.
    [Show full text]
  • Mycobacterium Haemophilum Sp. Nov., a New Pathogen of Humanst
    0020-7713/78/0028-0067$02.0/0 INTERNATIONALJOURNAL OF SYSTEMATICBACTERIOLOGY, Jan. 1978, p. 67-75 Vol. 28, No. 1 Copyright 0 1978 International Association of Microbiological Societies Printed in U.S. A. Mycobacterium haemophilum sp. nov., a New Pathogen of Humanst DAVID SOMPOLINSKY,’v2 ANNIE LAGZIEL,’ DAVID NAVEH,3 AND TULI YANKILEVITZ3 Department of Microbwlogy, Asaf Harofe Government Hospital, Zerifin‘; Rapaport Laboratories, Bar-Ilan University, Ramat-Gan2;and Department of Internal Medicine “A,”Meir Hospital, Kfar Saba,3 Israel A patient under immunosuppressive treatment of Hodgkin’s disease developed generalized skin granulomata and subcutaneous abscesses. Several aspirated pus samples yielded acid-fast rods with the following properties: temperature opti- mum, about 30°C with no growth at 37°C; slow growth (2 to 4 weeks); nonchrom- ogenic; hemoglobin or hemin requirement for growth; catalase negative; pyrazin- amidase and nicotinamidase positive; and urease negative. The guanine-plus- cytosine content of the deoxyribonucleic acid was calculated from the melting temperature to be 66.0 mol%. It is concluded that these isolates belong to a new species, for which the name Mycobacterium haemophilum is proposed. The type strain of this species is strain 1 (= ATCC 29548). The new species is related to M. marinum and M. ulcerans. Granulomatous skin diseases of humans CASE HISTORY caused by mycobacteria other than Mycobacte- After World War 11, a 27-year-old woman was di- rium tuberculosis and M. leprae are well known. agnosed as having tuberculosis. She received treat- The two organisms most often involved etiolog- ment until 1951. In February 1969, at the age of 51, ically are M.
    [Show full text]
  • Supplementary Table 1
    Supplemental Table 1. GO terms for the Flavonoid biosynthesis pathway and genes identified through pathway-level co-expression analysis. The ranking is sorted for descending counts within the pathway. The last two columns give the number of genes within or outside the pathway that are annotated with the term listed in the second column. GO id GO term Genes Genes within outside pathway pathway GO:0008372 cellular component unknown 13 28 GO:0016207 4-coumarate-CoA ligase activity 12 0 GO:0008152 metabolism 8 7 GO:0019350 teichoic acid biosynthesis 8 0 GO:0009234 menaquinone biosynthesis 8 0 GO:0009698 phenylpropanoid metabolism 7 0 GO:0009813 flavonoid biosynthesis 7 0 GO:0008299 isoprenoid biosynthesis 6 0 GO:0009507 chloroplast 5 24 GO:0009411 response to UV 4 0 GO:0016706 "oxidoreductase activity, acting on paired donors, with 4 0 incorporation or reduction of molecular oxygen, 2- oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors" GO:0009058 biosynthesis 3 2 GO:0009699 phenylpropanoid biosynthesis 3 1 GO:0008415 acyltransferase activity 3 1 GO:0004315 3-oxoacyl-[acyl-carrier protein] synthase activity 3 0 GO:0006633 fatty acid biosynthesis 3 0 GO:0005739 mitochondrion 2 7 GO:0005783 endoplasmic reticulum 2 1 GO:0009695 jasmonic acid biosynthesis 2 1 GO:0009611 response to wounding 2 1 GO:0005506 iron ion binding 2 1 GO:0016216 isopenicillin-N synthase activity 2 0 GO:0005777 peroxisome 2 0 GO:0045430 chalcone isomerase activity 2 0 GO:0009705 vacuolar membrane (sensu Magnoliophyta) 2 0 GO:0004321
    [Show full text]
  • Control Engineering Perspective on Genome-Scale Metabolic Modeling
    Control Engineering Perspective on Genome-Scale Metabolic Modeling by Andrew Louis Damiani A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama December 12, 2015 Key words: Scheffersomyces stipitis, Flux Balance Analysis, Genome-scale metabolic models, System Identification Framework, Model Validation, Phenotype Phase Plane Analysis Copyright 2015 by Andrew Damiani Approved by Jin Wang, Chair, Associate Professor of Chemical Engineering Q. Peter He, Associate Professor of Chemical Engineering, Tuskegee University Thomas W. Jeffries, Professor of Bacteriology, Emeritus; University of Wisconsin-Madison Allan E. David, Assistant Professor of Chemical Engineering Yoon Y. Lee, Professor of Chemical Engineering Abstract Fossil fuels impart major problems on the global economy and have detrimental effects to the environment, which has caused a world-wide initiative of producing renewable fuels. Lignocellulosic bioethanol for renewable energy has recently gained attention, because it can overcome the limitations that first generation biofuels impose. Nonetheless, in order to have this process commercialized, the biological conversion of pentose sugars, mainly xylose, needs to be improved. Scheffersomyces stipitis has a physiology that makes it a valuable candidate for lignocellulosic bioethanol production, and lately has provided genes for designing recombinant Saccharomyces cerevisiae. In this study, a system biology approach was taken to understand the relationship of the genotype to phenotype, whereby genome-scale metabolic models (GSMMs) are used in conjunction with constraint-based modeling. The major restriction of GSMMs is having an accurate methodology for validation and evaluation. This is due to the size and complexity of the models.
    [Show full text]
  • Discovery of an Alternate Metabolic Pathway for Urea Synthesis in Adult Aedes Aegypti Mosquitoes
    Discovery of an alternate metabolic pathway for urea synthesis in adult Aedes aegypti mosquitoes Patricia Y. Scaraffia*†‡, Guanhong Tan§, Jun Isoe*†, Vicki H. Wysocki*§, Michael A. Wells*†, and Roger L. Miesfeld*† Departments of §Chemistry and *Biochemistry and Molecular Biophysics and †Center for Insect Science, University of Arizona, Tucson, AZ 85721-0088 Edited by Anthony A. James, University of California, Irvine, CA, and approved December 4, 2007 (received for review August 27, 2007) We demonstrate the presence of an alternate metabolic pathway We previously reported that mosquitoes dispose of toxic for urea synthesis in Aedes aegypti mosquitoes that converts uric ammonia through glutamine (Gln) and proline (Pro) synthesis, acid to urea via an amphibian-like uricolytic pathway. For these along with excretion of ammonia, uric acid, and urea (20). By studies, female mosquitoes were fed a sucrose solution containing using labeled isotopes and mass spectrometry techniques (21), 15 15 15 15 15 NH4Cl, [5- N]-glutamine, [ N]-proline, allantoin, or allantoic we have recently determined how the N from NH4Cl is acid. At 24 h after feeding, the feces were collected and analyzed incorporated into the amide side chain of Gln, and then into Pro, in a mass spectrometer. Specific enzyme inhibitors confirmed that in Ae. aegypti (22). In the present article we demonstrate that the 15 15 15 mosquitoes incorporate N from NH4Cl into [5- N]-glutamine nitrogen of the amide group of Gln contributes to uric acid and use the 15N of the amide group of glutamine to produce synthesis in mosquitoes and, surprisingly, that uric acid can be 15 labeled uric acid.
    [Show full text]
  • The Role of Malassezia Spp. in Atopic Dermatitis
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2015 The role of Malassezia spp. in atopic dermatitis Glatz, Martin ; Bosshard, Philipp P ; Hoetzenecker, Wolfram ; Schmid-Grendelmeier, Peter Abstract: Malassezia spp. is a genus of lipophilic yeasts and comprises the most common fungi on healthy human skin. Despite its role as a commensal on healthy human skin, Malassezia spp. is attributed a pathogenic role in atopic dermatitis. The mechanisms by which Malassezia spp. may contribute to the pathogenesis of atopic dermatitis are not fully understood. Here, we review the latest findings on the pathogenetic role of Malassezia spp. in atopic dermatitis (AD). For example, Malassezia spp. produces a variety of immunogenic proteins that elicit the production of specific IgE antibodies and may induce the release of pro-inflammatory cytokines. In addition, Malassezia spp. induces auto-reactive T cells that cross-react between fungal proteins and their human counterparts. These mechanisms contribute to skin inflammation in atopic dermatitis and therefore influence the course of this disorder. Finally, wediscuss the possible benefit of an anti-Malassezia spp. treatment in patients with atopic dermatitis. DOI: https://doi.org/10.3390/jcm4061217 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-113025 Journal Article Published Version The following work is licensed under a Creative Commons: Attribution 4.0 International (CC BY 4.0) License. Originally published at: Glatz, Martin; Bosshard, Philipp P; Hoetzenecker, Wolfram; Schmid-Grendelmeier, Peter (2015). The role of Malassezia spp.
    [Show full text]
  • Nfletffillfl Sm of Nuelieotfl Dles
    Nfletffillflsm of Nuelieotfl dles ucleotides \f consistof a nitrogenousbase, a | \ pentose and a phosphate. The pentose sugaris D-ribosein ribonucleotidesof RNAwhile in deoxyribonucleotides(deoxynucleotides) of i Aspariaie--'N.,,,t .J . DNA, the sugaris 2-deoxyD-ribose. Nucleotides t participate in almost all the biochemical processes/either directly or indirectly.They are the structuralcomponents of nucleicacids (DNA, Y RNA), coenzymes, and are involved in tne Glutamine regulationof severalmetabolic reactions. Fig. 17.1 : The sources of individuat atoms in purine ring. (Note : Same colours are used in the syntheticpathway Fig. lZ.2). n T. C4, C5 and N7 are contributedby glycine. Many compoundscontribute to the purine ring of the nucleotides(Fig.t7.l). 5. C6 directly comes from COr. 1. purine N1 of is derivedfrom amino group It should be rememberedthat purine bases of aspartate. are not synthesizedas such,but they are formed as ribonucleotides. The purines 2. C2 and Cs arise from formate of N10- are built upon a formyl THF. pre-existing ribose S-phosphate. Liver is the major site for purine nucleotide synthesis. 3. N3 and N9 are obtainedfrom amide group Erythrocytes,polymorphonuclear leukocytes and of glutamine. brain cannot producepurines. 388 BIOCHEMISTF|Y m-gg-o-=_ |l Formylglycinamide ribosyl S-phosphate Kn H) Glutam H \-Y OH +ATt OH OH Glutame cl-D-Ribose-S-phosphate + ADP orr-l t'1 PRPPsYnthetase ,N o"t*'] \cH + Hrcl-itl HN:C-- O EO-qn2-O.- H -NH l./ \l KH H) I u \.]_j^/ r,\-iEl-/^\-td Ribose5-P II Formylglycinamidineribosyl-s-phosphate
    [Show full text]
  • Arginase Specific Activity and Nitrogenous Excretion of Penaeus Japonicus Exposed to Elevated Ambient Ammonia
    MARINE ECOLOGY PROGRESS SERIES Published July 10 Mar Ecol Prog Ser Arginase specific activity and nitrogenous excretion of Penaeus japonicus exposed to elevated ambient ammonia Jiann-Chu Chen*,Jiann-Min Chen Department of Aquaculture. National Taiwan Ocean University. Keelung, Taiwan 20224, Republic of China ABSTRACT: Mass-specific activity of arginase and nitrogenous excretion of Penaeus japonicus Bate (10.3 * 3.7 g) were measured for shrimps exposed to 0.029 (control), 1.007 and 10.054 mg 1-' ammonia- N at 32%, S for 24 h. Arginase specific activity of gill, hepatopancreas and midgut increased directly with ambient ammonia-N, whereas arginase specific activity of muscle was inversely related to ambient ammonia-N. Excretion of total-N (total nitrogen), organic-N and urea-N increased, whereas excretion of ammonia-N, nitrate-N and nitrite-N decreased significantly with an increase of ambient ammonia- N. In the control solution, japonlcus excreted 68.94% ammonia-N, 25.39% organic-N and 2.87% urea-N. For the shrimps exposed to 10 mg 1" ammonia-N, ammonia-N uptake occurred, and t.he con- tribution of organic-N and urea-N excretion increased to 90.57 and 8.78%, respectively, of total-N. High levels of arginase specific activity in the gill, midgut and hepatopancreas suggest that there is an alternative route of nitrogenous waste for P. japonicus under ammonia exposure. KEY WORDS: Penaeus japonicus - Ammonia . Arginase activity . Nitrogenous excretion . Metabolism INTRODUCTION processes. Therefore, accumulation of ammonia and its toxicity are of primary concern. Kuruma shrimp Penaeus japonicus Bate, which is Ammonia has been reported to increase molting fre- distributed in Pacific rim countries, is also found in the quency, reduce growth, and even cause mortality of Mediterranean.
    [Show full text]
  • Generated by SRI International Pathway Tools Version 25.0, Authors S
    Authors: Pallavi Subhraveti Ron Caspi Quang Ong Peter D Karp An online version of this diagram is available at BioCyc.org. Biosynthetic pathways are positioned in the left of the cytoplasm, degradative pathways on the right, and reactions not assigned to any pathway are in the far right of the cytoplasm. Transporters and membrane proteins are shown on the membrane. Ingrid Keseler Periplasmic (where appropriate) and extracellular reactions and proteins may also be shown. Pathways are colored according to their cellular function. Gcf_000725805Cyc: Streptomyces xanthophaeus Cellular Overview Connections between pathways are omitted for legibility.
    [Show full text]
  • Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity
    fnins-14-00620 June 27, 2020 Time: 15:13 # 1 REVIEW published: 24 June 2020 doi: 10.3389/fnins.2020.00620 Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity Ananda Staats Pires1,2, Vanessa X. Tan1, Benjamin Heng1, Gilles J. Guillemin1* and Alexandra Latini2* 1 Neuroinflammation Group, Department of Biomedical Sciences, Centre for Motor Neuron Disease Research, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia, 2 Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil Despite the identification of molecular mechanisms associated with pain persistence, no Edited by: significant therapeutic improvements have been made. Advances in the understanding Marianthi Papakosta, of the molecular mechanisms that induce pain hypersensitivity will allow the Takeda Pharmaceutical Company Limited, United States development of novel, effective, and safe therapies for chronic pain. Various pro- Reviewed by: inflammatory cytokines are known to be increased during chronic pain, leading Wladyslaw-Lason, to sustained inflammation in the peripheral and central nervous systems. The Institute of Pharmacology (PAS), Poland pro-inflammatory environment activates additional metabolic routes, including the Ewa Krystyna kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways, which generate bioactive Szczepanska-Sadowska, soluble metabolites with the potential to modulate neuropathic and inflammatory pain Medical University of Warsaw, Poland sensitivity. Inflammation-induced upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) *Correspondence: Gilles J. Guillemin and guanosine triphosphate cyclohydrolase I (GTPCH), both rate-limiting enzymes [email protected] of KYN and BH4 biosynthesis, respectively, have been identified in experimental Alexandra Latini [email protected] chronic pain models as well in biological samples from patients affected by chronic pain.
    [Show full text]