WorldWideScience

Sample records for metabolite 3-aminobenzanthrone enhance

  1. 3-Nitrobenzanthrone and 3-aminobenzanthrone induce DNA damage and cell signalling in Hepa1c1c7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Landvik, N.E. [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 404 Torshov N-4303 Oslo (Norway); Arlt, V.M.; Nagy, E. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG (United Kingdom); Solhaug, A. [Section for Toxicology, Department of Feed and Food Safety, National Veterinary Institute Pb 750 Sentrum, N-0106 Oslo (Norway); Tekpli, X. [EA SeRAIC, Equipe labellisee Ligue contre le Cancer, IFR 140, Universite de Rennes 1, Rennes (France); Schmeiser, H.H. [Research Group Genetic Alteration in Carcinogenesis, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Refsnes, M. [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 404 Torshov N-4303 Oslo (Norway); Phillips, D.H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG (United Kingdom); Lagadic-Gossmann, D. [EA SeRAIC, Equipe labellisee Ligue contre le Cancer, IFR 140, Universite de Rennes 1, Rennes (France); Holme, J.A., E-mail: jorn.holme@fhi.no [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 404 Torshov N-4303 Oslo (Norway)

    2010-02-03

    3-Nitrobenzanthrone (3-NBA) is a mutagenic and carcinogenic environmental pollutant found in diesel exhaust and urban air pollution. In the present work we have characterised the effects of 3-NBA and its metabolite 3-aminobenzanthrone (3-ABA) on cell death and cytokine release in mouse hepatoma Hepa1c1c7 cells. These effects were related to induced DNA damage and changes in cell signalling pathways. 3-NBA resulted in cell death and caused most DNA damage as judged by the amount of DNA adducts ({sup 32}P-postlabelling assay), single strand (ss)DNA breaks and oxidative DNA lesions (comet assay) detected. An increased phosphorylation of H2AX, chk1, chk2 and partly ATM was observed using flow cytometry and/or Western blotting. Both compounds increased phosphorylation of p53 and MAPKs (ERK, p38 and JNK). However, only 3-NBA caused an accumulation of p53 in the nucleus and a translocation of Bax to the mitochondria. The p53 inhibitor pifithrin-alpha inhibited 3-NBA-induced apoptosis, indicating that cell death was a result of the triggering of DNA signalling pathways. The highest phosphorylation of Akt and degradation of I{kappa}B-{alpha} (suggesting activation of NF-{kappa}B) were also seen after treatment with 3-NBA. In contrast 3-ABA increased IL-6 release, but caused little or no toxicity. Cytokine release was inhibited by PD98059 and curcumin, suggesting that ERK and NF-{kappa}B play a role in this process. In conclusion, 3-NBA seems to have a higher potency to induce DNA damage compatible with its cytotoxic effects, while 3-ABA seems to have a greater effect on the immune system.

  2. 3-Nitrobenzanthrone and 3-aminobenzanthrone induce DNA damage and cell signalling in Hepa1c1c7 cells.

    Science.gov (United States)

    Landvik, N E; Arlt, V M; Nagy, E; Solhaug, A; Tekpli, X; Schmeiser, H H; Refsnes, M; Phillips, D H; Lagadic-Gossmann, D; Holme, J A

    2010-02-03

    3-Nitrobenzanthrone (3-NBA) is a mutagenic and carcinogenic environmental pollutant found in diesel exhaust and urban air pollution. In the present work we have characterised the effects of 3-NBA and its metabolite 3-aminobenzanthrone (3-ABA) on cell death and cytokine release in mouse hepatoma Hepa1c1c7 cells. These effects were related to induced DNA damage and changes in cell signalling pathways. 3-NBA resulted in cell death and caused most DNA damage as judged by the amount of DNA adducts ((32)P-postlabelling assay), single strand (ss)DNA breaks and oxidative DNA lesions (comet assay) detected. An increased phosphorylation of H2AX, chk1, chk2 and partly ATM was observed using flow cytometry and/or Western blotting. Both compounds increased phosphorylation of p53 and MAPKs (ERK, p38 and JNK). However, only 3-NBA caused an accumulation of p53 in the nucleus and a translocation of Bax to the mitochondria. The p53 inhibitor pifithrin-alpha inhibited 3-NBA-induced apoptosis, indicating that cell death was a result of the triggering of DNA signalling pathways. The highest phosphorylation of Akt and degradation of IkappaB-alpha (suggesting activation of NF-kappaB) were also seen after treatment with 3-NBA. In contrast 3-ABA increased IL-6 release, but caused little or no toxicity. Cytokine release was inhibited by PD98059 and curcumin, suggesting that ERK and NF-kappaB play a role in this process. In conclusion, 3-NBA seems to have a higher potency to induce DNA damage compatible with its cytotoxic effects, while 3-ABA seems to have a greater effect on the immune system. Copyright 2009 Elsevier B.V. All rights reserved.

  3. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  4. Genotoxicity of 3-nitrobenzanthrone and 3-aminobenzanthrone in MutaMouse and lung epithelial cells derived from MutaMouse.

    Science.gov (United States)

    Arlt, Volker M; Gingerich, John; Schmeiser, Heinz H; Phillips, David H; Douglas, George R; White, Paul A

    2008-11-01

    FE1 lung epithelial cells derived from MutaMouse are a new model system to provide in vitro mutagenicity data with the potential to predict the outcome of an in vivo MutaMouse test. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and urban air pollution. We investigated the mutagenicity and DNA binding of 3-NBA and its main metabolite 3-aminobenzanthrone (3-ABA) in vitro and in vivo in the MutaMouse assay. Mice were treated with 3-NBA or 3-ABA (0, 2 or 5 mg/kg body weight/day) by gavage for 28 days and 28 days later lacZ mutant frequency (MF) was determined in liver, lung and bone marrow. For both compounds, dose-related increases in MF were seen in liver and bone marrow, but not in lung; mutagenic activity was approximately 2-fold lower for 3-ABA than for 3-NBA. With 3-NBA, highest DNA adduct levels (measured by (32)P-post-labelling) were found in liver (approximately 230 adducts per 10(8) nucleotides) with levels 20- to 40-fold lower in bone marrow and lung. With 3-ABA, DNA adduct levels were again highest in the liver, but approximately 4-fold lower than for 3-NBA. FE1 cells were exposed to up to 10 microg/ml 3-NBA or 3-ABA for 6 h with or without exogenous activation (S9) and harvested after 3 days. For 3-NBA, there was a dose-related increase in MF both with and without S9 mix, which was >10 times higher than observed in vivo. At the highest concentration of 3-ABA (10 microg/ml), we found only around a 2-fold increase in MF relative to controls. DNA adduct formation in FE1 cells was dose-dependent for both compounds, but 10- to 20-fold higher for 3-NBA compared to 3-ABA. Collectively, our data indicate that MutaMouse FE1 cells are well suited for cost-effective testing of suspected mutagens with different metabolic activation pathways as a guide for subsequent in vivo MutaMouse testing.

  5. Base-Displaced Intercalated Structure of the N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone DNA Adduct.

    Science.gov (United States)

    Politica, Dustin A; Malik, Chanchal K; Basu, Ashis K; Stone, Michael P

    2015-12-21

    3-Nitrobenzanthrone (3-NBA), an environmental mutagen found in diesel exhaust and a suspected carcinogen, undergoes metabolic reduction followed by reaction with DNA to form aminobenzanthrone (ABA) adducts, with the major alkylation product being N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (C8-dG-ABA). Site-specific synthesis of the C8-dG-ABA adduct in the oligodeoxynucleotide 5'-d(GTGCXTGTTTGT)-3':5'-d(ACAAACACGCAC)-3'; X = C8-dG-ABA adduct, including codons 272-275 of the p53 gene, has allowed for investigation into the structural and thermodynamic properties of this adduct. The conformation of the C8-dG-ABA adduct was determined using NMR spectroscopy and was refined using molecular dynamics (MD) calculations restrained by experimentally determined interproton distance restraints obtained from NOE experiments. The refined structure revealed that the C8-dG-ABA adduct formed a base-displaced intercalated conformation. The adducted guanine was shifted into the syn conformation about the glycosidic bond. The 5'- and 3'-neighboring base pairs remained intact. While this facilitated π-stacking interactions between the ABA moiety and neighboring bases, the thermal melting temperature (Tm) of the adduct-containing duplex showed a decrease of 11 °C as compared to the corresponding unmodified oligodeoxynucleotide duplex. Overall, in this sequence, the base-displaced intercalated conformation of the C8-dG-ABA lesion bears similarity to structures of other arylamine C8-dG adducts. However, in this sequence, the base-displaced intercalated conformation for the C8-dG-ABA adduct differs from the conformation of the N(2)-dG-ABA adduct reported by de los Santos and co-workers, in which it is oriented in the minor groove toward the 5' end of the duplex, with the modified guanine remaining in the anti conformation about the glyosidic torsion angle, and the complementary base remaining within the duplex. The results are discussed in relationship to differences between the C8-d

  6. Base-Displaced Intercalated Structure of the N-(2′-Deoxyguanosin-8-yl)-3-aminobenzanthrone DNA Adduct

    Science.gov (United States)

    Politica, Dustin A.; Malik, Chanchal K.; Basu, Ashis K.; Stone, Michael P.

    2016-01-01

    3-Nitrobenzanthrone (3-NBA), an environmental mutagen found in diesel exhaust and a suspected carcinogen, undergoes metabolic reduction followed by reaction with DNA to form aminobenzanthrone (ABA) adducts, with the major alkylation product being N-(2′-deoxyguanosin-8-yl)-3-aminobenzanthrone (C8-dG-ABA). Site-specific synthesis of the C8-dG-ABA adduct in the oligodeoxynucleotide 5'-d(GTGCXTGTTTGT)-3':5'-d(ACAAACACGCAC)-3'; X = C8-dG-ABA adduct, including codons 272-275 of the p53 gene, has allowed for investigation into the structural and thermodynamic properties of this adduct. The conformation of the C8-dG-ABA adduct was determined using NMR spectroscopy and was refined using molecular dynamics (MD) calculations restrained by experimentally determined interproton distance restraints obtained from NOE experiments. The refined structure revealed that the C8-dG-ABA adduct formed a base-displaced intercalated conformation. The adducted guanine was shifted into the syn conformation about the glycosidic bond. The 5'- and 3'-neighboring base pairs remained intact. While this facilitated π-stacking interactions between the ABA moiety and neighboring bases, the thermal melting temperature (Tm) of the adduct-containing duplex showed a decrease of 11 °C as compared to the corresponding unmodified oligodeoxynucleotide duplex. Overall, in this sequence, the base-displaced intercalated conformation of the C8-dG-ABA lesion bears similarity to structures of other arylamine C8-dG adducts. However, in this sequence, the base-displaced intercalated conformation for the C8-dG-ABA adduct differs from the conformation of the N2-dG-ABA adduct reported by de los Santos and co-workers, which oriented in the minor groove towards the 5' end of the duplex, with the modified guanine remaining in the anti conformation about the glyosidic torsion angle, and the complementary base remaining within the duplex. The results are discussed in relationship to differences between the C8-dG-ABA and

  7. S-(3-Aminobenzanthron-2-yl)cysteine in the globin of rats as a novel type of adduct and possible biomarker of exposure to 3-nitrobenzanthrone, a potent environmental carcinogen.

    Science.gov (United States)

    Linhart, Igor; Hanzlíková, Iveta; Mráz, Jaroslav; Dušková, Šárka

    2017-10-01

    3-Nitrobenzanthrone (3-NBA), a potent environmental mutagen and carcinogen, is known to be activated in vivo to 3-benzanthronylnitrenium ion which forms both NH and C2-bound adducts with DNA and also reacts with glutathione giving rise to urinary 3-aminobenzanthron-2-ylmercapturic acid. In this study, acid hydrolysate of globin from rats dosed intraperitoneally with 3-NBA was analysed by HPLC/MS to identify a novel type of cysteine adduct, 3-aminobenzanthron-2-ylcysteine (3-ABA-Cys), confirmed using a synthesised standard. The 3-ABA-Cys levels in globin peaked after single 3-NBA doses of 1 and 2 mg/kg on day 2 to attain 0.25 and 0.49 nmol/g globin, respectively, thereafter declining slowly to 70-80% of their maximum values during 15 days. After dosing rats for three consecutive days with 1 mg 3-NBA/kg a significant cumulation of 3-ABA-Cys in globin was observed. 3-ABA-Cys was also found in the plasma hydrolysate. Herein, after dosing with 1 and 2 mg 3-NBA/kg the adduct levels peaked on day 1 at 0.15 and 0.51 nmol/ml plasma, respectively, thereafter declining rapidly to undetectable levels on day 15. In addition, sulphinamide adducts were also found in the exposed rats, measured indirectly as 3-aminobenzanthrone (3-ABA) split off from globin by mild acid hydrolysis. Levels of both types of adducts in the globin samples parallelled very well with 3-ABA/3-ABA-Cys ratio being around 1:8. In conclusion, 3-ABA-Cys is the first example of arylnitrenium-cysteine adduct in globin representing a new promising class of biomarkers to assess cumulative exposures to aromatic amines, nitroaromatics and heteroaromatic amines.

  8. DNA adduct formation by the ubiquitous environmental pollutant 3-nitrobenzanthrone and its metabolites in rats

    International Nuclear Information System (INIS)

    Arlt, Volker M.; Sorg, Bernd L.; Osborne, Martin; Hewer, Alan; Seidel, Albrecht; Schmeiser, Heinz H.; Phillips, David H.

    2003-01-01

    Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro. 3-Aminobenzanthrone (3-ABA), 3-acetylaminobenzanthrone (3-Ac-ABA), and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) were identified as 3-NBA metabolites. In order to gain insight into the pathways of metabolic activation leading to 3-NBA-derived DNA adducts we treated Wistar rats intraperitoneally with 2 mg/kg body weight of 3-NBA, 3-ABA, 3-Ac-ABA, or N-Ac-N-OH-ABA and compared DNA adducts present in different organs. With each compound either four or five DNA adduct spots were detected by TLC in all tissues examined (lung, liver, kidney, heart, pancreas, and colon) using the nuclease P1 or butanol enrichment version of the 32 P-postlabelling method, respectively. Using HPLC co-chromatographic analysis we showed that all major 3-NBA-DNA adducts produced in vivo in rats are derived from reductive metabolites bound to purine bases and lack an N-acetyl group. Our results indicate that 3-NBA metabolites (3-ABA, 3-Ac-ABA and N-Ac-N-OH-ABA) undergo several biotransformations and that N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be the common intermediate in 3-NBA-derived DNA adduct formation. Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation

  9. Simple Method for Enhanced Production of Secondary Metabolites ...

    African Journals Online (AJOL)

    iict

    2013-04-10

    Apr 10, 2013 ... Callus cultures of Charybdis congesta were initiated in vitro and the effect of growth regulators was tested on callus growth and secondary metabolite production. Among several standard media formulated for use in the present study, MS and B5 were found to be potentially active and facilitated.

  10. Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

    Science.gov (United States)

    Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

    2015-01-25

    Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

  11. Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

    OpenAIRE

    Pfister, Sandra L.

    2011-01-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

  12. Gamma irradiation of medicinally important plants and the enhancement of secondary metabolite production.

    Science.gov (United States)

    Vardhan, P Vivek; Shukla, Lata I

    2017-09-01

    metabolites in response to various biotic and abiotic stresses is compared with ionizing radiation. A ∼5- to 20-fold increase is noted with ∼20 Gy irradiation dose. It increases the yield of secondary metabolites by enhancing the activity of certain key biosynthetic enzymes. Identification of the optimum dose is the important step in the large-scale production of secondary metabolites at industrial level.

  13. Tilting Plant Metabolism for Improved Metabolite Biosynthesis and Enhanced Human Benefit

    Directory of Open Access Journals (Sweden)

    Bhekumthetho Ncube

    2015-07-01

    Full Text Available The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this biogenic pool of phytochemicals for products such as pharmaceuticals, fragrances, dyes, and insecticides, among others. With consumers showing increasing interests in these products, innovative biotechnological techniques are being developed and employed to alter plant secondary metabolism in efforts to improve on the quality and quantity of specific metabolites of interest. This review provides an overview of the biosynthesis for phytochemical compounds with medicinal and other related properties and their associated biological activities. It also provides an insight into how their biosynthesis/biosynthetic pathways have been modified/altered to enhance production.

  14. Metabolite cross-feeding enhances virulence in a model polymicrobial infection.

    Directory of Open Access Journals (Sweden)

    Matthew M Ramsey

    2011-03-01

    Full Text Available Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities.

  15. The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity.

    Science.gov (United States)

    Stiborová, Marie; Dracínská, Helena; Mizerovská, Jana; Frei, Eva; Schmeiser, Heinz H; Hudecek, Jirí; Hodek, Petr; Phillips, David H; Arlt, Volker M

    2008-05-02

    3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air pollution. Using the (32)P-postlabelling method, we found that 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical five DNA adducts. We have demonstrated the importance of pulmonary and renal NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP) 1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When cytosols from rats treated i.p. with 40mg/kg bw of 3-NBA were incubated with 3-NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. Incubations of 3-ABA with microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct formation relative to controls. The stimulation of DNA adduct formation correlated with the potential of 3-NBA to induce protein expression and activity of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential.

  16. Time resolved and label free monitoring of extracellular metabolites by surface enhanced Raman spectroscopy.

    Directory of Open Access Journals (Sweden)

    Victoria Shalabaeva

    Full Text Available Metabolomics is an emerging field of cell biology that aims at the comprehensive identification of metabolite levels in biological fluids or cells in a specific functional state. Currently, the major tools for determining metabolite concentrations are mass spectrometry coupled with chromatographic techniques and nuclear magnetic resonance, which are expensive, time consuming and destructive for the samples. Here, we report a time resolved approach to monitor metabolite dynamics in cell cultures, based on Surface Enhanced Raman Scattering (SERS. This method is label-free, easy to use and provides the opportunity to simultaneously study a broad range of molecules, without the need to process the biological samples. As proof of concept, NIH/3T3 cells were cultured in vitro, and the extracellular medium was collected at different time points to be analyzed with our engineered SERS substrates. By identifying individual peaks of the Raman spectra, we showed the simultaneous detection of several components of the conditioned medium, such as L-tyrosine, L-tryptophan, glycine, L-phenylalanine, L-histidine and fetal bovine serum proteins, as well as their intensity changes during time. Furthermore, analyzing the whole Raman data set with the Principal Component Analysis (PCA, we demonstrated that the Raman spectra collected at different days of culture and clustered by similarity, described a well-defined trajectory in the principal component plot. This approach was then utilized to determine indirectly the functional state of the macrophage cell line Raw 264.7, stimulated with the lipopolysaccharide (LPS for 24 hours. The collected spectra at different time points, clustered by the PCA analysis, followed a well-defined trajectory, corresponding to the functional change of cells toward the activated pro-inflammatory state induced by the LPS. This study suggests that our engineered SERS surfaces can be used as a versatile tool both for the characterization

  17. Metabolite Profiling of Wheat Seedlings Induced by Chitosan: Revelation of the Enhanced Carbon and Nitrogen Metabolism

    Directory of Open Access Journals (Sweden)

    Xiaoqian Zhang

    2017-11-01

    Full Text Available Chitosan plays an important role in regulating growth and eliciting defense in many plant species. However, the exact metabolic response of plants to chitosan is still not clear. The present study performed an integrative analysis of metabolite profiles in chitosan-treated wheat seedlings and further investigated the response of enzyme activities and transcript expression related to the primary carbon (C and nitrogen (N metabolism. Metabolite profiling revealed that chitosan could induce significant difference of organic acids, sugars and amino acids in leaves of wheat seedlings. A higher accumulation of sucrose content was observed after chitosan treatment, accompanied by an increase in sucrose phosphate synthase (SPS and fructose 1, 6-2 phosphatase (FBPase activities as well as an up-regulation of relative expression level. Several metabolites associated with tricarboxylic acid (TCA cycle, including oxaloacetate and malate, were also improved along with an elevation of phosphoenolpyruvate carboxylase (PEPC and pyruvate dehydrogenase (PDH activities. On the other hand, chitosan could also enhance the N reduction and N assimilation. Glutamate, aspartate and some other amino acids were higher in chitosan-treated plants, accompanied by the activation of key enzymes of N reduction and glutamine synthetase/glutamate synthase (GS/GOGAT cycle. Together, these results suggested a pleiotropic modulation of carbon and nitrogen metabolism in wheat seedlings induced by chitosan and provided a significant insight into the metabolic mechanism of plants in response to chitosan for the first time, and it would give a basic guidance for the future application of chitosan in agriculture.

  18. Enhancement of Leaf Gas Exchange and Primary Metabolites under Carbon Dioxide Enrichment Up-Regulates the Production of Secondary Metabolites in Labisia pumila Seedlings

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2011-05-01

    Full Text Available A split plot 3 by 3 experiment was designed to investigate and distinguish the relationships among production of primary metabolites (soluble sugar and starch, secondary metabolites (total phenolics, TP; total flavonoids, TF and leaf gas exchange of three varieties of the Malaysian medicinal herb Labisia pumila Blume, namely the varieties alata, pumila and lanceolata, under three levels of CO2 enrichment (400, 800 and 1,200 µmol mol−1 for 15 weeks. The treatment effects were solely contributed by CO2 enrichment levels; no varietal differences were observed. As CO2 levels increased from 400 to 1,200 µmol mol−1, the production of carbohydrates also increased steadily, especially for starch more than soluble sugar (sucrose. TF and TP content, simultaneously, reached their peaks under 1,200 µmol exposure, followed by 800 and 400 µmol mol−1. Net photosynthesis (A and quantum efficiency of photosystem II (fv/fm were also enhanced as CO2 increased from 400 to 1,200 µmol mol−1. Leaf gas exchange characteristics displayed a significant positive relationship with the production of secondary metabolites and carbohydrate contents. The increase in production of TP and TFs were manifested by high C/N ratio and low protein content in L. pumila seedlings, and accompanied by reduction in cholorophyll content that exhibited very significant negative relationships with total soluble sugar, starch and total non structural carbohydrate.

  19. Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

    Science.gov (United States)

    Dankel, Scott J; Mattocks, Kevin T; Jessee, Matthew B; Buckner, Samuel L; Mouser, J Grant; Loenneke, Jeremy P

    2017-11-01

    Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.

  20. Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.

    Science.gov (United States)

    Pfister, Sandra L

    2011-04-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.

  1. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Yao Pan

    2015-08-01

    Full Text Available Trichloroethylene (TCE is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA and dichloroacetic acid (DCA, on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  2. Binary culture of microalgae as an integrated approach for enhanced biomass and metabolites productivity, wastewater treatment, and bioflocculation.

    Science.gov (United States)

    Rashid, Naim; Park, Won-Kun; Selvaratnam, Thinesh

    2018-03-01

    Ecological studies of microalgae have revealed their potential to co-exist in the natural environment. It provides an evidence of the symbiotic relationship of microalgae with other microorganisms. The symbiosis potential of microalgae is inherited with distinct advantages, providing a venue for their scale-up applications. The deployment of large-scale microalgae applications is limited due to the technical challenges such as slow growth rate, low metabolites yield, and high risk of biomass contamination by unwanted bacteria. However, these challenges can be overcome by exploring symbiotic potential of microalgae. In a symbiotic system, photosynthetic microalgae co-exist with bacteria, fungi, as well as heterotrophic microalgae. In this consortium, they can exchange nutrients and metabolites, transfer gene, and interact with each other through complex metabolic mechanism. Microalgae in this system, termed as a binary culture, are reported to exhibit high growth rate, enhanced bio-flocculation, and biochemical productivity without experiencing contamination. Binary culture also offers interesting applications in other biotechnological processes including bioremediation, wastewater treatment, and production of high-value metabolites. The focus of the study is to provide a perspective to enhance the understanding about microalgae binary culture. In this review, the mechanism of binary culture, its potential, and limitations are briefly discussed. A number of queries are evolved through this study, which needs to be answered by executing future research to assess the real potential of binary culture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Automatic untargeted metabolic profiling analysis coupled with Chemometrics for improving metabolite identification quality to enhance geographical origin discrimination capability.

    Science.gov (United States)

    Han, Lu; Zhang, Yue-Ming; Song, Jing-Jing; Fan, Mei-Juan; Yu, Yong-Jie; Liu, Ping-Ping; Zheng, Qing-Xia; Chen, Qian-Si; Bai, Chang-Cai; Sun, Tao; She, Yuan-Bin

    2018-03-16

    Untargeted metabolic profiling analysis is employed to screen metabolites for specific purposes, such as geographical origin discrimination. However, the data analysis remains a challenging task. In this work, a new automatic untargeted metabolic profiling analysis coupled with a chemometric strategy was developed to improve the metabolite identification results and to enhance the geographical origin discrimination capability. Automatic untargeted metabolic profiling analysis with chemometrics (AuMPAC) was used to screen the total ion chromatographic (TIC) peaks that showed significant differences among the various geographical regions. Then, a chemometric peak resolution strategy is employed for the screened TIC peaks. The retrieved components were further analyzed using ANOVA, and those that showed significant differences were used to build a geographical origin discrimination model by using two-way encoding partial least squares. To demonstrate its performance, a geographical origin discrimination of flaxseed samples from six geographical regions in China was conducted, and 18 TIC peaks were screened. A total of 19 significant different metabolites were obtained after the peak resolution. The accuracy of the geographical origin discrimination was up to 98%. A comparison of the AuMPAC, AMDIS, and XCMS indicated that AuMPACobtained the best geographical origin discrimination results. In conclusion, AuMPAC provided another method for data analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Phosphate enhances uptake of As species in garland chrysanthemum (C. coronarium) applied with chicken manure bearing roxarsone and its metabolites.

    Science.gov (United States)

    Yao, Lixian; Huang, Lianxi; He, Zhaohuan; Zhou, Changming; Li, Guoliang; Deng, Xiancai

    2015-03-01

    Roxarsone (ROX), a world widely used feed organoarsenic additive in animal production, can be excreted as itself and its metabolites in animal manure. Animal manure is commonly land applied with phosphorous (P) fertilizer to enhance the P phytoavailability in agriculture. We investigated the accumulation of As species in garland chrysanthemum (C. coronarium) plants fertilized with 1% (w/w, manure/soil) chicken manure bearing ROX and its metabolites, plus 0, 0.05, 0.1, 0.2, 0.4, and 0.8 g P2O5/kg, respectively. The results show that As(III) was the sole As compound in garland chrysanthemum shoots, and As(III) and As(V) were detectable in roots. Elevated phosphate level supplied more As(V) for garland chrysanthemum roots through competitive desorption in rhizosphere, leading to significantly enhanced accumulation of As species in plants. As(III) was the predominant As form in plants (85.0∼90.6%). Phosphate could not change the allocation of As species in plants. Hence, the traditional practice that animal manure is applied with P fertilizer may inadvertently increase the potential risk of As contamination in crop via the way ROX → animal → animal manure → soil → crop.

  5. 1D Simulations for Microbial Enhanced Oil Recovery with Metabolite Partitioning

    DEFF Research Database (Denmark)

    Nielsen, Sidsel Marie; Shapiro, Alexander; Michelsen, Michael Locht

    2010-01-01

    in the water phase is reduced. The metabolite produced is surfactant reducing oil–water interfacial tension, which results in oil mobilization. The reduction of interfacial tension is implemented through relative permeability curve modifications primarily by lowering residual oil saturation....... The characteristics for the water phase saturation profiles and the oil recovery curves are elucidated. However, the effect from the surfactant is not necessarily restricted to influence only interfacial tension, but it can also be an approach for changing, e.g., wettability. The distribution coefficient determines...... the time lag, until residual oil mobilization is initialized. It has also been found that the final recovery depends on the distance from the inlet before the surfactant effect takes place. The surfactant effect position is sensitive to changes in maximum growth rate, and injection concentrations...

  6. ATNT: an enhanced system for expression of polycistronic secondary metabolite gene clusters in Aspergillus niger.

    Science.gov (United States)

    Geib, Elena; Brock, Matthias

    2017-01-01

    Fungi are treasure chests for yet unexplored natural products. However, exploitation of their real potential remains difficult as a significant proportion of biosynthetic gene clusters appears silent under standard laboratory conditions. Therefore, elucidation of novel products requires gene activation or heterologous expression. For heterologous gene expression, we previously developed an expression platform in Aspergillus niger that is based on the transcriptional regulator TerR and its target promoter P terA . In this study, we extended this system by regulating expression of terR  by the doxycycline inducible Tet-on system. Reporter genes cloned under the control of the target promoter P terA remained silent in the absence of doxycycline, but were strongly expressed when doxycycline was added. Reporter quantification revealed that the coupled system results in about five times higher expression rates compared to gene expression under direct control of the Tet-on system. As production of secondary metabolites generally requires the expression of several biosynthetic genes, the suitability of the self-cleaving viral peptide sequence P2A was tested in this optimised expression system. P2A allowed polycistronic expression of genes required for Asp-melanin formation in combination with the gene coding for the red fluorescent protein tdTomato. Gene expression and Asp-melanin formation was prevented in the absence of doxycycline and strongly induced by addition of doxycycline. Fluorescence studies confirmed the correct subcellular localisation of the respective enzymes. This tightly regulated but strongly inducible expression system enables high level production of secondary metabolites most likely even those with toxic potential. Furthermore, this system is compatible with polycistronic gene expression and, thus, suitable for the discovery of novel natural products.

  7. Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats.

    Science.gov (United States)

    Atkin, I; Dean, D D; Muniz, O E; Agundez, A; Castiglione, G; Cohen, G; Howell, D S; Ornoy, A

    1992-08-01

    Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform-methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D-deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive

  8. Simultaneous multiplexed quantification of caffeine and its major metabolites theobromine and paraxanthine using surface-enhanced Raman scattering.

    Science.gov (United States)

    Alharbi, Omar; Xu, Yun; Goodacre, Royston

    2015-11-01

    Accurate quantitative measurement of drugs and their metabolites is important as this can be used to establish long-term abuse of illicit materials as well as establish accurate drug dosing for legal therapeutics. However, the levels of drugs and xenometabolites found in human body fluids necessitate methods that are highly sensitive as well as reproducible with the potential for portability. Raman spectroscopy does offer excellent reproducibility, portability and chemical specificity, but unfortunately, the Raman effect is generally too weak unless it is enhanced. We therefore developed surface-enhanced Raman scattering (SERS) and combined it with the powerful machine learning technique of artificial neural networks to enable rapid quantification of caffeine and its two major metabolites theobromine and paraxanthine. We established a three-way mixture analysis from 10(-5) to 10(-7) mol/dm(3), and excellent predictions were generated for all three analytes in tertiary mixtures. The range we selected reflects the levels found in human body fluids, and the typical errors for our portable SERS analysis were 1.7 × 10(-6) mol/dm(3) for caffeine, 8.8 × 10(-7) mol/dm(3) for theobromine and 9.6 × 10(-7) mol/dm(3) for paraxanthine. We believe this demonstrates the exciting prospect of using SERS for the quantitative analysis of multiple analytes simultaneously without recourse to lengthy and time-consuming chromatography, a method that often has to be combined with mass spectrometry.

  9. Plant Secondary Metabolites in some Medicinal Plants of Mongolia Used for Enhancing Animal Health and Production

    Directory of Open Access Journals (Sweden)

    Makkar, HPS.

    2009-01-01

    Full Text Available The levels and activities of a number of plant secondary metabolites (PSMs are known to increase in response to increase in stress. The Mongolian plants considered to possess medicinal properties may contain novel compounds since they are exposed to severe conditions; such plants could become good candidates for modern drug discovery programmes. Information on distribution, palatability to livestock and opinion of local people on their nutritive and medicinal values was compiled for 15 plant materials from 14 plant species considered important for medicinal purposes. These plants were evaluated for nutritive value and PSMs: tannins, saponins, lectins, alkaloids and cyanogens. High levels of tannins were found in roots of Bergenia crassifolia and in leaves of B. crassifolia, Vaccinium vitisidaea and Rheum undulatum. High lectin activity (haemagglutination was present in B. crassifolia roots, and leaves of R. undulatum, Iris lacteal and Thymus gobicus contained weak lectin activity. Tanacetum vulgare, Serratula centauroids, Taraxacum officinale and Delphinum elatum leaves contained saponin activity (haemolysis. Alkaloids and cyanogens were not present in any of the samples. The paper discusses the known medicinal uses of these plants in light of the PSMs levels, and identifies plant samples for future applications in human and livestock health, welfare and safety.

  10. Enhancement of Calibrachoa growth, secondary metabolites and bioactivity using seaweed extracts.

    Science.gov (United States)

    Elansary, Hosam O; Norrie, Jeff; Ali, Hayssam M; Salem, Mohamed Z M; Mahmoud, Eman A; Yessoufou, Kowiyou

    2016-09-02

    Calibrachoa x hybrida (Solanaceae) cultivars are widely used in North and South America as ornamental plants. Their potential as a source of antimicrobial compounds might be enhanced by seaweed extract (SWE) applications. SWE of Ascophyllum nodosum were applied at 5 and 7 ml/L as a soil drench or foliar spray on Calibrachoa cultivars of Superbells® 'Dreamsicle' (CHSD) and Superbells® 'Frost Fire' (CHSF). The total phenolics, tannins and antioxidants composition as well as specific flavonols in leaf extracts were determined. Further, the chemical composition of SWE was assessed. The drench and foliar SWE treatments significantly enhanced Calibrachoa cultivars leaf number and area, dry weight, plant height, antioxidant capacity as well as phenolic, flavonols and tannin content. The increased growth and composition of phenols, flavonols and tannins was attributed to the stimulatory effects of SWE mineral composition. The antifungal activity of Calibrachoa cultivars was significantly enhanced following SWE treatments and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were in the range of 0.07-0.31 mg/ml and from 0.16 to 0.56 mg/ml, respectively. Moreover, antibacterial activity was significantly increased and the MIC and minimum bactericidal concentration (MBC) measurements were in the range of 0.06-0.23 mg/ml and from 0.10 to 0.44 mg/ml, respectively. The most sensitive fungus to SWE treatments was C. albicans and the most sensitive bacterium was E. cloacae. The results suggest that enhanced antifungal and antibacterial activities might be attributed to significant increases of phenolic, flavonols and tannin contents, which ultimately enhance the potential of Calibrachoa as a natural source of alternative antibiotics.

  11. Modafinil and its metabolites enhance the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

    Science.gov (United States)

    Zolkowska, Dorota; Andres-Mach, Marta; Prisinzano, Thomas E; Baumann, Michael H; Luszczki, Jarogniew J

    2015-07-01

    Seizures occur when the excitability of brain circuits is not sufficiently restrained by inhibitory mechanisms. Although modafinil is reported to reduce GABA-activated currents and extracellular GABA levels in the brain, the drug exerts anticonvulsant effects in animal studies. The aim of this study was to determine the effects of modafinil and its metabolites (sulfone and carboxylic acid) on the anticonvulsant action of four classical antiepileptic drugs (AEDs)-carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA). Anticonvulsant activity was assessed with the maximal electroshock seizure threshold (MEST) test and MES test in mice. Brain concentrations of AEDs were measured to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Intraperitoneal injection of 75 mg kg(-1) of modafinil or its metabolites significantly elevated the threshold for electroconvulsions in mice, whereas 50 mg kg(-1) of each compound enhanced the anticonvulsant activity of CBZ, PHT, and VPA, but not that of PB. A 25-mg kg(-1) dose of modafinil or its sulfone metabolite enhanced anticonvulsant activity of VPA. Modafinil and its metabolites (50 mg kg(-1)) did not alter total brain concentrations of PB and VPA but did elevate CBZ and PHT. Enhancement of anticonvulsant actions of VPA by modafinil in the mouse MES model is a pharmacodynamic effect. Collectively, our data suggest that modafinil may be a safe and beneficial adjunct to the therapeutic effects of AEDs in human patients.

  12. A bell pepper cultivar tolerant to chilling enhanced nitrogen allocation and stress-related metabolite accumulation in the roots in response to low root-zone temperature.

    Science.gov (United States)

    Aidoo, Moses Kwame; Sherman, Tal; Lazarovitch, Naftali; Fait, Aaron; Rachmilevitch, Shimon

    2017-10-01

    Two bell pepper (Capsicum annuum) cultivars, differing in their response to chilling, were exposed to three levels of root-zone temperatures. Gas exchange, shoot and root phenology, and the pattern of change of the central metabolites and secondary metabolites caffeate and benzoate in the leaves and roots were profiled. Low root-zone temperature significantly inhibited gaseous exchange, with a greater effect on the sensitive commercial pepper hybrid (Canon) than on the new hybrid bred to enhance abiotic stress tolerance (S103). The latter was less affected by the treatment with respect to plant height, shoot dry mass, root maximum length, root projected area, number of root tips and root dry mass. More carbon was allocated to the leaves of S103 than nitrogen at 17°C, while in the roots at 17°C, more nitrogen was allocated and the ratio between C/N decreased. Metabolite profiling showed greater increase in the root than in the leaves. Leaf response between the two cultivars differed significantly. The roots accumulated stress-related metabolites including γ-aminobutyric acid (GABA), proline, galactinol and raffinose and at chilling (7°C) resulted in an increase of sugars in both cultivars. Our results suggest that the enhanced tolerance of S103 to root cold stress, reflected in the relative maintenance of shoot and root growth, is likely linked to a more effective regulation of photosynthesis facilitated by the induction of stress-related metabolism. © 2017 Scandinavian Plant Physiology Society.

  13. Enhancement of gama-aminobutyric acid (GABA) and other health-related metabolites in germinated red rice (Oryza sativa L.) by ultrasonication.

    Science.gov (United States)

    Ding, Junzhou; Ulanov, Alexander V; Dong, Mengyi; Yang, Tewu; Nemzer, Boris V; Xiong, Shanbai; Zhao, Siming; Feng, Hao

    2018-01-01

    Red rice (Oryza sativa L.) that has a red (reddish brown) bran layer in de-hulled rice is known to contain rich biofunctional components. Germination is an effective technique to improve the nutritional quality, digestibility, and flavor of de-hulled rice. Ultrasonication, a form of physical stimulation, has been documented as a novel approach to improve the nutritional quality of plant-based food. This study was undertaken to test the use of ultrasound to enhance the nutritional value of red rice. Ultrasonication (5min, 16W/L) was applied to rice during soaking or after 66h germination. Changes of metabolites (amino acids, sugars, and organic acids) in red rice treated by ultrasonication were determined using a GC/MS plant primary metabolomics analysis platform. Differential expressed metabolites were identified through multivariate statistical analysis. Results showed that γ-aminobutyric acid (GABA) and riboflavin (vitamin B 2 ) in red rice significantly increased after germination for 72h, and then experienced a further increase after treatment by ultrasound at different stages during germination. The metabolomics analysis showed that some plant metabolites, i.e. GABA, O-phosphoethanolamine, and glucose-6-phosphate were significantly increased after the ultrasonic treatment (VIP>1.5) in comparison with the untreated germinated rice. The findings of this study showed that controlled germination with ultrasonic stress is an effective method to enhance GABA and other health-promoted components in de-hulled rice. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Chemical Elicitor-Induced Modulation of Antioxidant Metabolism and Enhancement of Secondary Metabolite Accumulation in Cell Suspension Cultures of Scrophularia kakudensis Franch

    Directory of Open Access Journals (Sweden)

    Abinaya Manivannan

    2016-03-01

    Full Text Available Scrophularia kakudensis is an important medicinal plant with pharmaceutically valuable secondary metabolites. To develop a sustainable source of naturaceuticals with vital therapeutic importance, a cell suspension culture was established in S. kakudensis for the first time. Friable calli were induced from the leaf explants cultured on a Murashige and Skoog (MS medium containing 3.0 mg·L−1 6-benzyladenine (BA in a combination with 2 mg·L−1 2,4-dichlorophenoxy acetic acid (2,4-D. From the callus cultures, a cell suspension culture was initiated and the cellular differentiation was investigated. In addition, the effect of biotic elicitors such as methyl jasmonate (MeJa, salicylic acid (SA, and sodium nitroprusside (SNP on the accumulation of secondary metabolites and antioxidant properties was demonstrated. Among the elicitors, the MeJa elicited the accumulation of total phenols, flavonoids, and acacetin, a flavonoid compound with multiple pharmaceutical values. Similarly, the higher concentrations of the MeJa significantly modulated the activities of antioxidant enzymes and enhanced the scavenging potentials of free radicals of cell suspension extracts. Overall, the outcomes of this study can be utilized for the large scale production of pharmaceutically important secondary metabolites from S. kakudensis through cell suspension cultures.

  15. Chemical Elicitor-Induced Modulation of Antioxidant Metabolism and Enhancement of Secondary Metabolite Accumulation in Cell Suspension Cultures of Scrophularia kakudensis Franch.

    Science.gov (United States)

    Manivannan, Abinaya; Soundararajan, Prabhakaran; Park, Yoo Gyeong; Jeong, Byoung Ryong

    2016-03-18

    Scrophularia kakudensis is an important medicinal plant with pharmaceutically valuable secondary metabolites. To develop a sustainable source of naturaceuticals with vital therapeutic importance, a cell suspension culture was established in S. kakudensis for the first time. Friable calli were induced from the leaf explants cultured on a Murashige and Skoog (MS) medium containing 3.0 mg·L(-1) 6-benzyladenine (BA) in a combination with 2 mg·L(-1) 2,4-dichlorophenoxy acetic acid (2,4-D). From the callus cultures, a cell suspension culture was initiated and the cellular differentiation was investigated. In addition, the effect of biotic elicitors such as methyl jasmonate (MeJa), salicylic acid (SA), and sodium nitroprusside (SNP) on the accumulation of secondary metabolites and antioxidant properties was demonstrated. Among the elicitors, the MeJa elicited the accumulation of total phenols, flavonoids, and acacetin, a flavonoid compound with multiple pharmaceutical values. Similarly, the higher concentrations of the MeJa significantly modulated the activities of antioxidant enzymes and enhanced the scavenging potentials of free radicals of cell suspension extracts. Overall, the outcomes of this study can be utilized for the large scale production of pharmaceutically important secondary metabolites from S. kakudensis through cell suspension cultures.

  16. Effects of enhanced UV-B radiation on secondary metabolites in forage plants and potential consequences for multiple trophic responses involving mammalian herbivores

    Science.gov (United States)

    Thines, Nicole J.; Bassman, John H.; Shipley, Lisa A.; Slusser, James R.

    2004-10-01

    Herbivores represent the interface between primary production and higher trophic levels. The effects of enhanced UV-B radiation on microbes, invertebrate herbivores, and detritivores has received limited study in both terrestrial and aquatic ecosystems. However, although direct effects (e.g. melanoma, cataracts) on mammals have been documented, indirect effects (e.g., resulting from changes in plant chemistry) of enhanced UV-B on mammalian herbivores have not been evaluated. Although the diet of mammalian herbivores has little effect on nutritional quality for their associated predators, to the extent changes in plant chemistry affect aspects of population dynamics (e.g., growth, fecundity, densities), higher trophic levels can be affected. In this study, different forage species of varying inherent levels of key secondary metabolites are being grown in the field under either ambient or ambient plus supplemental UV-B radiation simulating a 15% stratospheric ozone depletion for Pullman, Washington. At various time intervals, foliage is being sampled and analyzed for changes in secondary metabolites and other attributes. Using controlled feeding trials, changes in plant secondary metabolites are being related to preference and digestibility in specialist and generalist mammalian hindgut herbivores, digestion in ruminants and non-ruminants, and to selected aspects of population dynamics in mammalian herbivores. Results suggest how UV-B-induced changes in plant secondary chemistry affect animal nutrition, and thus animal productivity in a range of mammalian herbivores. Reductions in palatability and digestibility of plant material along with reductions in fecundity and other aspects of population dynamics could have significant economic ramifications for farmers, ranchers and wildlife biologists.

  17. Enhanced production of vanillin flavour metabolites by precursor feeding in cell suspension cultures of Decalepis hamiltonii Wight & Arn., in shake flask culture.

    Science.gov (United States)

    Matam, Pradeep; Parvatam, Giridhar; Shetty, Nandini P

    2017-12-01

    The flavour rich tuberous roots of Decalepis hamiltonii are known for its edible and medicinal use and have become endangered due to commercial over-exploitation. Besides 2-Hydroxy-4-methoxy benzaldehyde (2H4MB), other flavour metabolites in tuberous roots include vanillin, 4-Methoxy Cinnamic acid derivatives, aromatic alcohols etc. So far, there are no reports on the pathway of 2H4MB biosynthesis nor there is an organized work on biotransformation using normal and cell suspension cultures for obtaining these metabolites using precursors. The main aim of the study is to develop a method for enhanced production of flavour attributing metabolites through ferulic acid (FA) feeding to the D. hamiltonii callus culture medium. Biomass of D. hamiltonii cell suspension cultures was maximum (200.38 ± 1.56 g/l) by 4th week. Maximum production of 2H4MB was recorded on 4th week (0.08 ± 0.01 mg/100 g dry weight) as quantified by HPLC. Addition of 0.1-1.5 mM ferulic acid as precursor in the culture medium showed significant ( p  vanillin, 2H4MB, vanillic acid, ferulic acid were of 0.1 ± 0.02 mg/100 g, 0.44 ± 0.01 mg/100 g, 0.52 ± 0.04 mg/100 g, 0.18 ± 0.02 mg/100 g DW respectively in 4 weeks of cultured cells supplemented with 1 mM ferulic acid as a precursor. The results indicate that, substantial increase in the levels of flavour metabolites in D. hamiltonii callus suspension culture was achieved. This would be having implications in biosynthesis of respective vanilla flavour attributing metabolites at very high levels for their large scale production.

  18. An extensive case study of hairy-root cultures for enhanced secondary-metabolite production through metabolic-pathway engineering.

    Science.gov (United States)

    Mehrotra, Shakti; Rahman, Laiq Ur; Kukreja, Arun Kumar

    2010-08-23

    An intrinsic improvement is taking place in the methodologies for the development of culture systems with first-rate production of plant-based molecules. The blending of HR (hairy root) cultures with ME (metabolic engineering) approaches offers new insights into, and possibilities for, improving the system productivity for known and/or novel high-value plant-derived active compounds. The introduction and expression of foreign genes in plants results in improvement of cellular activities by manipulating enzymatic, regulatory and transport function of the cell. The rational amendments in the rate-limiting steps of a biosynthetic pathway as well as inactivating the inefficient pathway(s) for by-product formation can be accomplished either through single-step engineering or through the multi-step engineering. The hierarchical control of any metabolic process can lead the engineer to apply the ME ideas and principles to any of the strata, including transcriptional, moving on to translational and enzymatic activity. The HR culture systems offer a remarkable potential for commercial production of a number of low-volume, but high-value, secondary metabolites. Taking HR as a model system, in the present review, we discuss engineering principles and perceptions to exploit secondary-metabolite pathways for the production of important bioactive compounds. We also talk about requisites and possible challenges that occur during ME, with emphasis on examples of various HR systems. Furthermore, it also highlights the utilization of global information obtained from '-omic' platforms in order to explore pathway architecture, structural and functional aspects of important enzymes and genes that can support the design of sets of engineering, resulting in the generation of wide-ranging views of DNA sequence-to-metabolite passageway networking and their control to obtain desired results.

  19. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1.

    Science.gov (United States)

    Kim, Minji; Furuzono, Tomoya; Yamakuni, Kanae; Li, Yongjia; Kim, Young-Il; Takahashi, Haruya; Ohue-Kitano, Ryuji; Jheng, Huei-Fen; Takahashi, Nobuyuki; Kano, Yuriko; Yu, Rina; Kishino, Shigenobu; Ogawa, Jun; Uchida, Kunitoshi; Yamazaki, Jun; Tominaga, Makoto; Kawada, Teruo; Goto, Tsuyoshi

    2017-11-01

    Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota-derived compounds remain to be understood. Therefore, in this study, we investigated the effects of KetoA [10-oxo-12( Z )-octadecenoic acid]-a linoleic acid metabolite produced by gut lactic acid bacteria-on whole-body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet-induced obesity. By using Ca 2+ imaging and whole-cell patch-clamp methods, KetoA was noted to potently activate transient receptor potential vanilloid 1 (TRPV1) and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up-regulated genes that are related to brown adipocyte functions, including uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later diminished in the presence of a β-adrenoreceptor blocker. By using obese and diabetic model KK-Ay mice, we further show that KetoA intake ameliorated obesity-associated metabolic disorders. In the absence of any observed KetoA-induced antiobesity effect or UCP1 up-regulation in TRPV1-deficient mice, we prove that the antiobesity effect of KetoA was caused by TRPV1 activation-mediated browning in WAT. KetoA produced in the gut could therefore be involved in the regulation of host energy metabolism.-Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.-I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. 10-oxo-12( Z )-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1. © FASEB.

  20. The Fungus Aspergillus aculeatus Enhances Salt-Stress Tolerance, Metabolite Accumulation, and Improves Forage Quality in Perennial Ryegrass

    Directory of Open Access Journals (Sweden)

    Xiaoning Li

    2017-09-01

    Full Text Available Perennial ryegrass (Lolium perenne is an important forage grass with high yield and superior quality in temperate regions which is widely used in parks, sport field, and other places. However, perennial ryegrass is moderately tolerant to salinity stress compared to other commercial cultivars and salt stress reduces their growth and productivity. Aspergillus aculeatus has been documented to participate in alleviating damage induced by salinity. Therefore, the objective of this study was to investigate the mechanisms underlying A. aculeatus-mediated salt tolerance, and forage quality of perennial ryegrass exposed to 0, 200, and 400 mM NaCl concentrations. Physiological markers and forage quality of perennial ryegrass to salt stress were evaluated based on the growth rate, photosynthesis, antioxidant enzymes activity, lipid peroxidation, ionic homeostasis, the nutritional value of forage, and metabolites. Plants inoculated with A. aculeatus exhibited higher relative growth rate (RGR, turf and forage quality under salt stress than un-inoculated plants. Moreover, in inoculated plants, the fungus remarkably improved plant photosynthetic efficiency, reduced the antioxidant enzymes activity (POD and CAT, and attenuated lipid peroxidation (decreased H2O2 and MDA accumulation induced by salinity, compared to un-inoculated plants. Furthermore, the fungus also acts as an important role in maintaining the lower Na/K ratio and metabolites and lower the amino acids (Alanine, Proline, GABA, and Asparagine, and soluble sugars (Glucose and Fructose for inoculated plants than un-inoculated ones. Our results suggest that A. aculeatus may be involved in modulating perennial ryegrass tolerance to salinity in various ways.

  1. Pectin Enhances Bio-Control Efficacy by Inducing Colonization and Secretion of Secondary Metabolites by Bacillus amyloliquefaciens SQY 162 in the Rhizosphere of Tobacco.

    Directory of Open Access Journals (Sweden)

    Kai Wu

    Full Text Available Bacillus amyloliquefaciens is a plant-beneficial Gram-positive bacterium involved in suppressing soil-borne pathogens through the secretion of secondary metabolites and high rhizosphere competence. Biofilm formation is regarded as a prerequisite for high rhizosphere competence. In this work, we show that plant extracts affect the chemotaxis and biofilm formation of B. amyloliquefaciens SQY 162 (SQY 162. All carbohydrates tested induced the chemotaxis and biofilm formation of the SQY 162 strain; however, the bacterial growth rate was not influenced by the addition of carbohydrates. A strong chemotactic response and biofilm formation of SQY 162 were both induced by pectin through stimulation of surfactin synthesis and transcriptional expression of biofilm formation related matrix genes. These results suggested that pectin might serve as an environmental factor in the stimulation of the biofilm formation of SQY 162. Furthermore, in pot experiments the surfactin production and the population of SQY 162 in the rhizosphere significantly increased with the addition of sucrose or pectin, whereas the abundance of the bacterial pathogen Ralstonia decreased. With increased production of secondary metabolites in the rhizosphere of tobacco by SQY 162 and improved colonization density of SQY 162 in the pectin treatment, the disease incidences of bacterial wilt were efficiently suppressed. The present study revealed that certain plant extracts might serve as energy sources or environmental cues for SQY 162 to enhance the population density on tobacco root and bio-control efficacy of tobacco bacterial wilt.

  2. Enhanced extraction yields and mobile phase separations by solvent mixtures for the analysis of metabolites in Annona muricata L. leaves.

    Science.gov (United States)

    Ribeiro de Souza, Eloana Benassi; da Silva, Renata Reis; Afonso, Sabrina; Scarminio, Ieda Spacino

    2009-12-01

    The effects of five extraction solvents and their mixtures on the yield of metabolites in crude and fractionated extracts of Annona muricata L. leaves were investigated by direct comparison. Extraction media were prepared using simplex centroid mixtures of ethanol, ethyl acetate, dichloromethane, acetone, and chloroform. The effects of the mobile phase solvent strength and the analysis wavelength on the chromatographic separation were also investigated. Solvent mixtures rather than pure solvents were found to be the most efficient extractors for the different fractions. The results indicated that the mobile phase composed of methanol/acetonitrile/water (26:27:47 v/v/v) was most suitable for the basic fraction analysis at 254 nm, whereas the mobile phase composed of methanol/acetonitrile/water (35:35:30 v/v/v) was the most adequate for the organic fraction analysis at 254 nm. The results indicated that the chromatographic profiles and number of peaks were affected by the mobile phase strength and analysis wavelength.

  3. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...

  4. Detection of bacterial metabolites through dynamic acquisition from surface enhanced raman spectroscopy substrates integtrated in a centrifugal microfluidic platform

    DEFF Research Database (Denmark)

    Durucan, Onur; Morelli, Lidia; Schmidt, Michael Stenbæk

    2015-01-01

    In this work we present a novel technology that combines the advantages of centrifugal microfluidics with dynamic in-situ Surface Enhanced Raman Spectroscopy (SERS) sensing. Our technology is based on an automated readout system that allows on-line SERS acquisition on a rotating centrifugal...

  5. Calcium and potassium supplementation enhanced growth, osmolytes, secondary metabolite production, and enzymatic antioxidant machinery in cadmium-exposed chickpea (Cicer arietinum L.

    Directory of Open Access Journals (Sweden)

    Parvaiz eAhmad

    2016-04-01

    Full Text Available The present work was conducted to examine the role of exogenously applied calcium (Ca; 50 mM and potassium (K; 10 mM (alone and in combination in alleviating the negative effects of cadmium (Cd; 200 μM on growth, biochemical attributes, secondary metabolites and yield of chickpea (Cicer arietinum L.. Cd stress significantly decreased length and fresh and dry weight of shoot and root, and number of pods and seed yield (vs. control. Exhibition of decreases in chlorophyll (Chl a, Chl b, and total Chl was also observed with Cd-exposure when compared to control. However, Cd-exposure led to an increase in the content of carotenoid. In contrast, the exogenous application of Ca and K individually as well as in combination minimized the extent of Cd-impact on previous traits. C. arietinum seedlings subjected to Cd treatment exhibited increased contents of organic solute (proline, Pro and total protein; whereas, Ca and K-supplementation further enhanced the Pro and total protein content. Additionally, compared to control, Cd-exposure also caused elevation in the contents of oxidative stress markers (hydrogen peroxidase, H2O2; malondialdehyde, MDA and in the activity of antioxidant defense enzymes (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; glutathione reductase, GR. Ca, K and Ca + K supplementation caused further enhancements in the activity of these enzymes but significantly decreased contents of H2O2 and MDA, also that of Cd in shoot and root. The contents of total phenol, flavonoid and mineral elements (S, Mn, Mg, Ca and K that were also suppressed in Cd stressed plants in both shoot and root were restored to appreciable levels with Ca- and K-supplementation. However, the combination of Ca + K supplementation was more effective in bringing the positive response as compared to individual effect of Ca and K on Cd-exposed C. arietinum. Overall, this investigation suggests that application of Ca and/or K can efficiently minimize

  6. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Directory of Open Access Journals (Sweden)

    Yun Sun Lee

    Full Text Available Aloe vera (Asphodeloideae is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  7. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Science.gov (United States)

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  8. Detection of bacterial metabolites through dynamic acquisition from surface enhanced raman spectroscopy substrates integtrated in a centrifugal microfluidic platform

    DEFF Research Database (Denmark)

    Durucan, Onur; Morelli, Lidia; Schmidt, Michael Stenbæk

    2015-01-01

    In this work we present a novel technology that combines the advantages of centrifugal microfluidics with dynamic in-situ Surface Enhanced Raman Spectroscopy (SERS) sensing. Our technology is based on an automated readout system that allows on-line SERS acquisition on a rotating centrifugal...... microfluidic platform with embedded gold nanopillar substrates. While spinning, the disc platform enables dynamic SERS acquisition of multiple chips, significantly reducing time-to-result and improving the reproducibility of the acquired spectra, reducing the fluctuation by a factor of 2....

  9. Over-expression of DXS gene enhances terpenoidal secondary metabolite accumulation in rose-scented geranium and Withania somnifera: active involvement of plastid isoprenogenic pathway in their biosynthesis.

    Science.gov (United States)

    Jadaun, Jyoti Singh; Sangwan, Neelam S; Narnoliya, Lokesh K; Singh, Neha; Bansal, Shilpi; Mishra, Bhawana; Sangwan, Rajender Singh

    2017-04-01

    Rose-scented geranium (Pelargonium spp.) is one of the most important aromatic plants and is well known for its diverse perfumery uses. Its economic importance is due to presence of fragrance rich essential oil in its foliage. The essential oil is a mixture of various volatile phytochemicals which are mainly terpenes (isoprenoids) in nature. In this study, on the geranium foliage genes related to isoprenoid biosynthesis (DXS, DXR and HMGR) were isolated, cloned and confirmed by sequencing. Further, the first gene of 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, 1-deoxy-d-xylulose-5-phosphate synthase (GrDXS), was made full length by using rapid amplification of cDNA ends strategy. GrDXS contained a 2157 bp open reading frame that encoded a polypeptide of 792 amino acids having calculated molecular weight 77.5 kDa. This study is first report on heterologous expression and kinetic characterization of any gene from this economically important plant. Expression analysis of these genes was performed in different tissues as well as at different developmental stages of leaves. In response to external elicitors, such as methyl jasmonate, salicylic acid, light and wounding, all the three genes showed differential expression profiles. Further GrDXS was over expressed in the homologous (rose-scented geranium) as well as in heterologous (Withania somnifera) plant systems through genetic transformation approach. The over-expression of GrDXS led to enhanced secondary metabolites production (i.e. essential oil in rose-scented geranium and withanolides in W. somnifera). To the best of our knowledge, this is the first report showing the expression profile of the three genes related to isoprenoid biosynthesis pathways operated in rose-scented geranium as well as functional characterization study of any gene from rose-scented geranium through a genetic transformation system. © 2016 Scandinavian Plant Physiology Society.

  10. The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway.

    Science.gov (United States)

    Nishizaki, Tomoyuki; Matsumura, Takuro

    2002-01-31

    The present study was conducted to assess the effect of aniracetam and its metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3), and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2-Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300 microM, with a maximal effect at 100 microM. The potentiation was long-lasting, reaching approximately 180% of basal levels 60 min after 5-min treatment with 2-pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3 channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2 currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents, but to a lesser extent, each about 130 and 103% of basal levels 60 min after treatment at 100 microM. In contrast, anisamide butyrate had no potentiating effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with 2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective inhibitor of cAMP-dependent protein kinase. The results of the present study suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.

  11. Microbial production of primary metabolites

    Science.gov (United States)

    Demain, Arnold L.

    1980-12-01

    Microbial production of primary metabolites contributes significantly to the quality of life. Through fermentation, microorganisms growing on inexpensive carbon sources can produce valuable products such as amino acids, nucleotides, organic acids, and vitamins which can be added to food to enhance its flavor or increase its nutritive value. The contribution of microorganisms will go well beyond the food industry with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum-derived products as well as the ethanol necessary for liquid fuel. The role of primary metabolites and the microbes which produce them will certainly increase in importance.

  12. Design of a fused phantom for quantitative evaluation of brain metabolites and enhanced quality assurance testing for magnetic resonance imaging and spectroscopy.

    Science.gov (United States)

    Song, Kyu-Ho; Kim, Sang-Young; Lee, Do-Wan; Jung, Jin-Young; Lee, Jung-Hoon; Baek, Hyeon-Man; Choe, Bo-Young

    2015-11-30

    Magnetic resonance imaging and spectroscopy (MRI-MRS) is a useful tool for the identification and evaluation of chemical changes in anatomical regions. Quality assurance (QA) is performed in either images or spectra using QA phantom. Therefore, consistent and uniform technical MRI-MRS QA is crucial. Here we developed an MRI-MRS fused phantom along with the inserts for metabolite quantification to simultaneously optimize QA parameters for both MRI and MRS. T1- and T2-weighted images were obtained and MRS was performed with point-resolved spectroscopy. Using the fused phantom, the results of measuring MRI factors were: geometric distortion, phantoms could not obtain information from both images and spectra in the MR scanner simultaneously. Here we designed and developed a phantom for accurate and consistent QA within the acceptance range. It is important to take into account variations in the QA value using the MRI-MRS phantom, when comparing to other clinical or research MR scanners. The MRI-MRS QA factors obtained simultaneously using the phantom can facilitate evaluation of both images and spectra, and provide guidelines for obtaining MRI and MRS QA factors simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Surfactant Supplementation to Enhance the Production of Vitamin K2 Metabolites in Shake Flask Cultures Using Escherichia sp. Mutant FM3-1709

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2014-01-01

    Full Text Available The effects of the addition of various surfactants on the cell growth and production of vitamin K2 metabolites, such as intracellular menaquinone-4 (MK-4, extracellular MK-4, intracellular MK-6 and extracellular MK-6, were studied in the submerged culture of Escherichia sp. All of the added surfactants caused the extension of the exponential phase. Betaine, polyoxyethylene oleyl ether and Tween-80 were favourable to the cell growth of Escherichia sp. mutant strain FM3-1709. The highest cell growth (Xmax, biomass production rate (Qx and biomass yield (Yx/s were (12.6±0.2 g/L, (0.21±0.01 g/(L·h and (2.42± 0.02 g/g, respectively. The results show that the addition of all surfactants led to a lower production of intracellular MK-4, whereas the production of extracellular MK-4 increased remarkably. Among the five investigated surfactants, the addition of the nonionic surfactant polyoxyethylene oleyl ether (1.0 g/L led to the highest production of extracellular MK-4 ((33.6±0.4 mg/L, MK-6 ((2.56±0.07 mg/L and the highest yield of total MK-4 ((47.6±0.4 mg/L and MK-6 ((6.0±0.1 mg/L. The addition of polyoxyethylene oleyl ether proved to be more beneficial for the secretion of MK-4 than MK-6.

  14. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  16. Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase η.

    Science.gov (United States)

    Patra, Amritraj; Politica, Dustin A; Chatterjee, Arindom; Tokarsky, E John; Suo, Zucai; Basu, Ashis K; Stone, Michael P; Egli, Martin

    2016-11-03

    The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  18. Mutagenic azide metabolite is azidoalanine

    International Nuclear Information System (INIS)

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  19. [Antiviral properties of basidiomycetes metabolites].

    Science.gov (United States)

    Avtonomova, A V; Krasnopolskaya, L M

    2014-01-01

    The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity.

  20. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  1. Secondary metabolites from bromeliaceae family

    OpenAIRE

    Manetti, Liliana Maria; Delaporte, Rosemeres Horwat; Laverde Jr., Antonio

    2009-01-01

    This review describes aspects of the Bromeliaceae family dealing the traditional applications, biological activities and distribution of secondary metabolites in distinct subfamilies. Some species are used with medicinal purposed in the treatment of respiratory, diabetes or inflammation diseases, and gastrointestinal disorders. Special emphasis on cycloartane triterpenoids and flavonoids, typical metabolites of this family, are presented. Bromeliaceae is unique amongst the monocotyledons in t...

  2. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  3. Bignoniaceae Metabolites as Semiochemicals

    Directory of Open Access Journals (Sweden)

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  4. Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness

    NARCIS (Netherlands)

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.M.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2015-01-01

    Whilst development of medium and feeds has provided major advances in recombinant protein production in CHO cells, the fundamental understanding is limited. We have applied metabolite profiling with established robust (GC-MS) analytics to define the molecular loci by which two yield-enhancing feeds

  5. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  6. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  7. Primary expectations of secondary metabolites

    Science.gov (United States)

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  8. Metabolite profiles of common Stemphylium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    Thirty-three isolates of Stemphylium spp. have been analysed for their metabolite profiles. Five metabolites, stemphylin, stemphyloxin II, stemphyperylenol, stemphol and a stemphol related compound, have been detected by high-performance liquid chromatography and thin-layer chromatography...

  9. Detection of 191 Taxifolin Metabolites and Their Distribution in Rats Using HPLC-ESI-IT-TOF-MSn

    Directory of Open Access Journals (Sweden)

    Ping Yang

    2016-09-01

    Full Text Available Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSn method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives.

  10. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Science.gov (United States)

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  11. Abnormal Metabolite in Alcoholic Subjects,

    Science.gov (United States)

    1982-01-01

    0.01 0.12 81 A.A. 51 M 0 ɘ.01 0.09 Schizophrenia 85a W.G. 67 M 0 ɘ.01 0.21 Proteins & Ketones in Urine b 0 ɘ.01 0.11 86a W.H. 67 M 0 ɘ.01 0.15 b 0...AD-AS 90 TOTTS GAP MEDICAL RESEARCH LABS INC BANGOR PA F/G 6/5 ABNORMAL METABOLITE IN ALCOHOLIC SUBJECTS, U) 1982 R L BEECH, M E FELVER, M R...LAKSCHMANAN NOOBIN 70 C 0233 UNJCLASSIFIED NL I ,I/ ABNORMAL METABOLITE IN ALCOHOLIC SUBJECTS Richard L . Veech, Michael E. Felver, M.R. Lakschmanan, Stewart

  12. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Chromatographic analysis of tryptophan metabolites.

    Science.gov (United States)

    Sadok, Ilona; Gamian, Andrzej; Staniszewska, Magdalena Maria

    2017-08-01

    The kynurenine pathway generates multiple tryptophan metabolites called collectively kynurenines and leads to formation of the enzyme cofactor nicotinamide adenine dinucleotide. The first step in this pathway is tryptophan degradation, initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase, or tryptophan 2,3-dioxygenase, depending on the tissue. The balanced kynurenine metabolism, which has been a subject of multiple studies in last decades, plays an important role in several physiological and pathological conditions such as infections, autoimmunity, neurological disorders, cancer, cataracts, as well as pregnancy. Understanding the regulation of tryptophan depletion provide novel diagnostic and treatment opportunities, however it requires reliable methods for quantification of kynurenines in biological samples with complex composition (body fluids, tissues, or cells). Trace concentrations, interference of sample components, and instability of some tryptophan metabolites need to be addressed using analytical methods. The novel separation approaches and optimized extraction protocols help to overcome difficulties in analyzing kynurenines within the complex tissue material. Recent developments in chromatography coupled with mass spectrometry provide new opportunity for quantification of tryptophan and its degradation products in various biological samples. In this review, we present current accomplishments in the chromatographic methodologies proposed for detection of tryptophan metabolites and provide a guide for choosing the optimal approach. © 2017 The Authors. Journal of Separation Science published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Patulin and secondary metabolite production by marine-derived Penicillium strains

    DEFF Research Database (Denmark)

    Vansteelandt, Marieke; Kerzaon, Isabelle; Blanchet, Elodie

    2012-01-01

    )–mass spectrometry (MS)/MS. Each strain was grown on six different culture media to enhance the number of observable metabolites.Thirty-two secondary metabolites were detected in crude extracts with twenty first observations for studied species. Patulin, a major mycotoxin, was classically detected in extracts...... of these fungi in shellfish farming areas.Patulin induced acute neurotoxicity on Diptera larvae, indicating the interest of this bioassay as an additional tool for detection of this major mycotoxin in crude extracts....

  15. Metabolite

    Science.gov (United States)

    Kumar V, Abbas AK, Aster JC. Cellular responses to stress and toxic insults: adaptation, injury, and death. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease . 9th ed. Philadelphia, PA: ...

  16. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Science.gov (United States)

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Epigenome targeting by probiotic metabolites

    Directory of Open Access Journals (Sweden)

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  18. Purine metabolites in fibromyalgia syndrome.

    Science.gov (United States)

    Fais, A; Cacace, E; Corda, M; Era, B; Peri, M; Utzeri, S; Ruggiero, V

    2013-01-01

    To evaluate serum purine metabolite concentrations in patients affected by fibromyalgia syndrome (FMS) and the relationships between their levels and FM clinical parameters. Serum purine levels were quantified using LC/UV-vis in 22 fibromyalgic females (according to the American College of Rheumatology classification criteria) and 22 healthy females. Significantly higher serum inosine, hypoxanthine and xanthine levels (pFibromyalgia Impact Questionnaire (FIQ). Study results suggest that purines, in particular adenosine and inosine, may be involved in pain transmission in fibromyalgia. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http......://www.secondarymetabolites.org) is introduced to provide a one-stop catalog and links to these bioinformatics resources. In addition, an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field....

  20. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  1. of Several Organophosphorus Insecticide Metabolites

    Directory of Open Access Journals (Sweden)

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  2. Metabolites from Alternaria Fungi and Their Bioactivities

    Directory of Open Access Journals (Sweden)

    Ligang Zhou

    2013-05-01

    Full Text Available Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed.

  3. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  4. Antimycobacterial Metabolites from Marine Invertebrates.

    Science.gov (United States)

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Selected Secondary Plant Metabolites for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2015-01-01

    Full Text Available Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.

  6. Microsomal metabolism of trenbolone acetate metabolites ...

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  7. Biochemical and secondary metabolites changes under moisture ...

    African Journals Online (AJOL)

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  8. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut...... microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... in adipose tissue, the liver, and the endocrine pancreas. Importantly, distinct metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance...

  9. Spectroscopic methods to analyze drug metabolites.

    Science.gov (United States)

    Yi, Jong-Jae; Park, Kyeongsoon; Kim, Won-Je; Rhee, Jin-Kyu; Son, Woo Sung

    2018-03-09

    Drug metabolites have been monitored with various types of newly developed techniques and/or combination of common analytical methods, which could provide a great deal of information on metabolite profiling. Because it is not easy to analyze whole drug metabolites qualitatively and quantitatively, a single solution of analytical techniques is combined in a multilateral manner to cover the widest range of drug metabolites. Mass-based spectroscopic analysis of drug metabolites has been expanded with the help of other parameter-based methods. The current development of metabolism studies through contemporary pharmaceutical research are reviewed with an overview on conventionally used spectroscopic methods. Several technical approaches for conducting drug metabolic profiling through spectroscopic methods are discussed in depth.

  10. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  11. Complicating factors in safety testing of drug metabolites: kinetic differences between generated and preformed metabolites.

    Science.gov (United States)

    Prueksaritanont, Thomayant; Lin, Jiunn H; Baillie, Thomas A

    2006-12-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

  12. Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

    Science.gov (United States)

    Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

    2011-02-28

    3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Analytical methodologies for broad metabolite coverage of exhaled breath condensate.

    Science.gov (United States)

    Aksenov, Alexander A; Zamuruyev, Konstantin O; Pasamontes, Alberto; Brown, Joshua F; Schivo, Michael; Foutouhi, Soraya; Weimer, Bart C; Kenyon, Nicholas J; Davis, Cristina E

    2017-09-01

    Breath analysis has been gaining popularity as a non-invasive technique that is amenable to a broad range of medical uses. One of the persistent problems hampering the wide application of the breath analysis method is measurement variability of metabolite abundances stemming from differences in both sampling and analysis methodologies used in various studies. Mass spectrometry has been a method of choice for comprehensive metabolomic analysis. For the first time in the present study, we juxtapose the most commonly employed mass spectrometry-based analysis methodologies and directly compare the resultant coverages of detected compounds in exhaled breath condensate in order to guide methodology choices for exhaled breath condensate analysis studies. Four methods were explored to broaden the range of measured compounds across both the volatile and non-volatile domain. Liquid phase sampling with polyacrylate Solid-Phase MicroExtraction fiber, liquid phase extraction with a polydimethylsiloxane patch, and headspace sampling using Carboxen/Polydimethylsiloxane Solid-Phase MicroExtraction (SPME) followed by gas chromatography mass spectrometry were tested for the analysis of volatile fraction. Hydrophilic interaction liquid chromatography and reversed-phase chromatography high performance liquid chromatography mass spectrometry were used for analysis of non-volatile fraction. We found that liquid phase breath condensate extraction was notably superior compared to headspace extraction and differences in employed sorbents manifested altered metabolite coverages. The most pronounced effect was substantially enhanced metabolite capture for larger, higher-boiling compounds using polyacrylate SPME liquid phase sampling. The analysis of the non-volatile fraction of breath condensate by hydrophilic and reverse phase high performance liquid chromatography mass spectrometry indicated orthogonal metabolite coverage by these chromatography modes. We found that the metabolite coverage

  14. Biosynthesis of human diazepam and clonazepam metabolites.

    Science.gov (United States)

    de Paula, Núbia C; Araujo Cordeiro, Kelly C F; de Melo Souza, Paula L; Nogueira, Diogo F; da Silva e Sousa, Diego B; Costa, Maísa B; Noël, François; de Oliveira, Valéria

    2015-03-01

    A screening of fungal and microbial strains allowed to select the best microorganisms to produce in high yields some of the human metabolites of two benzodiazepine drugs, diazepam and clonazepam, in order to study new pharmacological activities and for chemical standard proposes. Among the microorganisms tested, Cunninghamella echinulata ATCC 9244 and Rhizopus arrhizus ATCC 11145 strains, were the most active producers of the mains metabolites of diazepam which included demethylated, hydroxylated derivatives. Beauveria bassiana ATCC 7159 and Chaetomium indicum LCP 984200 produced the 7 amino-clonazepam metabolite and a product of acid hydrolysis of this benzodiazepine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Coping with shrub secondary metabolites by ruminants

    Science.gov (United States)

    Rangelands throughout the world contain varying but often substantial proportions of shrubs. Shrubs are generally heavily chemically defended, and herbivores must either contend with their plant secondary metabolites (PSM) or avoid a significant component of the available forage. Browsing ruminants ...

  16. The Membrane Gradostat Reactor: Secondary metabolite production ...

    African Journals Online (AJOL)

    SERVER

    2007-05-16

    May 16, 2007 ... immobilise microbial cells or enzymes, depending on the bioreactor's application. Operational ... perspective. Key words: Membrane bioreactor, gradostat reactor, secondary metabolite production, biofilm, wastewater treatment. INTRODUCTION ... suitable to immobilize P. chrysosporium biofilms in MGR.

  17. Metabolite production by species of Stemphylium.

    Science.gov (United States)

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    Morphology and phylogeny have been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species of fungi is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while also exploring the potential of chemotaxonomy as a robust identification method for Stemphylium. Several species were found to have species-specific metabolites, while other species were distinguishable by a broader metabolic profile rather than specific metabolites. Many previously described metabolites were found to be important for distinguishing species, while some unknown metabolites were also determined to have important roles in distinguishing species of Stemphylium. This study is the first of its kind to investigate the chemical potential of Stemphylium across the whole genus. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  18. Biologically Active Secondary Metabolites from the Fungi.

    Science.gov (United States)

    Bills, Gerald F; Gloer, James B

    2016-11-01

    Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly limitless potential for metabolic variation and an untapped resource for drug discovery and synthetic biology. Much of the ecological success of the filamentous fungi in colonizing the planet is owed to their ability to deploy their secondary metabolites in concert with their penetrative and absorptive mode of life. Fungal secondary metabolites exhibit biological activities that have been developed into life-saving medicines and agrochemicals. Toxic metabolites, known as mycotoxins, contaminate human and livestock food and indoor environments. Secondary metabolites are determinants of fungal diseases of humans, animals, and plants. Secondary metabolites exhibit a staggering variation in chemical structures and biological activities, yet their biosynthetic pathways share a number of key characteristics. The genes encoding cooperative steps of a biosynthetic pathway tend to be located contiguously on the chromosome in coregulated gene clusters. Advances in genome sequencing, computational tools, and analytical chemistry are enabling the rapid connection of gene clusters with their metabolic products. At least three fungal drug precursors, penicillin K and V, mycophenolic acid, and pleuromutilin, have been produced by synthetic reconstruction and expression of respective gene clusters in heterologous hosts. This review summarizes general aspects of fungal secondary metabolism and recent developments in our understanding of how and why fungi make secondary metabolites, how these molecules are produced, and how their biosynthetic genes are distributed across the Fungi. The breadth of fungal secondary metabolite diversity is highlighted by recent information on the biosynthesis of important fungus-derived metabolites that have contributed to human health and agriculture and that have negatively impacted crops

  19. Functions of secondary metabolites of lichens

    OpenAIRE

    Zvěřinová, Gabriela

    2014-01-01

    This bachelor thesis is a review of available literature about lichen secondary metabolites and their functions. Lichens produce a great variety of these compounds; most of them are unique to the lichen symbiosis and are not found in higher plants. Besides the role of these compounds in chemotaxonomy and systematics, lichen secondary metabolites exhibit various biological functions and can affect biotic and abiotic interactions of lichens with their environment. Well-known and often described...

  20. Hydrophobicity and charge shape cellular metabolite concentrations.

    Directory of Open Access Journals (Sweden)

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  1. Secondary metabolites in bryophytes: an ecological aspect.

    Science.gov (United States)

    Xie, Chun-Feng; Lou, Hong-Xiang

    2009-03-01

    Bryophytes frequently grow in an unfavorable environment as the earliest land plants, and inevitably biosynthesize secondary metabolites against biotic or abiotic stress. They not only defend against the plant competition, microbial attack, and insect or animal predation, but also function in UV protection, drought tolerance, and freezing survival. This review covers the ecological aspect of secondary metabolites in bryophytes and is taxonomically presented according to the ecological significances.

  2. Quantification of a bacterial secondary metabolite by SERS combined with SLM extraction for bioprocess monitoring

    DEFF Research Database (Denmark)

    Morelli, Lidia; Andreasen, Sune Zoëga; Jendresen, Christian Bille

    2017-01-01

    and combined it with surface enhanced Raman scattering (SERS) sensing for the screening of a biological process, namely for the quantification of a bacterial secondary metabolite, p-coumaric acid (pHCA), produced by Escherichia coli. The microfluidic device proved to be robust and reusable, enabling efficient....... The obtained data showed good correlation with HPLC analysis....

  3. Uncovering Potential Applications of Cyanobacteria and Algal Metabolites in Biology, Agriculture and Medicine: Current Status and Future Prospects.

    Science.gov (United States)

    Singh, Rachana; Parihar, Parul; Singh, Madhulika; Bajguz, Andrzej; Kumar, Jitendra; Singh, Samiksha; Singh, Vijay P; Prasad, Sheo M

    2017-01-01

    Cyanobacteria and algae having complex photosynthetic systems can channelize absorbed solar energy into other forms of energy for production of food and metabolites. In addition, they are promising biocatalysts and can be used in the field of "white biotechnology" for enhancing the sustainable production of food, metabolites, and green energy sources such as biodiesel. In this review, an endeavor has been made to uncover the significance of various metabolites like phenolics, phytoene/terpenoids, phytols, sterols, free fatty acids, photoprotective compounds (MAAs, scytonemin, carotenoids, polysaccharides, halogenated compounds, etc.), phytohormones, cyanotoxins, biocides (algaecides, herbicides, and insecticides) etc. Apart from this, the importance of these metabolites as antibiotics, immunosuppressant, anticancer, antiviral, anti-inflammatory agent has also been discussed. Metabolites obtained from cyanobacteria and algae have several biotechnological, industrial, pharmaceutical, and cosmetic uses which have also been discussed in this review along with the emerging technology of their harvesting for enhancing the production of compounds like bioethanol, biofuel etc. at commercial level. In later sections, we have discussed genetically modified organisms and metabolite production from them. We have also briefly discussed the concept of bioprocessing highlighting the functioning of companies engaged in metabolites production as well as their cost effectiveness and challenges that are being addressed by these companies.

  4. Uncovering Potential Applications of Cyanobacteria and Algal Metabolites in Biology, Agriculture and Medicine: Current Status and Future Prospects

    Directory of Open Access Journals (Sweden)

    Vijay P. Singh

    2017-04-01

    Full Text Available Cyanobacteria and algae having complex photosynthetic systems can channelize absorbed solar energy into other forms of energy for production of food and metabolites. In addition, they are promising biocatalysts and can be used in the field of “white biotechnology” for enhancing the sustainable production of food, metabolites, and green energy sources such as biodiesel. In this review, an endeavor has been made to uncover the significance of various metabolites like phenolics, phytoene/terpenoids, phytols, sterols, free fatty acids, photoprotective compounds (MAAs, scytonemin, carotenoids, polysaccharides, halogenated compounds, etc., phytohormones, cyanotoxins, biocides (algaecides, herbicides, and insecticides etc. Apart from this, the importance of these metabolites as antibiotics, immunosuppressant, anticancer, antiviral, anti-inflammatory agent has also been discussed. Metabolites obtained from cyanobacteria and algae have several biotechnological, industrial, pharmaceutical, and cosmetic uses which have also been discussed in this review along with the emerging technology of their harvesting for enhancing the production of compounds like bioethanol, biofuel etc. at commercial level. In later sections, we have discussed genetically modified organisms and metabolite production from them. We have also briefly discussed the concept of bioprocessing highlighting the functioning of companies engaged in metabolites production as well as their cost effectiveness and challenges that are being addressed by these companies.

  5. Uncovering Potential Applications of Cyanobacteria and Algal Metabolites in Biology, Agriculture and Medicine: Current Status and Future Prospects

    Science.gov (United States)

    Singh, Rachana; Parihar, Parul; Singh, Madhulika; Bajguz, Andrzej; Kumar, Jitendra; Singh, Samiksha; Singh, Vijay P.; Prasad, Sheo M.

    2017-01-01

    Cyanobacteria and algae having complex photosynthetic systems can channelize absorbed solar energy into other forms of energy for production of food and metabolites. In addition, they are promising biocatalysts and can be used in the field of “white biotechnology” for enhancing the sustainable production of food, metabolites, and green energy sources such as biodiesel. In this review, an endeavor has been made to uncover the significance of various metabolites like phenolics, phytoene/terpenoids, phytols, sterols, free fatty acids, photoprotective compounds (MAAs, scytonemin, carotenoids, polysaccharides, halogenated compounds, etc.), phytohormones, cyanotoxins, biocides (algaecides, herbicides, and insecticides) etc. Apart from this, the importance of these metabolites as antibiotics, immunosuppressant, anticancer, antiviral, anti-inflammatory agent has also been discussed. Metabolites obtained from cyanobacteria and algae have several biotechnological, industrial, pharmaceutical, and cosmetic uses which have also been discussed in this review along with the emerging technology of their harvesting for enhancing the production of compounds like bioethanol, biofuel etc. at commercial level. In later sections, we have discussed genetically modified organisms and metabolite production from them. We have also briefly discussed the concept of bioprocessing highlighting the functioning of companies engaged in metabolites production as well as their cost effectiveness and challenges that are being addressed by these companies. PMID:28487674

  6. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

    Science.gov (United States)

    Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

    2018-02-05

    Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Metabolites of cannabidiol identified in human urine.

    Science.gov (United States)

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  8. 40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Metabolites, degradates, contaminants.../Benefit Information § 159.179 Metabolites, degradates, contaminants, and impurities. (a) Metabolites and degradates. Information which shows the existence of any metabolite or degradate of a pesticide product must...

  9. Plant metabolites and nutritional quality of vegetables.

    Science.gov (United States)

    Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

    2008-05-01

    Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

  10. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  11. Secondary metabolites in fungus-plant interactions

    Science.gov (United States)

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

  12. Differential metabolite profiles during fruit development in high-yielding oil palm mesocarp.

    Directory of Open Access Journals (Sweden)

    Huey Fang Teh

    Full Text Available To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes.

  13. Nontargeted metabolite profiles and sensory properties of strawberry cultivars grown both organically and conventionally.

    Science.gov (United States)

    Kårlund, Anna; Hanhineva, Kati; Lehtonen, Marko; Karjalainen, Reijo O; Sandell, Mari

    2015-01-28

    Strawberry (Fragaria × ananassa Duch.) contains many secondary metabolites potentially beneficial for human health, and several of these compounds contribute to strawberry sensory properties, as well. In this study, three strawberry cultivars grown both conventionally and organically were subjected to nontargeted metabolite profiling analysis with LC-qTOF-ESI-MS and to descriptive sensory evaluation by a trained panel. Combined metabolome and sensory data (PLS model) revealed that 79% variation in the metabolome explained 88% variation in the sensory profiles. Flavonoids and condensed and hydrolyzable tannins determined the orosensory properties, and fatty acids contributed to the odor attributes of strawberry. Overall, the results indicated that the chemical composition and sensory quality of strawberries grown in different cultivation systems vary mostly according to cultivar. Organic farming practices may enhance the accumulation of some plant metabolites in specific strawberry genotypes. Careful cultivar selection is a key factor for the improvement of nutritional quality and marketing value of organic strawberries.

  14. Towards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolites.

    Science.gov (United States)

    Mouden, Sanae; Klinkhamer, Peter G L; Choi, Young Hae; Leiss, Kirsten A

    2017-01-01

    With mounting concerns over health and environmental effects of pesticides, the search for environmentally acceptable substitutes has amplified. Plant secondary metabolites appear in the horizon as an attractive solution for green crop protection. This paper reviews the need for changes in the techniques and compounds that, until recently, have been the mainstay for dealing with pest insects. Here we describe and discuss main strategies for selecting plant-derived metabolites as candidates for sustainable agriculture. The second part surveys ten important insecticidal compounds, with special emphasis on those involved in human health. Many of these insecticidal metabolites, however, are crystalline solids with limited solubility which might potentially hamper commercial formulation. As such, we introduce the concept of natural deep eutectic solvents for enhancing solubility and stability of such compounds. The concept, principles and examples of green pest control discussed here offer a new suite of environmental-friendly tools designed to promote and adopt sustainable agriculture.

  15. Pharmacokinetics of aniracetam and its metabolites in rats.

    Science.gov (United States)

    Ogiso, T; Iwaki, M; Tanino, T; Ikeda, K; Paku, T; Horibe, Y; Suzuki, H

    1998-05-01

    The pharmacokinetics of aniracetam (AP), a new cognitive performance enhancer, and its main metabolites was investigated after intravenous (iv) and oral administrations to rat. The plasma levels of AP, 4-p-anisamidobutyric acid (ABA), and p-anisic acid (AA) were determined simultaneously by the HPLC method. The plasma concentrations of the parent drug and ABA quickly declined in a biexponential manner, with rapid terminal decay and a small mean residence time. However, AA yielded nonlinearly high levels at the initial times and the plasma concentrations of 2-pyrrolidinone (PD) were sustained over a relatively long time. When AA was administered intravenously, nonlinearity of the plasma concentrations was also found at higher doses. To describe the time course of the plasma levels of AP and its metabolites after iv administration, a pharmacokinetic model with seven compartments was applied, which included 10 first-order rate constants and one Michaelis-Menten constant. An approximate fit was obtained between the observed and calculated curves based on the model, except for the plasma concentrations of ABA. The plasma concentration-time profiles of AP and its metabolites following oral administration of AP (50 and 100 mg/kg) were similar to those after iv dosing, with the exception of PD, which showed much lower plasma levels than those after iv administration. Elimination of AP and ABA was rapid after oral dosing, and the bioavailability of AP was extremely small (11.4 and 8.6%). As a result, AP was largely metabolized to ABA, AA, and PD in rat.

  16. Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling.

    Science.gov (United States)

    Vijayendran, Chandran; Barsch, Aiko; Friehs, Karl; Niehaus, Karsten; Becker, Anke; Flaschel, Erwin

    2008-04-10

    Evolutionary changes that are due to different environmental conditions can be examined based on the various molecular aspects that constitute a cell, namely transcript, protein, or metabolite abundance. We analyzed changes in transcript and metabolite abundance in evolved and ancestor strains in three different evolutionary conditions - excess nutrient adaptation, prolonged stationary phase adaptation, and adaptation because of environmental shift - in two different strains of bacterium Escherichia coli K-12 (MG1655 and DH10B). Metabolite profiling of 84 identified metabolites revealed that most of the metabolites involved in the tricarboxylic acid cycle and nucleotide metabolism were altered in both of the excess nutrient evolved lines. Gene expression profiling using whole genome microarray with 4,288 open reading frames revealed over-representation of the transport functional category in all evolved lines. Excess nutrient adapted lines were found to exhibit greater degrees of positive correlation, indicating parallelism between ancestor and evolved lines, when compared with prolonged stationary phase adapted lines. Gene-metabolite correlation network analysis revealed over-representation of membrane-associated functional categories. Proteome analysis revealed the major role played by outer membrane proteins in adaptive evolution. GltB, LamB and YaeT proteins in excess nutrient lines, and FepA, CirA, OmpC and OmpA in prolonged stationary phase lines were found to be differentially over-expressed. In summary, we report the vital involvement of energy metabolism and membrane-associated functional categories in all of the evolutionary conditions examined in this study within the context of transcript, outer membrane protein, and metabolite levels. These initial data obtained may help to enhance our understanding of the evolutionary process from a systems biology perspective.

  17. Simvastatin (SV) metabolites in mouse tissues

    International Nuclear Information System (INIS)

    Duncan, C.A.; Vickers, S.

    1990-01-01

    SV, a semisynthetic analog of lovastatin, is hydrolyzed in vivo to its hydroxy acid (SVA), a potent inhibitor of HMG CoA reductase (HR). Thus SV lowers plasma cholesterol. SV is a substrate for mixed function oxidases whereas SVA undergoes lactonization and β-oxidation. Male CD-1 mice were dosed orally with a combination of ( 14 C)SV and ( 3 H)SVA at 25 mg/kg of each, bled and killed at 0.5, 2 and 4 hours. Labeled SV, SVA, 6'exomethylene SV (I), 6'CH 2 OH-SV (II), 6'COOH-SV (III) and a β-oxidized metabolite (IV) were assayed in liver, bile, kidneys, testes and plasma by RIDA. Levels of potential and active HR inhibitors in liver were 10 to 40 fold higher than in other tissues. II and III, in which the configuration at 6' is inverted, may be 2 metabolites of I. Metabolites I-III are inhibitors of HR in their hydroxy acid forms. Qualitatively ( 14 C)SV and ( 3 H)SVA were metabolized similarly (consistent with their proposed interconversion). However 3 H-SVA, I-III (including hydroxy acid forms) achieved higher concentrations than corresponding 14 C compounds (except in gall bladder bile). Major radioactive metabolites in liver were II-IV (including hydroxy acid forms). These metabolites have also been reported in rat tissues. In bile a large fraction of either label was unidentified polar metabolites. The presence of IV indicated that mice (like rats) are not good models for SV metabolism in man

  18. Human pharmacokinetics of proguanil and its metabolites

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Ravn, P; Rønn, A

    1987-01-01

    The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds...... of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total...

  19. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  20. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  1. METABOLITE CHARACTERIZATION IN SERUM SAMPLES FROM ...

    African Journals Online (AJOL)

    Preferred Customer

    and 13C chemical shifts is given in Table 1. Table 1. Resonance assignments of most significant metabolites of serum control healthy samples. S. No Metabolite. Group. 1H shift 13C shift Multiplicities. 1 Fatty acids. CH3. 0.90. 19.7 t. 2 Isoleucine. δCH3. 0.94. 13.8 t. 3 Leucine. δCH3. 0.95. 23.5 d. 4 Leucine. δCH3. 0.96. 24.7.

  2. Metabolite production by species of Stemphylium

    DEFF Research Database (Denmark)

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    2018-01-01

    Morphology and phylogeny has been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while...... also exploring the potential of chemotaxonomy as a robust identification method for Stemphylium. Several species were found to have species-specific metabolites, while other species were distinguishable by a broader metabolic profile rather than specific metabolites. Many previously described...

  3. The effects of GA and ABA treatments on metabolite profile of germinating barley.

    Science.gov (United States)

    Huang, Yuqing; Cai, Shengguan; Ye, Lingzhen; Hu, Hongliang; Li, Chengdao; Zhang, Guoping

    2016-02-01

    Sugar degradation during grain germination is important for malt quality. In malting industry, gibberellin (GA) is frequently used for improvement of malting quality. In this study, the changes of metabolite profiles and starch-degrading enzymes during grain germination, and as affected by GA and abscisic acid (ABA) were investigated using two wild barley accessions XZ72 and XZ95. Totally fifty-two metabolites with known structures were detected and the change of metabolite during germination was time- and genotype dependent. Sugars and amino acids were the most dramatically changed compounds. Addition of GA enhanced the activities of starch-degrading enzymes, and increased most metabolites, especially sugars and amino acids, whereas ABA had the opposite effect. The effect varied with the barley accessions. The current study is the first attempt in investigating the effect of hormones on metabolite profiles in germinating barley grain, being helpful for identifying the factors affecting barley germination or malt quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Metabolite changes during the life history of Porphyra haitanensis.

    Science.gov (United States)

    Wang, X; Zhao, P; Luo, Q; Yan, X; Xu, J; Chen, J; Chen, H

    2015-05-01

    Plant metabolomics is essentially the comprehensive analysis of complex metabolites of plant extracts. Metabolic fingerprinting is an important part of plant metabolomics research. In this study, metabolic fingerprinting of different stages of the life history of the red alga Porphyra haitanensis was performed. The stages included conchocelis filaments, sporangial branchlets, conchosporangia, discharged conchospores and conchosporangial branchlets after conchospore discharge. Metabolite extracts were analysed with ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole-time of flight mass spectrometry. Analyses profiles were subjected to principal components analysis and orthogonal projection to latent structures discriminant analysis using the SIMCA-P software for biomarker selection and identification. Based on the MS/MS spectra and data from the literature, potential biomarkers, mainly of phosphatidylcholine and lysophosphatidylcholine, were identified. Identification of these biomarkers suggested that plasma membrane phospholipids underwent major changes during the life history of P. haitanensis. The levels of phosphatidylcholine and lysophosphatidylcholine increased in sporangial branchlets and decreased in discharged conchospores. Moreover, levels of sphingaine (d18:0) decreased in sporangial branchlets and increased in discharged conchospores, which indicates that membrane lipids were increasingly synthesised as energy storage in sporangial branchlets, while energy was consumed in sporangial branchlets to discharged conchospores. A metabolomic study of different growth phases of P. haitanensis will enhance our understanding of its physiology and ecology. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

    Science.gov (United States)

    Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

    2017-06-01

    Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

    Science.gov (United States)

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-04-20

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

  7. Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility

    Science.gov (United States)

    Yang, Yi; Park, So-Yeon; Nguyen, Thanh Thi; Yu, Young Hyun; Nguyen, Tru Van; Sun, Eun Gene; Udeni, Jayalal; Jeong, Min-Hye; Pereira, Iris; Moon, Cheol; Ha, Hyung-Ho; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2015-01-01

    Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3’-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action. PMID:26371759

  8. Production of Phytotoxic Metabolite Using Biphasic Fermentation System from Strain C1136 of Lasiodiplodia pseudotheobromae, a Potential Bioherbicidal Agent

    Directory of Open Access Journals (Sweden)

    Charles Oluwaseun ADETUNJI

    2017-09-01

    Full Text Available Formulation of effective and environmental friendly bioherbicides depends on the type of fermentation medium used for the production of phytotoxic metabolites. The effect of biomass, colony forming unit and the phytotoxic metabolite produced from the biphasic fermentation was carried out, while the phytotoxic metabolite was tested in vivo and in-vitro on Echinochola crus-galli and dicotyledonous Chromolaena odorata. The mutant strain of Lasiodiplodia pseudotheobromae C1136 (Lp90 produced the highest amount of conidia and the largest necrotic area on the two tested weeds when compared to its wild strain in the different biphasic media combinations. The study revealed that the biphasic system containing PDB + rice produced the highest bioherbicidal activities. Therefore, the phytotoxic metabolites from strain C1136 are suggested for large scale production of bioherbicides for the management of weeds in conventional farming to improve yield and enhance food security.

  9. Antibacterial activity of secondary metabolites isolated from ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... The aims of this study were the analysis of the secondary metabolites and evaluation of the antibacterial and antifungal activity of Alternaria alternata. Twenty six bioactive compounds were identified in methanolic extract of Alternaria alternata. The identification of bioactive chemical compounds is based on ...

  10. Anticancer and antibacterial secondary metabolites from the ...

    African Journals Online (AJOL)

    Background: The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. Objectives: This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., ...

  11. Chemical composition, secondary metabolites, in vitro gas ...

    African Journals Online (AJOL)

    Chemical composition, secondary metabolites, in vitro gas production characteristics and acceptability study of some forage for ruminant feeding in South-Western Nigeria. ... Chemical composition and qualitative analysis of saponins, phenol and steroids of the plants were determined. In vitro gas production (IVGP) was ...

  12. Homeorhetic hormones, metabolites and accelerated growth

    African Journals Online (AJOL)

    Homeorhetic hormones, metabolites and accelerated growth. A.L. Marais and J.G. van der Walt. Rumen Biochemistry, Animal and Dairy Science Research Institute,. Irene 1675, Republic of South Africa. Six newly weaned karakul ewes, three with fat tails and three without tails, were used to investigate the metabolic and hor ...

  13. Organic metabolites produced by Vibrio parahaemolyticus strain ...

    African Journals Online (AJOL)

    Identification and action of several antibacterial metabolites produced by a fish pathogen Vibrio parahaemolyticus strain An3 from marine ecosystem of Goa has been demonstrated. Antibacterial activity of the crude cell extract of the test bacterium has been evaluated against indicator pathogenic bacterial strains such as ...

  14. Secondary metabolites from Scorzonera latifolia roots

    Czech Academy of Sciences Publication Activity Database

    Acikara, O. B.; Šmejkal, K.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Saltan, G.

    2015-01-01

    Roč. 81, č. 16 (2015), PM167 ISSN 0032-0943. [GA 2015. International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research /63./. 23.08.2015-27.08.2015, Budapest] Institutional support: RVO:61388963 Keywords : medical plant * metabolites * Asteraceae Subject RIV: CB - Analytical Chemistry, Separation

  15. Antibacterial activity of secondary metabolites isolated from ...

    African Journals Online (AJOL)

    The aims of this study were the analysis of the secondary metabolites and evaluation of the antibacterial and antifungal activity of Alternaria alternata. Twenty six bioactive compounds were identified in methanolic extract of Alternaria alternata. The identification of bioactive chemical compounds is based on the peak area, ...

  16. Blood metabolite concentrations and postpartum resumption of ...

    African Journals Online (AJOL)

    Fred

    2014-01-29

    Jan 29, 2014 ... Abstract. An experiment was conducted to investigate the effect of concentrations of certain blood nutrient- sensitive metabolites and the resumption of postpartum ovarian cyclicity in 16 Sanga cows (mean BCS 5). Blood samples were taken from cows from weeks 1 to 13 (90 days) postpartum, processed ...

  17. Flagella-Driven Flows Circumvent Diffusive Bottlenecks that Inhibit Metabolite Exchange

    Science.gov (United States)

    Short, Martin; Solari, Cristian; Ganguly, Sujoy; Kessler, John; Goldstein, Raymond; Powers, Thomas

    2006-03-01

    The evolution of single cells to large and multicellular organisms requires matching the organisms' needs to the rate of exchange of metabolites with the environment. This logistic problem can be a severe constraint on development. For organisms with a body plan that approximates a spherical shell, such as colonies of the volvocine green algae, the required current of metabolites grows quadratically with colony radius whereas the rate at which diffusion can exchange metabolites grows only linearly with radius. Hence, there is a bottleneck radius beyond which the diffusive current cannot keep up with metabolic demands. Using Volvox carteri as a model organism, we examine experimentally and theoretically the role that advection of fluid by surface-mounted flagella plays in enhancing nutrient uptake. We show that fluid flow driven by the coordinated beating of flagella produces a convective boundary layer in the concentration of a diffusing solute which in turn renders the metabolite exchange rate quadratic in the colony radius. This enhanced transport circumvents the diffusive bottleneck, allowing increase in size and thus evolutionary transitions to multicellularity in the Volvocales.

  18. Molluscicidal metabolites from an assemblage of Palmyra Atoll cyanobacteria.

    Science.gov (United States)

    Pereira, Alban R; Etzbach, Lena; Engene, Niclas; Müller, Rolf; Gerwick, William H

    2011-05-27

    Molluscicides can play an important role in the control of schistosomiasis because snails of the genus Biomphalaria act as intermediate hosts for the parasite. Schistosomiasis is one of 13 neglected tropical diseases with high morbidity and mortality that collectively affect one billion of the world's poorest population, mainly in developing countries. Thiopalmyrone (1) and palmyrrolinone (2), metabolites isolated from extracts of a Palmyra Atoll environmental assemblage of two cyanobacteria, cf. Oscillatoria and Hormoscilla spp., represent new and potent molluscicidal chemotypes against Biomphalaria glabrata (LC50=8.3 and 6.0 μM, respectively). A slight enhancement in molluscicidal effect (LC50=5.0 μM) was observed when these two natural products were utilized as an equimolar binary mixture.

  19. An update on organohalogen metabolites produced by basidiomycetes

    NARCIS (Netherlands)

    Field, J.A.; Wijnberg, J.B.P.A.

    2003-01-01

    Basidiomycetes are an ecologically important group of higher fungi known for their widespread capacity to produce organohalogen metabolites. To date, 100 different organohalogen metabolites (mostly chlorinated) have been identified from strains in 70 genera of Basidiomycetes. This manuscript

  20. Discovering the secondary metabolite potential encoded within entomopathogenic fungi.

    Science.gov (United States)

    Gibson, Donna M; Donzelli, Bruno G G; Krasnoff, Stuart B; Keyhani, Nemat O

    2014-10-01

    This highlight discusses the secondary metabolite potential of the insect pathogens Metarhizium and Beauveria, including a bioinformatics analysis of secondary metabolite genes for which no products are yet identified.

  1. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Science.gov (United States)

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  2. Metabolite Depletion Affects Flux Profiling of Cell Lines

    DEFF Research Database (Denmark)

    Nilsson, A.; Haanstra, J. R.; Teusink, B.

    2018-01-01

    Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.......Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation....

  3. SPE-NMR metabolite sub-profiling of urine

    NARCIS (Netherlands)

    Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

    2012-01-01

    NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has

  4. Identifying diseases-related metabolites using random walk.

    Science.gov (United States)

    Hu, Yang; Zhao, Tianyi; Zhang, Ningyi; Zang, Tianyi; Zhang, Jun; Cheng, Liang

    2018-04-11

    Metabolites disrupted by abnormal state of human body are deemed as the effect of diseases. In comparison with the cause of diseases like genes, these markers are easier to be captured for the prevention and diagnosis of metabolic diseases. Currently, a large number of metabolic markers of diseases need to be explored, which drive us to do this work. The existing metabolite-disease associations were extracted from Human Metabolome Database (HMDB) using a text mining tool NCBO annotator as priori knowledge. Next we calculated the similarity of a pair-wise metabolites based on the similarity of disease sets of them. Then, all the similarities of metabolite pairs were utilized for constructing a weighted metabolite association network (WMAN). Subsequently, the network was utilized for predicting novel metabolic markers of diseases using random walk. Totally, 604 metabolites and 228 diseases were extracted from HMDB. From 604 metabolites, 453 metabolites are selected to construct the WMAN, where each metabolite is deemed as a node, and the similarity of two metabolites as the weight of the edge linking them. The performance of the network is validated using the leave one out method. As a result, the high area under the receiver operating characteristic curve (AUC) (0.7048) is achieved. The further case studies for identifying novel metabolites of diabetes mellitus were validated in the recent studies. In this paper, we presented a novel method for prioritizing metabolite-disease pairs. The superior performance validates its reliability for exploring novel metabolic markers of diseases.

  5. Antibacterial secondary metabolites from the cave sponge Xestospongia sp.

    Science.gov (United States)

    Ankisetty, Sridevi; Slattery, Marc

    2012-05-01

    Chemical investigation of the cave sponge Xestospongia sp. resulted in the isolation of three new polyacetylenic long chain compounds along with two known metabolites. The structures of the new metabolites were established by NMR and MS analyses. The antibacterial activity of the new metabolites was also evaluated.

  6. Antibacterial Secondary Metabolites from the Cave Sponge Xestospongia sp

    OpenAIRE

    Ankisetty, Sridevi; Slattery, Marc

    2012-01-01

    Chemical investigation of the cave sponge Xestospongia sp. resulted in the isolation of three new polyacetylenic long chain compounds along with two known metabolites. The structures of the new metabolites were established by NMR and MS analyses. The antibacterial activity of the new metabolites was also evaluated.

  7. Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia

    Directory of Open Access Journals (Sweden)

    Julia Kuligowski

    2017-08-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6 h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia. The metabolite score's performance as a biomarker for perinatal hypoxia and its usefulness for clinical grading and decision making have been assessed and compared to the performance of lactate which is currently considered the gold standard. For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate. However, it provided an enhanced predictive capacity at 2 h after resuscitation. The present study evidences the usefulness of the metabolite score for improving the early assessment of the severity of the hypoxic insult based on serial determinations in a minimally invasive biofluid. The applicability of the metabolite score for clinical diagnosis and patient stratification for hypothermia treatment has to be confirmed in multicenter trials involving newborns suffering from HIE. Keywords: Hypoxia, Perinatal asphyxia, Newborn, Metabolic biomarker, Neonatal piglet model, Liquid Chromatography – Time-of-Flight Mass Spectrometry (LC-TOF-MS

  8. Identifying metabolites related to nitrogen mineralisation using 1H NMR spectroscopy

    Science.gov (United States)

    . T McDonald, Noeleen; Graham, Stewart; Watson, Catherine; Gordon, Alan; Lalor, Stan; Laughlin, Ronnie; Elliott, Chris; . P Wall, David

    2015-04-01

    Exploring new analysis techniques to enhance our knowledge of the various metabolites within our soil systems is imperative. Principally, this knowledge would allow us to link key metabolites with functional influences on critical nutrient processes, such as the nitrogen (N) mineralisation in soils. Currently there are few studies that utilize proton nuclear magnetic resonance spectroscopy (1H NMR) to characterize multiple metabolites within a soil sample. The aim of this research study was to examine the effectiveness of 1H NMR for isolating multiple metabolites that are related to the mineralizable N (MN) capacity across a range of 35 Irish grassland soils. Soils were measured for MN using the standard seven day anaerobic incubation (AI-7). Additionally, soils were also analysed for a range of physio-chemical properties [e.g. total N, total C, mineral N, texture and soil organic matter (SOM)]. Proton NMR analysis was carried on these soils by extracting with 40% methanol:water, lyophilizing and reconstituting in deuterium oxide and recording the NMR spectra on a 400MHz Bruker AVANCE III spectrometer. Once the NMR data were spectrally processed and analysed using multivariate statistical analysis, seven metabolites were identified as having significant relationships with MN (glucose, trimethylamine, glutamic acid, serine, aspartic acid, 4-aminohippuirc acid and citric acid). Following quantification, glucose was shown to explain the largest percentage variability in MN (72%). These outcomes suggest that sources of labile carbon are essential in regulating N mineralisation and the capacity of plant available N derived from SOM-N pools in these soils. Although, smaller in concentration, the amino acids; 4-aminohippuirc acid, glutamic acid and serine also significantly (P<0.05) explained 43%, 27% and 19% of the variability in MN, respectively. This novel study highlights the effectiveness of using 1H NMR as a practical approach to profile multiple metabolites in

  9. Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

    NARCIS (Netherlands)

    Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

    2013-01-01

    Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

  10. Biologically Active Metabolites Synthesized by Microalgae

    Directory of Open Access Journals (Sweden)

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  11. Biologically Active Metabolites Synthesized by Microalgae.

    Science.gov (United States)

    de Morais, Michele Greque; Vaz, Bruna da Silva; de Morais, Etiele Greque; Costa, Jorge Alberto Vieira

    2015-01-01

    Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  12. Metabolite production by differnt Ulocladium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Hollensted, Morten

    2008-01-01

    Ulocladium, which is phylogenetically related to Alternaria, contains species that are food spoilers and plant pathogens, but also species that have potential as enzyme producers and bio-control agents. Ulocladium spp. are often found on dead vegetation, in soil, air and dust, but also on food...... metabolites was correlated to species identity and source of isolation (substratum). Chemical analyses corroborated the morphological identifications and showed the existence of several species species-specific metabolites, of which most were known Compounds. The production of curvularins was specific...... to Ulocladium atrum, while most species produced infectopyrones and derivatives of altertoxin I. None of the 52 Ulocladium strains produced alternariols, tenuazonic acid, altersolanols or macrosporin, which are common in species of Alternaria. (c) 2008 Elsevier B.V. All rights reserved...

  13. Vitamin D metabolites in human milk

    International Nuclear Information System (INIS)

    Weisman, Y.; Bawnik, J.C.; Eisenberg, Z.; Spirer, Z.

    1982-01-01

    The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk

  14. The neurotoxicity of pyridinium metabolites of haloperidol

    Directory of Open Access Journals (Sweden)

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  15. Biologically Active Metabolites Synthesized by Microalgae

    Science.gov (United States)

    Costa, Jorge Alberto Vieira

    2015-01-01

    Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

  16. Role of metabolites of cyclophosphamide in cardiotoxicity

    OpenAIRE

    Kurauchi, Koichiro; Nishikawa, Takuro; Miyahara, Emiko; Okamoto, Yasuhiro; Kawano, Yoshifumi

    2017-01-01

    Background The dose-limiting toxic effect of cyclophosphamide (CY) is cardiotoxicity. The pathogenesis of myocardial damage is poorly understood, and there is no established means of prevention. In previous studies, we suggested that for CY-induced cardiotoxicity, whereas acrolein is the key toxic metabolite, carboxyethylphosphoramide mustard (CEPM) is protective. We sought to verify that acrolein is the main cause of cardiotoxicity and to investigate whether aldehyde dehydrogenase (ALDH), wh...

  17. Research for the lichen Usnea barbata metabolites.

    Science.gov (United States)

    Bazarnova, Yulia; Politaeva, Natalia; Lyskova, Nadegda

    2018-03-29

    This work presents investigations of biologically active metabolites of Usnea barbata lichen. Extraction conditions for usnic acid and other biologically active phytocomponents using various solvent systems were chosen. Modern analytical techniques were used to study composition of the obtained extracts; usnic acid and phenolic compound contents were estimated. Antioxidant activity and antimicrobial properties of lichen dry extract against bacteria Bacillus subtilis and Pseudomonas fluorescens were studied.

  18. Transfer of metabolites across the peroxisomal membrane.

    Science.gov (United States)

    Antonenkov, Vasily D; Hiltunen, J Kalervo

    2012-09-01

    Peroxisomes perform a large variety of metabolic functions that require a constant flow of metabolites across the membranes of these organelles. Over the last few years it has become clear that the transport machinery of the peroxisomal membrane is a unique biological entity since it includes nonselective channels conducting small solutes side by side with transporters for 'bulky' solutes such as ATP. Electrophysiological experiments revealed several channel-forming activities in preparations of plant, mammalian, and yeast peroxisomes and in glycosomes of Trypanosoma brucei. The properties of the first discovered peroxisomal membrane channel - mammalian Pxmp2 protein - have also been characterized. The channels are apparently involved in the formation of peroxisomal shuttle systems and in the transmembrane transfer of various water-soluble metabolites including products of peroxisomal β-oxidation. These products are processed by a large set of peroxisomal enzymes including carnitine acyltransferases, enzymes involved in the synthesis of ketone bodies, thioesterases, and others. This review discusses recent data pertaining to solute permeability and metabolite transport systems in peroxisomal membranes and also addresses mechanisms responsible for the transfer of ATP and cofactors such as an ATP transporter and nudix hydrolases. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Phthalate Metabolites, Consumer Habits and Health Effects

    Directory of Open Access Journals (Sweden)

    Peter Wallner

    2016-07-01

    Full Text Available Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP, mono-n-butyl phthalate (MnBP, mono-isobutyl phthalate (MiBP, monobenzyl phthalate (MBzP, mono-(2-ethylhexyl phthalate (MEHP, mono-(2-ethyl-5-hydroxyhexyl phthalate (5OH-MEHP, mono-(2-ethyl-5-oxohexyl phthalate (5oxo-MEHP, mono-(5-carboxy-2-ethylpentyl phthalate (5cx-MEPP, and 3-carboxy-mono-propyl phthalate (3cx-MPP could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET bottles and the diethyl phthalate (DEP metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  20. Nontargeted Identification of Reactive Metabolite Protein Adducts.

    Science.gov (United States)

    Leeming, Michael G; Donald, William A; O'Hair, Richard A J

    2017-06-06

    Metabolic bioactivation of many different chemicals results in the formation of highly reactive compounds (chemically reactive metabolites, CRMs) that can lead to toxicity via binding to macromolecular targets (e.g., proteins or DNA). There is a need to develop robust, rapid, and nontargeted analytical techniques to determine the identity of the protein targets of CRMs and their sites of modification. Here, we introduce a nontargeted methodology capable of determining both the identity of a CRM formed from an administered compound as well as the protein targets modified by the reactive metabolite in a single experiment without prior information. Acetaminophen (N-acetyl-p-aminophenol, APAP) and 13 C 6 -APAP were incubated with rat liver microsomes, which are known to bioactivate APAP to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). Global tryptic digestion followed by liquid chromatographic/mass spectrometric (LC/MS) analysis was used to locate "twin" ion peaks of peptides adducted by NAPQI and for shotgun proteomics via tandem mass spectrometry (MS/MS). By the development of blended data analytics software called Xenophile, the identity of the amino acid residue that was adducted can be established, which eliminates the need for specific parametrization of protein database search algorithms. This combination of experimental design and data analysis software allows the identity of a CRM, the protein target, and the amino acid residues that are modified to be rapidly established directly from experimental data. Xenophile is freely available from https://github.com/mgleeming/Xenophile .

  1. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Science.gov (United States)

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  2. The WEIZMASS spectral library for high-confidence metabolite identification.

    Science.gov (United States)

    Shahaf, Nir; Rogachev, Ilana; Heinig, Uwe; Meir, Sagit; Malitsky, Sergey; Battat, Maor; Wyner, Hilary; Zheng, Shuning; Wehrens, Ron; Aharoni, Asaph

    2016-08-30

    Annotation of metabolites is an essential, yet problematic, aspect of mass spectrometry (MS)-based metabolomics assays. The current repertoire of definitive annotations of metabolite spectra in public MS databases is limited and suffers from lack of chemical and taxonomic diversity. Furthermore, the heterogeneity of the data prevents the development of universally applicable metabolite annotation tools. Here we present a combined experimental and computational platform to advance this key issue in metabolomics. WEIZMASS is a unique reference metabolite spectral library developed from high-resolution MS data acquired from a structurally diverse set of 3,540 plant metabolites. We also present MatchWeiz, a multi-module strategy using a probabilistic approach to match library and experimental data. This strategy allows efficient and high-confidence identification of dozens of metabolites in model and exotic plants, including metabolites not previously reported in plants or found in few plant species to date.

  3. Comparison of hesperetin and its metabolites for cholesterol-lowering and antioxidative efficacy in hypercholesterolemic hamsters.

    Science.gov (United States)

    Kim, Hye-Jin; Jeon, Seon-Min; Lee, Mi-Kyung; Cho, Yun-Young; Kwon, Eun-Young; Lee, Jin Hee; Choi, Myung-Sook

    2010-08-01

    This study was performed to compare the hypolipidemic and antioxidant efficacy of hesperetin and its metabolites in hypercholesterolemic hamsters. The hamsters were fed a high-fat (10% coconut oil and 0.2% cholesterol, wt/wt) diet or a high-fat diet supplemented with hesperetin (0.02%) or hesperetin metabolites, 3,4-dihydroxyphenylpropionic acid (DHPP) (0.012%) and 3-methoxy-4-hydroxycinnamic acid (ferulic acid) (0.013%), for 12 weeks. Dietary DHPP and ferulic acid were found to have significantly decreased the levels of the plasma total cholesterol, non-high-density lipoprotein-cholesterol (HDL-C), apolipoprotein B, hepatic lipids, and cholesterol-regulating enzymes compared to the control group. In particular, ferulic acid was more potent with respect to raising HDL-C/total cholesterol ratio and paraoxonase levels while decreasing atherogenic index values. Hesperetin and its metabolites seemed to enhance antioxidant capacity by lowering the hydrogen peroxide and lipid peroxide (thiobarbituric acid-reactive substrates) levels. Among the hesperetin metabolites tested, the relative potency of ferulic acid for reducing the risks of atherosclerosis in hamsters was found to be greater.

  4. Ultrahigh Pressure Processing Produces Alterations in the Metabolite Profiles of Panax ginseng.

    Science.gov (United States)

    Lee, Mee Youn; Singh, Digar; Kim, Sung Han; Lee, Sang Jun; Lee, Choong Hwan

    2016-06-22

    Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG; UHP-treated RG: URG; ginseng berries: GB; and UHP-treated GB: UGB) using metabolite profiling based on ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Multivariate data analyses revealed a clear demarcation among the GB and UGB samples, and the phenotypic evaluations correlated the highest antioxidant activities and the total phenolic and flavonoid compositions with the UGB samples. Overall, eight amino acids, seven organic acids, seven sugars and sugar derivatives, two fatty acids, three notoginsenosides, three malonylginsenosides, and three ginsenosides, were identified as significantly discriminant metabolites between the GB and UGB samples, with relatively higher proportions in the latter. Ideally, these metabolites can be used as quality biomarkers for the assessment of ginseng products and our results indicate that UHP treatment likely led to an elevation in the proportions of total extractable metabolites in ginseng samples.

  5. Endophytes as in vitro production platforms of high value plant secondary metabolites.

    Science.gov (United States)

    Venugopalan, Aarthi; Srivastava, Smita

    2015-11-01

    Many reports have been published on bioprospecting of endophytic fungi capable of producing high value bioactive molecules like, paclitaxel, vincristine, vinblastine, camptothecin and podophyllotoxin. However, commercial exploitation of endophytes for high value-low volume plant secondary metabolites remains elusive due to widely reported genomic instability of endophytes in the axenic culture. While most of the endophyte research focuses on screening endophytes for novel or existing high value biomolecules, very few reports seek to explore the possible mechanisms of production of host-plant associated or novel secondary metabolites in these organisms. With an overview of host-endophyte relationship and its possible impact on the secondary metabolite production potential of endophytes, the review highlights the evidence reported for and against the presence of host-independent biosynthetic machinery in endophytes. The review aims to address the question, why should and how can endophytes be exploited for large scale in vitro production of high value phytochemicals? In this regard, various bioprocess optimization strategies that have been applied to sustain and enhance the product yield from the endophytes have also been described in detail. Further, techniques like mixed fermentation/co-cultivation and use of epigenetic modifiers have also been discussed as potential strategies to activate cryptic gene clusters in endophytes, thereby aiding in novel metabolite discovery and overcoming the limitations associated with axenic culture of endophytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Radiation-induced mutagenesis of antifungal metabolite producing bacillus sp. HKA-17

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Keun; Senthilkumar, M. [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-09-15

    Bacillus sp. Strain HKA-17, isolated from the surface sterilized root nodule of Glycine max, inhibited several fungal plant pathogens. It produced a diffusible extracellular antifungal metabolite that was extracted with n-butanol. The crude extract was purified through Superdex{sup TM} 75 10/300 GL FPLC column. FT-IR spectrum of the FPLC purified-antifungal metabolite confirmed the presence of peptide and glycosidic bonds in its structure. Gamma induced mutagenesis of HKA-17 was carried out at an LD{sub 99} dose (8.46 kGy) to generate a mutant library. By screening the mutant library through a duel plate assay with Alternaria alternata, we selected one mutant with enhanced biocontrol activity (HKA-17e1) and two defective mutants (HKA-17d1 and HKA-17d2). Overproducing mutant recorded the largest inhibition zone (16.25 {+-} 0.86 mm) compared to any other mutant clone as well as wild type, and could be used as a potential biocontrol agent for plant disease suppression. The effect of HKA-17 antifungal metabolite on hyphal morphology was clearly demonstrated through scanning electron microscopy. The crude extract of defective mutant HKA-17 d1 did not induce any changes in hyphal morphology of A. alternata. However, antifungal metabolites of HKA-17 induced abnormal hyphal structures such as hyphal shrivelling, the bulging and swelling of intercalary cells, fragmentation, and cell lysis.

  7. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

    Science.gov (United States)

    Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

    2013-01-01

    The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

  8. Trophic transfer of pyrene metabolites between aquatic invertebrates

    International Nuclear Information System (INIS)

    Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

    2013-01-01

    The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

  9. Metabolite damage and repair in metabolic engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

  10. Endogenous cross-talk of fungal metabolites.

    Directory of Open Access Journals (Sweden)

    Kevin J Sheridan

    2015-01-01

    Full Text Available Non-ribosomal peptide synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent non-ribosomal peptide via a thiotemplate mechanism catalysed by non-ribosomal peptide synthetases. Substrate amino acids can be modified prior to or during incorporation into the non-ribosomal peptide, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases and glutathione transferases which are essential to effect biosynthesis of the final non-ribosomal peptide. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancilliary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: CoA, acetyl CoA, S-adenosylmethionine, glutathione, NADPH, malonyl CoA and molecular oxygen, amongst others are required for non-ribosomal peptide and polyketide synthesis. Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of non-ribosomal peptides, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids, along with localization to similar regions within fungi (e.g., conidia suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in non-ribosomal peptide and polyketide synthesis play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite.

  11. Cytotoxicity of lapachol metabolites produced by probiotics.

    Science.gov (United States)

    Oliveira Silva, E; Cruz de Carvalho, T; Parshikov, I A; Alves dos Santos, R; Silva Emery, F; Jacometti Cardoso Furtado, N A

    2014-07-01

    Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9β-hexahydroindeno[1,2-β]pyran-9β-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 μmol l(-1) ) than lapachol (IC50 = 72.3 μmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 μmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess

  12. [Identification of saponins from Panax notoginseng in metabolites of rats].

    Science.gov (United States)

    Shen, Wen-Wen; Zhang, Yin; Qiu, Shou-Bei; Zhu, Fen-Xia; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

    2017-10-01

    UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified. Copyright© by the Chinese Pharmaceutical Association.

  13. Activation of the reticulothalamic cholinergic pathway by the major metabolites of aniracetam.

    Science.gov (United States)

    Nakamura, K; Shirane, M

    1999-09-10

    The aim of the study was to further investigate the effects of aniracetam, a cognition enhancer, and its metabolites on the brain cholinergic system. We measured choline acetyltransferase activity and acetylcholine release using in vivo brain microdialysis in stroke-prone spontaneously hypertensive rats (SHRSP). The enzyme activity in the pons-midbrain and hippocampus, and basal acetylcholine release in the nucleus reticularis thalami were lower in SHRSP than in age-matched Wistar Kyoto rats, indicating central cholinergic deficits in SHRSP. Repeated treatment of aniracetam (50 mg/kg p.o. x 11 for 6 days) preferentially increased the enzyme activity in the thalamus, whereas decreased it in the striatum. Among the metabolites of aniracetam, local perfusion of N-anisoyl-gamma-aminobutyric acid (GABA, 0.1 and/or 1 microM) and p-anisic acid (1 microM) into the nucleus reticularis thalami, dorsal hippocampus and prefrontal cortex of SHRSP produced a significant but delayed increase of acetylcholine release. We failed, however, to find any effect of aniracetam itself. A direct injection of N-anisoyl-GABA (1 nmol) into the pedunculopontine tegmental nucleus of SHRSP enhanced the release in the nucleus reticularis thalami. Thus, these data prove that aniracetam can facilitate central cholinergic neurotransmission via both metabolites. Based on its pharmacokinetic profile, N-anisoyl-GABA may contribute to the clinical effects of aniracetam, mainly by acting on the reticulothalamic cholinergic pathway.

  14. Structural elucidation of major selective androgen receptor modulator (SARM) metabolites for doping control.

    Science.gov (United States)

    Garg, Neeraj; Hansson, Annelie; Knych, Heather K; Stanley, Scott D; Thevis, Mario; Bondesson, Ulf; Hedeland, Mikael; Globisch, Daniel

    2018-01-31

    Selective androgen receptor modulators (SARMs) are a class of androgen receptor drugs, which have a high potential to be performance enhancers in human and animal sports. Arylpropionamides are one of the major SARM classes and get rapidly metabolized significantly complicating simple detection of misconduct in blood or urine sample analysis. Specific drug-derived metabolites are required as references due to a short half-life of the parent compound but are generally lacking. The difficulty in metabolism studies is the determination of the correct regio and stereoselectivity during metabolic conversion processes. In this study, we have elucidated and verified the chemical structure of two major equine arylpropionamide-based SARM metabolites using a combination of chemical synthesis and liquid chromatography-mass spectrometry (LC-MS) analysis. These synthesized SARM-derived metabolites can readily be utilized as reference standards for routine mass spectrometry-based doping control analysis of at least three commonly used performance-enhancing drugs to unambigously identify misconduct.

  15. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

    Directory of Open Access Journals (Sweden)

    Sissel J. Moltu

    2014-05-01

    Full Text Available Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate. The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

  16. Metabolite Profiling of Peppers of Various Colors Reveals Relationships Between Tocopherol, Carotenoid, and Phytosterol Content.

    Science.gov (United States)

    Kim, Tae Jin; Choi, Jaehyuk; Kim, Kil Won; Ahn, Soon Kil; Ha, Sun-Hwa; Choi, Yongsoo; Park, Nam Il; Kim, Jae Kwang

    2017-12-01

    Peppers are widely consumed in Korea; the varietal development of peppers with increased content of beneficial plant metabolites is, therefore, of considerable interest. This requires a comprehensive understanding of the metabolic profile of pepper plants and the factors affecting this profile. To this end, we determined the content of various metabolites, such as hydrophilic and lipophilic compounds, phenolic acids, carotenoids, and capsaicinoids in peppers of various colors (green, red, pale green, and violet peppers) and in a high-pungency (green) pepper. We also performed principal component analysis (PCA), Pearson's correlation analysis, and hierarchical clustering analysis (HCA) to determine the relationships among these metabolites in peppers. PCA results indicated no significant variances among the 3 sample replicates. The HCA showed correlations between the metabolites resulting from common or closely linked biosynthesis pathways. Our results showed that carotenoids correlated positively with tocopherols and negatively with phytosterols; our findings also indicated a close relationship between the methylerythritol 4-phosphate and mevalonic acid biosynthesis pathways, providing evidence in favor of an earlier hypothesis regarding crosstalk across the chloroplast membrane. We, thus, demonstrate that metabolic profiling combined with multivariate analysis is a useful tool for analyzing metabolic networks. A total of 71 metabolites were measured in 5 peppers of different colors. The metabolic profiling with multivariate analysis revealed that tocopherol content had a positive correlation with the carotenoid content and a negative correlation with the phytosterol content. The results of this study may help in breeding programs to produce new germplasm with enhanced nutritional quality. © 2017 Institute of Food Technologists®.

  17. Exploring plant tissue culture in Withania somnifera (L.) Dunal: in vitro propagation and secondary metabolite production.

    Science.gov (United States)

    Shasmita; Rai, Manoj K; Naik, Soumendra K

    2017-12-26

    Withania somnifera (L.) Dunal (family: Solanaceae), commonly known as "Indian Ginseng", is a medicinally and industrially important plant of the Indian subcontinent and other warmer parts of the world. The plant has multi-use medicinal potential and has been listed among 36 important cultivated medicinal plants of India that are in high demand for trade due to its pharmaceutical uses. The medicinal importance of this plant is mainly due to the presence of different types of steroidal lactones- withanolides in the roots and leaves. Owing to low seed viability and poor germination, the conventional propagation of W. somnifera falls short to cater its commercial demands particularly for secondary metabolite production. Therefore, there is a great need to develop different biotechnological approaches through tissue and organ culture for seasonal independent production of plants in large scale which will provide sufficient raw materials of uniform quality for pharmaceutical purposes. During past years, a number of in vitro plant regeneration protocols via organogenesis and somatic embryogenesis and in vitro conservation through synthetic seed based encapsulation technology have been developed for W. somnifera. Several attempts have also been made to standardize the protocol of secondary metabolite production via tissue/organ cultures, cell suspension cultures, and Agrobacterium rhizogenes-mediated transformed hairy root cultures. Employment of plant tissue culture based techniques would provide means for rapid propagation and conservation of this plant species and also provide scope for enhanced production of different bioactive secondary metabolites. The present review provides a comprehensive report on research activities conducted in the area of tissue culture and secondary metabolite production in W. somnifera during the past years. It also discusses the unexplored areas which might be taken into consideration for future research so that the medicinal properties and

  18. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    OpenAIRE

    Valentin Bhimba B; V Vinod; M Cindhu Beulah

    2011-01-01

    Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra) collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites...

  19. Differences between human plasma and serum metabolite profiles.

    Directory of Open Access Journals (Sweden)

    Zhonghao Yu

    Full Text Available BACKGROUND: Human plasma and serum are widely used matrices in clinical and biological studies. However, different collecting procedures and the coagulation cascade influence concentrations of both proteins and metabolites in these matrices. The effects on metabolite concentration profiles have not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the concentrations of 163 metabolites in plasma and serum samples collected simultaneously from 377 fasting individuals. To ensure data quality, 41 metabolites with low measurement stability were excluded from further analysis. In addition, plasma and corresponding serum samples from 83 individuals were re-measured in the same plates and mean correlation coefficients (r of all metabolites between the duplicates were 0.83 and 0.80 in plasma and serum, respectively, indicating significantly better stability of plasma compared to serum (p = 0.01. Metabolite profiles from plasma and serum were clearly distinct with 104 metabolites showing significantly higher concentrations in serum. In particular, 9 metabolites showed relative concentration differences larger than 20%. Despite differences in absolute concentration between the two matrices, for most metabolites the overall correlation was high (mean r = 0.81±0.10, which reflects a proportional change in concentration. Furthermore, when two groups of individuals with different phenotypes were compared with each other using both matrices, more metabolites with significantly different concentrations could be identified in serum than in plasma. For example, when 51 type 2 diabetes (T2D patients were compared with 326 non-T2D individuals, 15 more significantly different metabolites were found in serum, in addition to the 25 common to both matrices. CONCLUSIONS/SIGNIFICANCE: Our study shows that reproducibility was good in both plasma and serum, and better in plasma. Furthermore, as long as the same blood preparation procedure is

  20. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...... supplementation. The other pyrazine metabolites, all related pyrazines with either one, two or three alkyl substituents, were identified by means of their mass spectral data and/or co-elution with authentic standards....

  1. Secondary metabolites in grasses: characterization and biological activity

    OpenAIRE

    Aldo Tava

    2007-01-01

    In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers), but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to th...

  2. Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

    OpenAIRE

    Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

    2007-01-01

    The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydro...

  3. Cyanobacteria as Cell Factories to Produce Plant Secondary Metabolites

    OpenAIRE

    Xue, Yong; He, Qingfang

    2015-01-01

    Cyanobacteria represent a promising platform for the production of plant secondary metabolites. Their capacity to express plant P450 proteins, which have essential functions in the biosynthesis of many plant secondary metabolites, makes cyanobacteria ideal for this purpose, and their photosynthetic capability allows cyanobacteria to grow with simple nutrient inputs. This review summarizes the advantages of using cyanobacteria to transgenically produce plant secondary metabolites. Some techniq...

  4. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  5. Exometabolomic Analysis of Cross-Feeding Metabolites.

    Science.gov (United States)

    Lubbe, Andrea; Bowen, Benjamin P; Northen, Trent

    2017-10-04

    Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  6. Exometabolomic Analysis of Cross-Feeding Metabolites

    Directory of Open Access Journals (Sweden)

    Andrea Lubbe

    2017-10-01

    Full Text Available Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  7. Prospective study of blood metabolites associated with colorectal cancer risk.

    Science.gov (United States)

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  8. Possible endocrine disrupting effects of parabens and their metabolites

    DEFF Research Database (Denmark)

    Boberg, Julie; Taxvig, Camilla; Christiansen, Sofie

    2010-01-01

    and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites,little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine...... disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when...

  9. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius

    DEFF Research Database (Denmark)

    Petersen, Lene Maj; Frisvad, Jens Christian; Knudsen, Peter Boldsen

    2015-01-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four...... carbonarins; carbonarins I and J. We have identified the three latter as true sclerotial metabolites. All metabolites were tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin I displayed antifungal activity against Candida albicans, while all four showed antiinsectan activity....... These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites....

  10. Secondary metabolites in grasses: characterization and biological activity

    Directory of Open Access Journals (Sweden)

    Aldo Tava

    2007-12-01

    Full Text Available In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers, but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to their possible pharmacological use. In the present paper studies on secondary metabolites from herbaceous plants are reviewed. Indications of the chemical methods used for their analyses, their presence in the green material and their biological activity are also reported.

  11. Secondary metabolites in grasses: characterization and biological activity

    Directory of Open Access Journals (Sweden)

    Aldo Tava

    2011-02-01

    Full Text Available In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers, but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to their possible pharmacological use. In the present paper studies on secondary metabolites from herbaceous plants are reviewed. Indications of the chemical methods used for their analyses, their presence in the green material and their biological activity are also reported.

  12. How much separation for LC-MS/MS quantitative bioanalysis of drugs and metabolites?

    Science.gov (United States)

    Tan, Aimin; Fanaras, John C

    2018-05-01

    LC-MS/MS has been the dominant analytical technology for quantitative bioanalysis of drugs and metabolites for more than two decades. Despite this, a very fundamental question like how much separation is required for LC-MS/MS quantitative bioanalysis of drugs and metabolites has not been adequately addressed. Some think that no or only very limited separation is necessary thanks to the unparalleled selectivity offered by tandem mass spectrometry. Others think that the more separation, the better, because of the potential detrimental impact of matrix effect (ion suppression or enhancement). Still others just use a rule-of-thumb approach by keeping the adjusted retention/capacity factor always between 2 and 5. The purpose of this article is to address this fundamental question through rational thinking together with various real case examples drawn from regulated bioanalytical laboratories. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Quantitative analysis of sulfur-related metabolites during cadmium stress response in yeast by capillary electrophoresis-mass spectrometry.

    Science.gov (United States)

    Tanaka, Yoshihide; Higashi, Tetsuji; Rakwal, Randeep; Wakida, Shin-ichi; Iwahashi, Hitoshi

    2007-06-28

    The objective of this research is to establish an evaluation system of metabolites by capillary electrophoresis-mass spectrometry (CE-MS) in response to chemical stress using the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C). A method previously reported by Soga et al. was modified and validated for the determination of sulfur-related metabolites, 23 cationic metabolites, in yeast extract. A mixture of 5 mM formic acid in 50% (v/v) 2-propanol was used for the sheath liquid to improve the detection sensitivity. Moreover, washing of CE capillary with 0.1M ammonia solution between successive runs enhanced the reproducibility. After analytical validation, the method was applied to the metabolomic analysis of yeast cells in response to cadmium (Cd) stress. Under Cd exposure, some interesting observations were obtained, particularly the depletion of glycine and the strong accumulation of L-gamma-glutamylcysteine in yeast cells.

  14. Dual labeling of metabolites for metabolome analysis (DLEMMA): A new approach for the identification and relative quantification of metabolites by means of dual isotope labeling and liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Feldberg, Liron; Venger, Ilya; Malitsky, Sergey; Rogachev, Ilana; Aharoni, Asaph

    2009-11-15

    Advanced metabolomics technologies are anticipated to permit the identification and quantification of metabolites at the whole-metabolome scale. Yet, most of the metabolites either remain unknown or cannot be identified unambiguously. Moreover, the present approaches suffer from inaccuracies in relative quantification because of sample preparation and matrix effects. Here we present Dual Labeling of Metabolites for Metabolome Analysis (DLEMMA) as a valuable tool, which with analogy to DNA array assays enables the identification and relative quantification of differential metabolites in a single sample. DLEMMA was demonstrated as an efficient method for reducing the number of possible chemical structures assigned that exhibit the same elemental composition. Its strength was exemplified by the discovery of 10 novel Tryptophan derivatives. Furthermore, employing DLEMMA by feeding two Phenylalanine-labeled precursors, we could detect differential metabolites between transgenic and control plants. The accuracy of relative quantification is also enhanced since DLEMMA provides identical matrixes for both samples, thus avoiding the effects of different complex biological matrixes on electrospray ionization. Hence, DLEMMA will complement and contribute to the advancement of metabolomics technologies and boost metabolic pathway discovery in diverse organisms.

  15. Influence of colour type and previous cultivation on secondary metabolites in hypocotyls and leaves of maca (Lepidium meyenii Walpers).

    Science.gov (United States)

    Clément, Céline; Diaz Grados, Diego A; Avula, Bharathi; Khan, Ihklas A; Mayer, Andrea C; Ponce Aguirre, Dante D; Manrique, Ivan; Kreuzer, Michael

    2010-04-15

    Maca is an Andean crop of the Brassicaceae family which is mainly known for its fertility-enhancing properties following consumption. The hypocotyls display various colours ranging from white to black. Each colour has different biological effects. The aim of this study was to analyse the concentrations of major secondary metabolites in hypocotyls and leaves of maca in a controlled planting experiment in the Peruvian Andes at 4130 m above sea level. The effects of colour type and of previous cultivation of the field were examined. In the hypocotyls, the colour type effect was significant for most secondary metabolites; exceptions were beta-sitosterol and campesterol. The lead-coloured, yellow and violet maca hypocotyls were rich in glucosinolates, macaene and macamides, respectively. Previous cultivation affected macaene, campesterol and indole glucosinolate concentrations. Effects on metabolite concentrations in the leaves were minor. Hypocotyls were richer in macaene, macamides and glucosinolates than were leaves, and were poorer in beta-sitosterol and total phenols. Colour type has to be considered in maca production, as colour associates with variations in concentrations of distinct bioactive metabolites. Leaves may be interesting for animal nutrition purposes as they contain essentially the same secondary metabolites as the hypocotyls but in clearly lower concentrations. (c) 2010 Society of Chemical Industry.

  16. Tiny Microbes with a Big Impact: The Role of Cyanobacteria and Their Metabolites in Shaping Our Future.

    Science.gov (United States)

    Mazard, Sophie; Penesyan, Anahit; Ostrowski, Martin; Paulsen, Ian T; Egan, Suhelen

    2016-05-17

    Cyanobacteria are among the first microorganisms to have inhabited the Earth. Throughout the last few billion years, they have played a major role in shaping the Earth as the planet we live in, and they continue to play a significant role in our everyday lives. Besides being an essential source of atmospheric oxygen, marine cyanobacteria are prolific secondary metabolite producers, often despite the exceptionally small genomes. Secondary metabolites produced by these organisms are diverse and complex; these include compounds, such as pigments and fluorescent dyes, as well as biologically-active compounds with a particular interest for the pharmaceutical industry. Cyanobacteria are currently regarded as an important source of nutrients and biofuels and form an integral part of novel innovative energy-efficient designs. Being autotrophic organisms, cyanobacteria are well suited for large-scale biotechnological applications due to the low requirements for organic nutrients. Recent advances in molecular biology techniques have considerably enhanced the potential for industries to optimize the production of cyanobacteria secondary metabolites with desired functions. This manuscript reviews the environmental role of marine cyanobacteria with a particular focus on their secondary metabolites and discusses current and future developments in both the production of desired cyanobacterial metabolites and their potential uses in future innovative projects.

  17. Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases.

    Science.gov (United States)

    Vann, Kendra R; Sedgeman, Carl A; Gopas, Jacob; Golan-Goldhirsh, Avi; Osheroff, Neil

    2015-07-28

    Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10-100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption.

  18. Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases

    Science.gov (United States)

    2016-01-01

    Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID:26132160

  19. Secondary metabolites: applications on cultural heritage.

    Science.gov (United States)

    Sasso, S; Scrano, L; Bonomo, M G; Salzano, G; Bufo, S A

    2013-01-01

    Biological sciences and related bio-technology play a very important role in research projects concerning protection and preservation of cultural heritage for future generations. In this work secondary metabolites of Burkholderia gladioli pv. agaricicola (Bga) ICMP 11096 strain and crude extract of glycoalkaloids from Solanaceae plants, were tested against a panel of microorganisms isolated from calcarenite stones of two historical bridges located in Potenza and in Campomaggiore (Southern Italy). The isolated bacteria belong to Bacillus cereus and Arthrobacter agilis species, while fungi belong to Aspergillus, Penicillium, Coprinellus, Fusarium, Rhizoctonio and Stemphylium genera. Bga broth (unfiltered) and glycoalkaloids extracts were able to inhibit the growth of all bacterial isolates. Bga culture was active against fungal colonies, while Solanaceae extract exerted bio-activity against Fusarium and Rhizoctonia genera.

  20. Formation of reactive metabolites from benzene

    International Nuclear Information System (INIS)

    Snyder, R.; Jowa, L.; Witz, G.; Kalf, G.; Rushmore, T.

    1986-01-01

    Rat liver mitoplasts were incubated first with [ 3 H]dGTP, to form DNA labeled in G, and then with [ 14 C]benzene. The DNA was isolated and upon isopycnic density gradient centrifugation in CsCl yielded a single fraction of DNA labeled with both [ 3 H] and [ 14 C]. These data are consistent with the covalent binding of one or more metabolites of benzene to DNA. The DNA was enzymatically hydrolyzed to deoxynucleosides and chromatographed to reveal at least seven deoxyguanosine adducts. Further studies with labeled deoxyadenine revealed one adduct on deoxyadenine. [ 3 H]Deoxyguanosine was reacted with [ 14 C]hydroquinone or benzoquinone. The product was characterized using uv, fluorescence, mass and NMR spectroscopy. A proposed structure is described. (orig.)

  1. Encapsulates for Food Bioconversions and Metabolite Production

    Science.gov (United States)

    Breguet, Véronique; Vojinovic, Vojislav; Marison, Ian W.

    The control of production costs in the food industry must be very strict as a result of the relatively low added value of food products. Since a wide variety of enzymes and/or cells are employed in the food industry for starch processing, cheese making, food preservation, lipid hydrolysis and other applications, immobilization of the cells and/or enzymes has been recognized as an attractive approach to improving food processes while minimizing costs. This is due to the fact that biocatalyst immobilization allows for easier separation/purification of the product and reutilization of the biocatalyst. The advantages of the use of immobilized systems are many, and they have a special relevance in the area of food technology, especially because industrial processes using immobilized biosystems are usually characterized by lower capital/energy costs and better logistics. The main applications of immobilization, related to the major processes of food bioconversions and metabolite production, will be described and discussed in this chapter.

  2. Atranorin - An Interesting Lichen Secondary Metabolite.

    Science.gov (United States)

    Studzinska-Sroka, Elzbieta; Galanty, Agnieszka; Bylka, Wieslawa

    2017-01-01

    Atranorin, a compound with the depside structure, is one of the most common lichen secondary metabolites, characteristic for numerous lichen families but rarely found in some mosses and higher plants. Over the years various biological properties of atranorin were examined. This review summarizes the studies on atranorin, focusing on a number of biological activities in different fields. The literature describes anti-inflammatory, analgesic, as well as wound healing, antibacterial, antifungal, cytotoxic, antioxidant, antiviral, and immunomodulatory activities of the depside. Furthermore, lack of toxicity of atranorin was confirmed in the animals' in vivo assays. In conclusion, atranorin seems to be an interesting lichen substance, which needs to be investigated in more detail in order to allow further applications, e.g. in pharmacy, medicine or cosmetology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Quantification of 3-nitrobenzanthrone-DNA adducts using online column-switching HPLC-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Gamboa da Costa, Gonçalo; Singh, Rajinder; Arlt, Volker M; Mirza, Amin; Richards, Meirion; Takamura-Enya, Takeji; Schmeiser, Heinz H; Farmer, Peter B; Phillips, David H

    2009-11-01

    The aromatic nitroketone 3-nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one; 3-NBA) is an extremely potent mutagen and a suspected human carcinogen detected in the exhaust of diesel engines and in airborne particulate matter. 3-NBA is metabolically activated via reduction of the nitro group to the hydroxylamine (N-OH-3-ABA) to form covalent DNA adducts. Thus far, the detection and quantification of covalent 3-NBA-DNA adducts has relied solely on (32)P-postlabeling methodologies. In order to expand the range of available techniques for the detection and improved quantification of 3-NBA-DNA adducts, we have developed a method based upon online column-switching HPLC coupled to electrospray tandem mass spectrometry, with isotopic dilution of (15)N-labeled internal standards. This methodology was applied to the determination of three 3-NBA-derived adducts: 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone (dG-N(2)-3-ABA), N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-N-3-ABA) and 2-(2'-deoxyguanosine-8-yl)-3-aminobenzanthrone (dG-C8-C2-3-ABA). Dose-dependent increases were observed for all three adducts when salmon testis DNA was reacted with N-acetoxy-3-aminobenzanthrone (N-AcO-3-ABA). dG-C8-C2-3-ABA was detected at much lower levels (overall 1%) than the other two adducts. DNA samples isolated from tissues of rats treated either intratracheally with 3-NBA or intraperitoneally with N-OH-3-ABA were analyzed by mass spectrometry, and the results compared to those obtained by (32)P-postlabeling. The method required 50 microg of hydrolyzed animal DNA on column and the limit of detection was 2.0 fmol for each adduct. dG-C8-C2-3-ABA was not observed in any of the samples providing confirmation that it is not formed in vivo. Linear regression analysis of the levels of dG-N(2)-3-ABA and dG-C8-N-3-ABA in the rat DNA showed a reasonable correlation between the two methods (R(2) = 0.88 and 0.93, respectively). In summary, the mass spectrometric method is a faster, more

  4. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  5. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin

    2013-04-25

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  6. Leach and mold resistance of essential oil metabolites

    Science.gov (United States)

    Carol A. Clausen; Vina W. Yang

    2011-01-01

    Purified primary metabolites from essential oils were previously shown to be bioactive inhibitors of mold fungi on unleached Southern pine sapwood, either alone or in synergy with a second metabolite. This study evaluated the leachability of these compounds in Southern pine that was either dip- or vacuum-treated. Following laboratory leach tests, specimens were...

  7. Towards systems metabolic engineering of streptomycetes for secondary metabolites production

    DEFF Research Database (Denmark)

    Robertsen, Helene Lunde; Weber, Tilmann; Kim, Hyun Uk

    2017-01-01

    Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical...... of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites....

  8. Pharmacokinetics of ifosfamide and some metabolites in children

    NARCIS (Netherlands)

    Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

    1998-01-01

    The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

  9. Aspergillus flavus secondary metabolites: more than just aflatoxins

    Science.gov (United States)

    Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

  10. Effect of metabolites produced by Trichoderma species against ...

    African Journals Online (AJOL)

    Metabolites released from Trichoderma viride, T. polysporum, T. hamatum and T. aureoviride were tested in culture medium against Ceratocystis paradoxa, which causes black seed rot in oil palm sprouted seeds. The Trichoderma metabolites had similar fungistatic effects on the growth of C. paradoxa except those from T.

  11. UV-guided isolation of fungal metabolites by HSCCC

    DEFF Research Database (Denmark)

    Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

    2005-01-01

    Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series...

  12. Automated de novo metabolite identification with mass spectrometry and cheminformatics

    NARCIS (Netherlands)

    Peironcely Miguel, Julio Eduardo

    2014-01-01

    In this thesis new algorithms and methods that enable the de novo identification of metabolites have been developed. The aim was to find methods to propose candidate structures for unknown metabolites using MSn data as starting point. These methods have been integrated into a semi-automated pipeline

  13. Fatty acid metabolites in rapidly proliferating breast cancer.

    Directory of Open Access Journals (Sweden)

    Joseph T O'Flaherty

    Full Text Available Breast cancers that over-express a lipoxygenase or cyclooxygenase are associated with poor survival possibly because they overproduce metabolites that alter the cancer's malignant behaviors. However, these metabolites and behaviors have not been identified. We here identify which metabolites among those that stimulate breast cancer cell proliferation in vitro are associated with rapidly proliferating breast cancer.We used selective ion monitoring-mass spectrometry to quantify in the cancer and normal breast tissue of 27 patients metabolites that stimulate (15-, 12-, 5-hydroxy-, and 5-oxo-eicosatetraenoate, 13-hydroxy-octadecaenoate [HODE] or inhibit (prostaglandin [PG]E2 and D2 breast cancer cell proliferation. We then related their levels to each cancer's proliferation rate as defined by its Mib1 score.13-HODE was the only metabolite strongly, significantly, and positively associated with Mib1 scores. It was similarly associated with aggressive grade and a key component of grade, mitosis, and also trended to be associated with lymph node metastasis. PGE2 and PGD2 trended to be negatively associated with these markers. No other metabolite in cancer and no metabolite in normal tissue had this profile of associations.Our data fit a model wherein the overproduction of 13-HODE by 15-lipoxygenase-1 shortens breast cancer survival by stimulating its cells to proliferate and possibly metastasize; no other oxygenase-metabolite pathway, including cyclooxygenase-PGE2/D2 pathways, uses this specific mechanism to shorten survival.

  14. Influence of abiotic stress signals on secondary metabolites in plants

    Science.gov (United States)

    Ramakrishna, Akula; Ravishankar, Gokare Aswathanarayana

    2011-01-01

    Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID:22041989

  15. Profiling and Identification of the Metabolites of Evodiamine in Rats ...

    African Journals Online (AJOL)

    linear ion trap Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap) method to profile and identify the metabolites of evodiamine in ... Keywords: Evodiamine, Ultra–performance liquid chromatography with linear ion trap-Orbitrap,. Hydroxyevodiamine ..... janthinellum and its application for metabolite identification in rat urine.

  16. Prototype of an intertwined secondary-metabolite supercluster

    Science.gov (United States)

    Phillipp Wiemann; Chun-Jun. Guo; Jonathan M. Palmer; Relebohile Sekonyela; Clay C.C. Wang; Nancy P. Keller

    2013-01-01

    The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the...

  17. Isolation and identification of two galangin metabolites from rat urine ...

    African Journals Online (AJOL)

    treatment of obesity and diabetes [3-4]. Natural products such as ... rat urine. In addition, the effects of these two metabolites on lipid ..... its five metabolites using ultra-fast liquid chromatography electrospray ionization tandem mass spectrometry to investigate influence of multiple-dose and food. J Chromatogr A 2014; 1358: ...

  18. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    Science.gov (United States)

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  19. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack

    NARCIS (Netherlands)

    Huber, M.; Epping, Janina; Schulze Gronover, C.; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Kollner, T.G.; Vogel, H.; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A.M.; Verhoeven, K.J.F.; Preite, V.; Gershenzon, J.; Erb, M.

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under

  20. Mycelial growth and antibacterial metabolite production by wild ...

    African Journals Online (AJOL)

    Russula sp. and Pycnoporus cinnabarinus (wild mushrooms) were subjected to laboratory cultivation by spore germination and tissue culturing on Sabouraud dextrose agar plates. Subsequently, the growth and production of metabolite(s) were monitored in submerged fermentation for 7days using agar diffusion method.

  1. The WEIZMASS spectral library for high-confidence metabolite identification

    NARCIS (Netherlands)

    Shahaf, Nir; Rogachev, Ilana; Heinig, Uwe; Meir, Sagit; Malitsky, Sergey; Battat, Maor; Wyner, Hilary; Zheng, Shuning; Wehrens, Ron; Aharoni, Asaph

    2016-01-01

    Annotation of metabolites is an essential, yet problematic, aspect of mass spectrometry (MS)-based metabolomics assays. The current repertoire of definitive annotations of metabolite spectra in public MS databases is limited and suffers from lack of chemical and taxonomic diversity. Furthermore,

  2. Biological treatment options for cyanobacteria metabolite removal--a review.

    Science.gov (United States)

    Ho, Lionel; Sawade, Emma; Newcombe, Gayle

    2012-04-01

    The treatment of cyanobacterial metabolites can consume many resources for water authorities which can be problematic especially with the recent shift away from chemical- and energy-intensive processes towards carbon and climate neutrality. In recent times, there has been a renaissance in biological treatment, in particular, biological filtration processes, for cyanobacteria metabolite removal. This in part, is due to the advances in molecular microbiology which has assisted in further understanding the biodegradation processes of specific cyanobacteria metabolites. However, there is currently no concise portfolio which captures all the pertinent information for the biological treatment of a range of cyanobacterial metabolites. This review encapsulates all the relevant information to date in one document and provides insights into how biological treatment options can be implemented in treatment plants for optimum cyanobacterial metabolite removal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Production of unusual dispiro metabolites in Pestalotiopsis virgatula endophyte cultures

    DEFF Research Database (Denmark)

    Kesting, Julie Regitze; Olsen, Lars; Stærk, Dan

    2011-01-01

    The endophytic fungus Pestalotiopsis virgatula, derived from the plant Terminalia chebula and previously found to produce a large excess of a single metabolite when grown in the minimal M1D medium, was induced to produce a variety of unusual metabolites by growing in potato dextrose broth medium....... Analysis of the fermentation medium extract was performed using an HPLC-PDA-MS-SPE-NMR hyphenated system, which led to the identification of a total of eight metabolites (1-8), six of which are new. Most of the metabolites are structurally related and are derivatives of benzo[c]oxepin, rare among natural...... supported by time-dependent density-functional theory calculations (B3LYP/TZVP level). This work demonstrates that a largely complete structure elucidation of numerous metabolites present in a raw fermentation medium extract can be performed by the HPLC-SPE-NMR technique using only a small amount...

  4. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  5. The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

    Science.gov (United States)

    Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

    2018-05-01

    DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Plasma Metabolite Profiles in Response to Chronic Exercise.

    Science.gov (United States)

    Brennan, Andrea M; Benson, Mark; Morningstar, Jordan; Herzig, Matthew; Robbins, Jeremy; Gerszten, Robert E; Ross, Robert

    2018-03-05

    High throughput profiling of metabolic status (metabolomics) allows for the assessment of small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe the changes in a diverse set of plasma metabolite profiles in patients undergoing chronic exercise training and assess the relationship between metabolites and cardiometabolic response to exercise. A secondary analysis was performed in 216 middle-aged abdominally obese men and women ([mean (SD)], 52.4 (8.0) years) randomized into one of four groups varying in exercise amount and intensity for 6 months duration: high amount high intensity, high amount low intensity, low amount low intensity, and control. 147 metabolites were profiled by liquid chromatography-tandem mass spectrometry. No significant differences in metabolite changes between specific exercise groups were observed; therefore, subsequent analyses were collapsed across exercise groups. There were no significant differences in metabolite changes between the exercise and control groups after 24 weeks at a Bonferroni-adjusted statistical significance (p < 3.0 x 10). Seven metabolites changed in the exercise group compared to the control group at p < 0.05. Changes in several metabolites from distinct metabolic pathways were associated with change in cardiometabolic risk traits, and three baseline metabolite levels predicted changes in cardiometabolic risk traits. Metabolomic profiling revealed no significant plasma metabolite changes between exercise compared to control after 24-weeks at Bonferroni significance. However, we identified circulating biomarkers that were predictive or reflective of improvements in cardiometabolic traits in the exercise group.

  7. Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone

    International Nuclear Information System (INIS)

    Deslypere, J.P.; Sayed, A.; Vermeulen, A.; Wiers, P.W.

    1981-01-01

    The influence of age on the metabolic pattern of [4- 14 C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4- 14 C]testosterone metabolites: together with their suephoconjugates as well as with 5α- and 5β-androstane-3α, 17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4- 14 C]testosterone was significantly (P 14 C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both [4- 14 C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation. (author)

  8. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

    DEFF Research Database (Denmark)

    Jančič, Sašo; Frisvad, Jens Christian; Kocev, Dragi

    2016-01-01

    of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known...... to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although...... the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has...

  9. Brain metabolites of lindane and related isomers: identification by negative ion mass spectrometry.

    Science.gov (United States)

    Artigas, F; Martínez, E; Camón, L; Gelpí, E; Rodríguez-Farré, E

    1988-04-01

    The application of a new method of gas chromatography-mass spectrometry (GC-MS) to the study of some aspects of the metabolism of hexachlorocyclohexanes is presented. Instead of the classical mode of ionization (Electron Impact, EI), this method uses chemical ionization, recording only the negative ions produced. This enables a tremendous enhancement of the signal when chlorinated compounds elute from the chromatographic column. The mass spectra obtained consist generally in the ions corresponding to the molecular weight of the compound analyzed. The sensitivity of the method is higher than any other GC method described: the limit of detection of several organochlorine compounds can be as low as 60 femtograms. Using this method we have been able to identify several Lindane metabolites (tetra-, penta- and hexachlorocyclohexenes, tetra- and pentachlorobenzene) in rat brain homogenates without any purification step. Using this method, a quantitative study of the main metabolites found in brain after treatment with 4 different HCH isomers has been performed. This study reveals that the HCH isomers are cleared from the brain via different metabolic pathways, with a rate of production of metabolites which is inversely correlated to their half lives in brain.

  10. Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting

    Science.gov (United States)

    Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó.; Kuttner, Eva; Ásgeirsdóttir, Margrét E.; Young, Louise C.; Green, David H.; Edrada-Ebel, Ruangelie; Duncan, Katherine R.

    2016-01-01

    The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149–2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations. PMID:26761036

  11. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

    2016-09-30

    Fusarium head blight (FHB), primarily caused by Fusarium graminearum , is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum , such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  12. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Miroslava Cuperlovic-Culf

    2016-09-01

    Full Text Available Fusarium head blight (FHB, primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  13. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  14. Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

    Science.gov (United States)

    Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

    2016-01-01

    Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID

  15. Direct detection of glucuronide metabolites of lidocaine in sheep urine.

    Science.gov (United States)

    Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

    2018-02-15

    The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  16. An Invasive Plant Promotes Its Arbuscular Mycorrhizal Symbioses and Competitiveness through Its Secondary Metabolites: Indirect Evidence from Activated Carbon

    Science.gov (United States)

    Yuan, Yongge; Tang, Jianjun; Leng, Dong; Hu, Shuijin; Yong, Jean W. H.; Chen, Xin

    2014-01-01

    Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC), a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM) symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1–3) with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC) of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts. PMID:24817325

  17. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Directory of Open Access Journals (Sweden)

    Yongge Yuan

    Full Text Available Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC, a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3 with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  18. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Science.gov (United States)

    Yuan, Yongge; Tang, Jianjun; Leng, Dong; Hu, Shuijin; Yong, Jean W H; Chen, Xin

    2014-01-01

    Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC), a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM) symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3) with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC) of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  19. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites

    International Nuclear Information System (INIS)

    Louisse, Jochem; Bai Yanqing; Verwei, Miriam; Sandt, Johannes J.M. van de; Blaauboer, Bas J.; Rietjens, Ivonne M.C.M.

    2010-01-01

    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA) metabolite of ethylene glycol monomethyl ether as the model compound. The results obtained demonstrate an MAA-induced decrease of the intracellular pH (pH i ) of embryonic BALB/c-3T3 cells as well as of embryonic stem (ES)-D3 cells, at concentrations that affect ES-D3 cell differentiation. These results suggest a mechanism for MAA-mediated embryotoxicity similar to the mechanism of embryotoxicity of the drugs valproic acid and acetazolamide (ACZ), known to decrease the pH i in vivo, and therefore used as positive controls. The embryotoxic alkoxyacetic acid metabolites ethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid also caused an intracellular acidification of BALB/c-3T3 cells at concentrations that are known to inhibit ES-D3 cell differentiation. Two other embryotoxic compounds, all-trans-retinoic acid and 5-fluorouracil, did not decrease the pH i of embryonic cells at concentrations that affect ES-D3 cell differentiation, pointing at a different mechanism of embryotoxicity of these compounds. MAA and ACZ induced a concentration-dependent inhibition of ES-D3 cell differentiation, which was enhanced by amiloride, an inhibitor of the Na + /H + -antiporter, corroborating an important role of the pH i in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH i may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

  20. Winery vermicomposts to control the leaching of diuron, imidacloprid and their metabolites: role of dissolved organic carbon content.

    Science.gov (United States)

    Fernández-Bayo, Jesús D; Nogales, Rogelio; Romero, Esperanza

    2015-01-01

    Soil organic amendment addition is an effective practice in Mediterranean areas due to its associated high agricultural benefits and its potential to reduce the pesticide impact on water resources. However, their metabolites have received scarce attention, even when they may pose more risk than their parent compounds. Two winery vermicomposts obtained from spent grape marc (V1) and the mixture vine shoot-biosolid vinasses (V2) have been investigated as low cost organic amendments to minimize the leaching of diuron, imidacloprid and their metabolites in columns packed with a sandy loam (S1) and a silty-clay loam soil (S2) under steady state flow conditions. In the unamended soil columns, leached amounts of diuron were 75% and 53% in S1 and S2, respectively. Its metabolites (3-(3,4-dichlorophenyl)-1-methylurea, DPMU; and 3,4-dichlorophenylurea, DPU) percolated less than 35% of the total applied amount. The amount of the metabolite 3,4-dichloroaniline (DCA) was 2% and 30% for S1 and S2, respectively. Leaching of imidacloprid was 79% and 96% for S1 and S2, respectively, while its metabolite 6-chloronicotinic acid (CNA) was entirely leached. In the vermicompost-amended columns, the leaching of diuron was reduced 2 to 3-fold. DPMU and DPU were also significantly reduced (more than 6-fold). DCA did not appear in any of the leachates of the amended soil columns. Imidacloprid leaching was reduced 1 to 2-folds in the amended columns. The amendments did not affect the transport of CNA. The dissolved organic carbon (DOC) from the vermicomposts did not enhance pesticide transport throughout the soil in any case. This qualitative study presents these vermicomposts as an effective potential low-cost tool in reducing pesticide and metabolite leaching. The next step would be to test them under more realistic conditions.

  1. Arachidonic acid metabolites in pathogenic yeasts

    Directory of Open Access Journals (Sweden)

    Ells Ruan

    2012-08-01

    Full Text Available Abstract Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2α and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

  2. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  3. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    Directory of Open Access Journals (Sweden)

    Valentin Bhimba B

    2011-12-01

    Full Text Available Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites were characterized by gas chromatography-mass spectrometry (GC-MS analysis. Conclusions: Based on the present study, it can be inferred that the bioassay guided fractionation and purification of D. nigra may come up with potent bioactive drug.

  4. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...

  5. Natural occurrence of fungi and fungal metabolites in moldy tomatoes

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    Fresh tomatoes, homegrown and from supermarkets, with developing fungal lesions were collected. Each lesion was sampled, and the resulting fungal cultures were identified morphologically, and extracted for analyzes of secondary metabolites. The tomatoes were incubated at 25 degreesC for a week....... extracted, and analyzed for fungal metabolites. Extracts from pure cultures were compared with extracts from the moldy tomatoes and fungal metabolite standards in two HPLC systems with DAD and FLD detection. The results showed that Penicillium tularense, Stemphylium eturmiunum. and S. cf. lycopersici were...

  6. Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites.

    OpenAIRE

    Weiss, S J; Regiani, S

    1984-01-01

    Triggered neutrophils rapidly degraded labeled matrices secreted by cultured, venous endothelial cells via a process dependent on elastase but not oxygen metabolites. In the presence of high concentrations of alpha-1-proteinase inhibitor, the ability of the stimulated neutrophil to solubilize the matrix was impaired. However, at lower concentrations of alpha-1-proteinase inhibitor the neutrophil could enhance the degradative potential of its released elastase by a H2O2-dependent process. Coin...

  7. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Science.gov (United States)

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  8. Drug and chemical metabolites in clinical toxicology investigations: the importance of ethylene glycol, methanol and cannabinoid metabolite analyses.

    Science.gov (United States)

    Fraser, Albert D; Coffin, Lawrence; Worth, David

    2002-10-01

    Metabolic pathways in humans have been elucidated for most therapeutic drugs, drugs of abuse, and various chemical/solvents. In most drug overdose cases and chemical exposures, laboratory analysis is directed toward identification and quantitation of the unchanged drug or chemical in a biologic fluid such as serum or whole blood. Specifically, most clinical laboratories routinely screen and quantitate unchanged methanol and/or ethylene glycol in suspected poisonings without toxic metabolite analysis. Martin-Amat established in 1978 that methanol associated toxicity to the optic nerve in human poisonings was due to the toxic metabolite formic acid found in methanol poisonings and not due to the direct action by unchanged methanol. Jacobsen reported in 1981 that ethylene glycol central nervous system and renal toxicity were primarily due to one acidic metabolite (glycolic acid) and not due to unchanged ethylene glycol. The first objective of this review is to describe clinical experience with formic acid and glycolic acid analysis in methanol and ethylene glycol human poisonings. Drug metabolite analysis also provides useful information in the assessment and monitoring of drug use in psychiatry and substance abusing populations. Drug analysis in substance abuse monitoring is focused on urine analysis of one or more major metabolites, and less frequently on the unchanged drug(s). Serial monitoring of the major urinary cannabinoid metabolite (delta(9)-THC-COOH) to creatinine ratios in paired urine specimens (collected at least 24 h apart) could differentiate new marijuana or hashish use from residual cannabinoid metabolite excretion in urine after drug use according to Huestis. The second objective is to demonstrate that creatinine corrected urine specimens positive for cannabinoids may help differentiate new marijuana use from the excretion of residual delta(9) -THC-COOH in chronic users of marijuana or hashish. Analysis of toxic chemical metabolites are helpful in

  9. Characterization of forsythoside A metabolites in rats by a combination of UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques.

    Science.gov (United States)

    Wang, Fei; Cao, Guang-Shang; Li, Yun; Xu, Lu-Lu; Wang, Zhi-Bin; Liu, Ying; Lu, Jian-Qiu; Zhang, Jia-Yu

    2018-05-01

    Forsythoside A (FTA), the main active constituent isolated from Fructus Forsythiae, has various biological functions including anti-oxidant, anti-viral and anti-microbial activities. However, while research on FTA has been mainly focused on the treatment of diseases on a material basis, FTA metabolites in vivo have not been comprehensively evaluated. Here, a rapid and sensitive method using a UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques including high-resolution extracted ion chromatograms, multiple mass defect filters and diagnostic product ions was developed for the screening and identification of FTA metabolites in rats. As the result, a total of 43 metabolites were identified in biological samples including 42 metabolites in urine, 22 metabolites in plasma and 15 metabolites in feces. These results demonstrated that FTA underwent a series of in vivo metabolic reactions including methylation, dimethylation, sulfation, glucuronidation, diglucuronidation, cysteine conjugation and their composite reactions. The research enhanced our understanding of FTA metabolism and built a foundation for further toxicity and safety studies. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Detection of mastitis pathogens by analysis of volatile bacterial metabolites

    NARCIS (Netherlands)

    Hettinga, K.A.; Valenberg, van H.J.F.; Lam, T.J.G.M.; Hooijdonk, van A.C.M.

    2008-01-01

    The ability to detect mastitis pathogens based on their volatile metabolites was studied. Milk samples from cows with clinical mastitis, caused by Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus uberis, Streptococcus dysgalactiae, and Escherichia coli were collected. In

  11. Analytical Methods for the Quantification of Histamine and Histamine Metabolites.

    Science.gov (United States)

    Bähre, Heike; Kaever, Volkhard

    2017-01-01

    The endogenous metabolite histamine (HA) is synthesized in various mammalian cells but can also be ingested from exogenous sources. It is involved in a plethora of physiological and pathophysiological processes. So far, four different HA receptors (H 1 R-H 4 R) have been described and numerous HAR antagonists have been developed. Contemporary investigations regarding the various roles of HA and its main metabolites have been hampered by the lack of highly specific and sensitive analytic methods for all of these analytes. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is the method of choice for identification and sensitive quantification of many low-molecular weight endogenous metabolites. In this chapter, different methodological aspects of HA quantification as well as recommendations for LC-MS/MS methods suitable for analysis of HA and its main metabolites are summarized.

  12. Characterization and identification of in vitro metabolites of ...

    African Journals Online (AJOL)

    Characterization and identification of in vitro metabolites of (-)-epicatechin using ultra-high performance liquid chromatography-mass spectrometry. Rui Jun Cai, Xiao Ling Yin, Jing Liu, Da Xu Qin, Gui Zhen Zhao ...

  13. β-Orcinol Metabolites from the Lichen Hypotrachyna revoluta

    Directory of Open Access Journals (Sweden)

    Panagiota Papadopoulou

    2007-05-01

    Full Text Available Four new β-orcinol metabolites, hypotrachynic acid (1, deoxystictic acid (2, cryptostictinolide (3 and 8 ́-methylconstictic acid (4 along with the metabolites 8 ́-methylstictic acid (5, 8 ́-methylmenegazziaic acid (6, stictic acid (7, 8 ́-ethylstictic acid (8 and atranorin (9, that have been previously described, were isolated for the first time from the tissue extracts of the lichen Hypotrachyna revoluta (Flörke Hale. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analyses. Radical scavenging activity (RSA of the metabolites isolated in adequate amounts, was evaluated using luminol chemiluminescence and comparison with Trolox®.

  14. Metabolites: messengers between the microbiota and the immune system.

    Science.gov (United States)

    Levy, Maayan; Thaiss, Christoph A; Elinav, Eran

    2016-07-15

    The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases. © 2016 Levy et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Isolation and identification of two galangin metabolites from rat urine ...

    African Journals Online (AJOL)

    Isolation and identification of two galangin metabolites from rat urine and determination of their in vitro hypolipidemic activity. Xuguang Zhang, Shouqian Cheng, Hailong Li, Xiaopo Zhang, Feng Chen, Youbin Li, Junqing Zhang, Yinfeng Tan ...

  16. Identification, synthesis and pharmacological activity of moxonidine metabolites.

    Science.gov (United States)

    Wirth, David D; He, Minxia M; Czeskis, Boris A; Zimmerman, Karen M; Roettig, Ulrike; Stenzel, Wolfgang; Steinberg, Mitchell I

    2002-01-01

    The metabolism of moxonidine, 4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methyl-5-pyrimidinamine, LY326869, in rats, mice, dogs, and humans has been examined. At least 17 metabolites were identified or tentatively identified in the different species by HPLC, LC/MS and LC/MS/MS. The identities of seven of the major metabolites have been verified by independent synthesis. The metabolites are generally derived from oxidation and conjugation pathways. Oxidation occurred at the imidazolidine ring as well as the methyl at the 2 position of the pyrimidine ring. All seven metabolites were examined in the spontaneously hypertensive rats (3 mg kg(-1), i.v.) for pressure and heart rate. Only one, 2-hydroxymethyl-4-chloro-5-(imidazolidin-2-ylidenimino)-6-methoxypyrimidine, exerted a short-lasting decrease in blood pressure, albeit attenuated in magnitude compared to moxonidine.

  17. IN VITRO CYTOTOXICITY OF BTEX METABOLITES IN HELA CELL LINES

    Science.gov (United States)

    Fuel leakage from underground storage tanks is a major source of groundwater contamination. Although the toxicity of regulated compounds such as benzene, toluene, ethylbenzene, and xylene (BTEX) are well recognized, the cytotoxicity of their metabolites has not been studied exte...

  18. Metabolites Produced by Nitrogen-Fixing Nostoc Species

    Czech Academy of Sciences Publication Activity Database

    Dembitsky, V. M.; Řezanka, Tomáš

    2005-01-01

    Roč. 50, č. 5 (2005), s. 363-391 ISSN 0015-5632 Institutional research plan: CEZ:AV0Z5020903 Keywords : nostoc * metabolites * cyanobacteria Subject RIV: EE - Microbiology, Virology Impact factor: 0.918, year: 2005

  19. Bioactive Metabolites from Spilanthes acmella Murr.

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2009-02-01

    Full Text Available Spilanthes acmella Murr. (Compositae has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains of microorganisms were performed. Results showed that fractions from the chloroform and methanol extracts inhibited the growth of many tested organisms, e.g. Corynebacterium diphtheriae NCTC 10356 with minimum inhibitory concentration (MIC of 64-256 mg/mL and Bacillus subtilis ATCC 6633 with MIC of 128-256 mg/mL. The tested fractions all exhibited antioxidant properties in both DPPH and SOD assays. Potent radical scavenging activity was observed in the DPPH assay. No cytotoxic effects of the extracts against KB and HuCCA-1 cell lines were evident. Bioassay-guided isolation resulted in a diverse group of bioactive compounds such as phenolics [vanillic acid (2, trans-ferulic acid (5 and trans-isoferulic acid (6], coumarin (scopoletin, 4 and triterpenoids like 3-acetylaleuritolic acid (1, b-sitostenone (3, stigmasterol and stigmasteryl-3-O-b-D-glucopyranosides, in addition to a mixture of stigmasteryl-and b-sitosteryl-3-O-b-D-glucopyranosides. The compounds 1–6 represent bioactive metabolites of S. acmella Murr. that were never previously reported. Our findings demonstrate for the first time the potential benefits of this medicinal plant as a rich source of high therapeutic value compounds for medicines, cosmetics, supplements and as a health food.

  20. Volatile metabolites of pathogens: a systematic review.

    Directory of Open Access Journals (Sweden)

    Lieuwe D J Bos

    2013-05-01

    Full Text Available Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs, which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically

  1. Zinc protoporphyrin: A metabolite with a mission.

    Science.gov (United States)

    Labbé, R F; Vreman, H J; Stevenson, D K

    1999-12-01

    Zinc protoporphyrin (ZnPP) is a normal metabolite that is formed in trace amounts during heme biosynthesis. The final reaction in the biosynthetic pathway of heme is the chelation of iron with protoporphyrin. During periods of iron insufficiency or impaired iron utilization, zinc becomes an alternative metal substrate for ferrochelatase, leading to increased ZnPP formation. Evidence suggests that this metal substitution is one of the first biochemical responses to iron depletion, causing increased ZnPP to appear in circulating erythrocytes. Because this zinc-for-iron substitution occurs predominantly within the bone marrow, the ZnPP/heme ratio in erythrocytes reflects iron status in the bone marrow. In addition, ZnPP may regulate heme catabolism through competitive inhibition of heme oxygenase, the rate-limiting enzyme in the heme degradation pathway that produces bilirubin and carbon monoxide. Physiological roles, especially relating to carbon monoxide and possibly nitric oxide production, have been suggested for ZnPP. Clinically, ZnPP quantification is valuable as a sensitive and specific tool for evaluating iron nutrition and metabolism. Diagnostic determinations are applicable in a variety of clinical settings, including pediatrics, obstetrics, and blood banking. ZnPP analytical methodologies for clinical studies are discussed. In addition to diagnostic tests and metabolic studies, ZnPP has a potential therapeutic application in controlling bilirubin formation in neonates as a preventive measure for hyperbilirubinemia. Biochemical research techniques, both in vivo and in vitro, are described for further studies into the role of ZnPP in metabolism and physiology.

  2. Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhan, Max; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-08-19

    Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme is recognized as the most promising approach to cocaine overdose treatment. The actual enzyme, known as RBP-8000, under current clinical development for cocaine overdose treatment is our previously designed T172R/G173Q mutant of bacterial cocaine esterase (CocE). The T172R/G173Q mutant is effective in hydrolyzing cocaine but inactive against benzoylecgonine (a major, biologically active metabolite of cocaine). Unlike cocaine itself, benzoylecgonine has an unusually stable zwitterion structure resistant to further hydrolysis in the body and environment. In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. Because CocE and its mutants are all active against cocaine and inactive against benzoylecgonine, one might simply assume that other enzymes that are active against cocaine are also inactive against benzoylecgonine. Here, through combined computational modeling and experimental studies, we demonstrate for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoylecgonine in vitro and in vivo. This sets the stage for advanced studies to design more efficient mutant enzymes valuable for the development of an ideal cocaine overdose enzyme therapy and for benzoylecgonine detoxification in the environment.

  3. Separation of prostaglandin metabolites on sephadex LH 20 columns

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Bukhave, K.

    1978-01-01

    Sephadex LH 20 columns have been investigated for the separation of initial prostaglandin metabolites. Solvent systems are described for the separation of the free acids of 15-keto-dihydro-PGE, 15-keto-PGE, PGE, and PGF(1a). Further, one of the solvent systems is described for the separation...... of pulmonary metabolites of PGE and PGF(1a), and another one for separation of dihydro-PGE and PGE....

  4. Metabolite profiles and the risk of developing diabetes

    OpenAIRE

    T J Wang; M G Larson; R S Vasan; S Cheng; E P Rhee; E McCabe; G D Lewis; C S Fox; P F Jacques; C Fernandez; C J ODonnell; S A Carr; V K Mootha; J C Florez; A Souza

    2011-01-01

    Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles could predict the development of diabetes. Among 2,422 normoglycemic individuals followed for 12 years, 201 developed diabetes. Amino acids, amines, and other polar metabolites were profiled in baseline specimens using liquid chromatography-tandem mass spectrometry. Cases and controls were matched for age, body mass index and fasting g...

  5. Investigation of metabolites for estimating blood deposition time.

    Science.gov (United States)

    Lech, Karolina; Liu, Fan; Davies, Sarah K; Ackermann, Katrin; Ang, Joo Ern; Middleton, Benita; Revell, Victoria L; Raynaud, Florence J; Hoveijn, Igor; Hut, Roelof A; Skene, Debra J; Kayser, Manfred

    2018-01-01

    Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor's alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.

  6. Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

    Science.gov (United States)

    Goggin, Melissa M; Nguyen, An; Janis, Gregory C

    2017-06-01

    The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Metabolites of Siamenoside I and Their Distributions in Rats

    Directory of Open Access Journals (Sweden)

    Xue-Rong Yang

    2016-01-01

    Full Text Available Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

  8. Lichen secondary metabolites affect growth of Physcomitrella patens by allelopathy.

    Science.gov (United States)

    Goga, Michal; Antreich, Sebastian J; Bačkor, Martin; Weckwerth, Wolfram; Lang, Ingeborg

    2017-05-01

    Lichen secondary metabolites can function as allelochemicals and affect the development and growth of neighboring bryophytes, fungi, vascular plants, microorganisms, and even other lichens. Lichen overgrowth on bryophytes is frequently observed in nature even though mosses grow faster than lichens, but there is still little information on the interactions between lichens and bryophytes.In the present study, we used extracts from six lichen thalli containing secondary metabolites like usnic acid, protocetraric acid, atranorin, lecanoric acid, nortistic acid, and thamnolic acid. To observe the influence of these metabolites on bryophytes, the moss Physcomitrella patens was cultivated for 5 weeks under laboratory conditions and treated with lichen extracts. Toxicity of natural mixtures of secondary metabolites was tested at three selected doses (0.001, 0.01, and 0.1 %). When the mixture contained substantial amounts of usnic acid, we observed growth inhibition of protonemata and reduced development of gametophores. Significant differences in cell lengths and widths were also noticed. Furthermore, usnic acid had a strong effect on cell division in protonemata suggesting a strong impact on the early stages of bryophyte development by allelochemicals contained in the lichen secondary metabolites.Biological activities of lichen secondary metabolites were confirmed in several studies such as antiviral, antibacterial, antitumor, antiherbivore, antioxidant, antipyretic, and analgetic action or photoprotection. This work aimed to expand the knowledge on allelopathic effects on bryophyte growth.

  9. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-10-01

    Full Text Available Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

  10. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential.

    Science.gov (United States)

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-10-20

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

  11. Analysis of Particulate and Dissolved Metabolite Pools at Station ALOHA

    Science.gov (United States)

    Boysen, A.; Carlson, L.; Hmelo, L.; Ingalls, A. E.

    2016-02-01

    Metabolomic studies focus on identifying and quantifying the small organic molecules that are the currency by which an organism lives and dies. Metabolite profiles of microorganisms have the potential to elucidate mechanisms of chemically mediated interactions that influence the success of microbial groups living in a complex environment. However, the chemical diversity of metabolites makes resolving a wide range of compounds analytically challenging. As such, metabolomics has lagged behind other genomic analyses. Here we conduct targeted analysis of over 200 primary and secondary metabolites present in the intracellular and extracellular metabolite pools at Station ALOHA using both reverse phase and hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. We selected the metabolites in our method due to their known importance in primary metabolism, secondary metabolism, and interactions between marine microorganisms such as nutrient exchange, growth promotion, and cell signaling. Through these analyses we obtain a snapshot of microbial community status that, blended with other forms of genomic data, can further our understanding of microbial dynamics. We hypothesize that monitoring a large suite of important metabolites across environmental gradients and diurnal cycles can elucidate factors controlling the distribution and activity of important microbial groups.

  12. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

    Science.gov (United States)

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-01-01

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology. PMID:27775594

  13. Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus.

    Science.gov (United States)

    Bracarense, Adriana A P; Takahashi, Jacqueline A

    2014-01-01

    Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration) in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 2(2) full factorial planning (ANOVA) and on a 2(3) factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC.

  14. Structural Characterization of Anticancer Drug Paclitaxel and Its Metabolites Using Ion Mobility Mass Spectrometry and Tandem Mass Spectrometry

    Science.gov (United States)

    Lee, Hong Hee; Hong, Areum; Cho, Yunju; Kim, Sunghwan; Kim, Won Jong; Kim, Hugh I.

    2016-02-01

    Paclitaxel (PTX) is a popular anticancer drug used in the treatment of various types of cancers. PTX is metabolized in the human liver by cytochrome P450 to two structural isomers, 3'- p-hydroxypaclitaxel (3 p-OHP) and 6α-hydroxypaclitaxel (6α-OHP). Analyzing PTX and its two metabolites, 3 p-OHP and 6α-OHP, is crucial for understanding general pharmacokinetics, drug activity, and drug resistance. In this study, electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) and collision induced dissociation (CID) are utilized for the identification and characterization of PTX and its metabolites. Ion mobility distributions of 3 p-OHP and 6α-OHP indicate that hydroxylation of PTX at different sites yields distinct gas phase structures. Addition of monovalent alkali metal and silver metal cations enhances the distinct dissociation patterns of these structural isomers. The differences observed in the CID patterns of metalated PTX and its two metabolites are investigated further by evaluating their gas-phase structures. Density functional theory calculations suggest that the observed structural changes and dissociation pathways are the result of the interactions between the metal cation and the hydroxyl substituents in PTX metabolites.

  15. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite...

  16. Phytochemical background matters for bioactivity of plant metabolites : a case study with pyrrolizidine alkaloids

    NARCIS (Netherlands)

    Liu, X.

    2016-01-01

    The plant kingdom has evolved an enormous number of chemically diverse metabolites that protect plants from biotic and abiotic stresses. The large number of metabolites in a given plant indicates interactions between metabolites are very likely. The co-occurrence of plant metabolites comprise a

  17. The effects of cadmium chloride on secondary metabolite production in Vitis vinifera cv. cell suspension cultures.

    Science.gov (United States)

    Cetin, Emine Sema; Babalik, Zehra; Hallac-Turk, Filiz; Gokturk-Baydar, Nilgun

    2014-09-23

    Plant secondary metabolites are possess several biological activities such as anti-mutagenic, anti-carcinogenic, anti-aging, etc. Cell suspension culture is one of the most effective systems to produce secondary metabolites. It is possible to increase the phenolic compounds and tocopherols by using cell suspensions. Studies on tocopherols production by cell suspension cultures are seldom and generally focused on seed oil plants. Although fresh grape, grape seed, pomace and grape seed oil had tocopherols, with our best knowledge, there is no research on tocopherol accumulation in the grape cell suspension cultures. In this study, it was aimed to determine the effects of cadmium chloride treatments on secondary metabolite production in cell suspension cultures of grapevine. Cell suspensions initiated from callus belonging to petiole tissue was used as a plant material. Cadmium chloride was applied to cell suspension cultures in different concentration (1.0 mM and 1.5 mM) to enhance secondary metabolite (total phenolics, total flavanols, total flavonols, trans-resveratrol, and α-, β-, γ- δ-tocopherols) production. Cells were harvested at two days intervals until the 6th day of cultures. Amounts of total phenolics, total flavanols and total flavonols; trans-resveratrol and tocopherols (α-, β-, γ- and δ-tocopherols) and dry cell weights were determined in the harvested cells. Phenolic contents were significantly affected by the sampling time and cadmium concentrations. The highest values of total phenolic (168.82 mg/100 g), total flavanol (15.94 mg/100 g), total flavonol (14.73 mg/100 g) and trans-resveratrol (490.76 μg/100 g) were found in cells treated with 1.0 mM CdCl2 and harvested at day 2. Contents of tocopherols in the cells cultured in the presence of 1.0 mM CdCl2 gradually increased during the culture period and the highest values of α, β and γ tocopherols (145.61, 25.52 and 18.56 μg/100 g) were detected in the cell cultures collected at day 6

  18. The effects of cadmium chloride on secondary metabolite production in Vitis vinifera cv. cell suspension cultures

    Directory of Open Access Journals (Sweden)

    Emine Sema Cetin

    2014-01-01

    Full Text Available BACKGROUND: Plant secondary metabolites are possess several biological activities such as anti-mutagenic, anti-carcinogenic, anti-aging, etc. Cell suspension culture is one of the most effective systems to produce secondary metabolites. It is possible to increase the phenolic compounds and tocopherols by using cell suspensions. Studies on tocopherols production by cell suspension cultures are seldom and generally focused on seed oil plants. Although fresh grape, grape seed, pomace and grape seed oil had tocopherols, with our best knowledge, there is no research on tocopherol accumulation in the grape cell suspension cultures. In this study, it was aimed to determine the effects of cadmium chloride treatments on secondary metabolite production in cell suspension cultures of grapevine. Cell suspensions initiated from callus belonging to petiole tissue was used as a plant material. Cadmium chloride was applied to cell suspension cultures in different concentration (1.0 mM and 1.5 mM to enhance secondary metabolite (total phenolics, total flavanols, total flavonols, trans-resveratrol, and α-, β-, γ- δ-tocopherols production. Cells were harvested at two days intervals until the 6th day of cultures. Amounts of total phenolics, total flavanols and total flavonols; trans-resveratrol and tocopherols (α-, β-, γ- and δ-tocopherols and dry cell weights were determined in the harvested cells. RESULTS: Phenolic contents were significantly affected by the sampling time and cadmium concentrations. The highest values of total phenolic (168.82 mg/100 g, total flavanol (15.94 mg/100 g, total flavonol (14.73 mg/100 g and trans-resveratrol (490.76 µg/100 g were found in cells treated with 1.0 mM CdCl2 and harvested at day 2. Contents of tocopherols in the cells cultured in the presence of 1.0 mM CdCl2 gradually increased during the culture period and the highest values of α, β and γ tocopherols (145.61, 25.52 and 18.56 µg/100 g were detected in the cell

  19. Severe drought stress is affecting selected primary metabolites, polyphenols, and volatile metabolites in grapevine leaves (Vitis vinifera cv. Pinot noir).

    Science.gov (United States)

    Griesser, Michaela; Weingart, Georg; Schoedl-Hummel, Katharina; Neumann, Nora; Becker, Manuel; Varmuza, Kurt; Liebner, Falk; Schuhmacher, Rainer; Forneck, Astrid

    2015-03-01

    Extreme weather conditions with prolonged dry periods and high temperatures as well as heavy rain events can severely influence grapevine physiology and grape quality. The present study evaluates the effects of severe drought stress on selected primary metabolites, polyphenols and volatile metabolites in grapevine leaves. Among the 11 primary metabolites, 13 polyphenols and 95 volatiles which were analyzed, a significant discrimination between control and stressed plants of 7 primary metabolites, 11 polyphenols and 46 volatile metabolites was observed. As single parameters are usually not specific enough for the discrimination of control and stressed plants, an unsupervised (PCA) and a supervised (PLS-DA) multivariate approach were applied to combine results from different metabolic groups. In a first step a selection of five metabolites, namely citric acid, glyceric acid, ribose, phenylacetaldehyde and 2-methylbutanal were used to establish a calibration model using PLS regression to predict the leaf water potential. The model was strong enough to assign a high number of plants correctly with a correlation of 0.83. The PLS-DA provides an interesting approach to combine data sets and to provide tools for the specific evaluation of physiological plant stresses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. In situ uranium stabilization by microbial metabolites

    International Nuclear Information System (INIS)

    Turick, Charles E.; Knox, Anna S.; Leverette, Chad L.; Kritzas, Yianne G.

    2008-01-01

    Microbial melanin production by autochthonous bacteria was explored in this study as a means to increase U immobilization in U contaminated soil. This article demonstrates the application of bacterial physiology and soil ecology for enhanced U immobilization in order to develop an in situ, U bio-immobilization technology. We have demonstrated microbial production of a metal chelating biopolymer, pyomelanin, in U contaminated soil from the Tims Branch area of the Department of Energy (DOE), Savannah River Site (SRS), South Carolina, as a result of tyrosine amendments. Bacterial densities of pyomelanin producers were >10 6 cells per g wet soil. Pyomelanin demonstrated U complexing and mineral binding capacities at pH 4 and 7. In laboratory studies, in the presence of goethite or illite, pyomelanin enhanced U sequestration by these minerals. Tyrosine amended soils in a field test demonstrated increased U sequestration capacity following pyomelanin production up to 13 months after tyrosine treatments

  1. Tracer kinetic modelling of receptor data with mathematical metabolite correction

    International Nuclear Information System (INIS)

    Burger, C.; Buck, A.

    1996-01-01

    Quantitation of metabolic processes with dynamic positron emission tomography (PET) and tracer kinetic modelling relies on the time course of authentic ligand in plasma, i.e. the input curve. The determination of the latter often requires the measurement of labelled metabilites, a laborious procedure. In this study we examined the possibility of mathematical metabolite correction, which might obviate the need for actual metabolite measurements. Mathematical metabilite correction was implemented by estimating the input curve together with kinetic tissue parameters. The general feasibility of the approach was evaluated in a Monte Carlo simulation using a two tissue compartment model. The method was then applied to a series of five human carbon-11 iomazenil PET studies. The measured cerebral tissue time-activity curves were fitted with a single tissue compartment model. For mathematical metabolite correction the input curve following the peak was approximated by a sum of three decaying exponentials, the amplitudes and characteristic half-times of which were then estimated by the fitting routine. In the simulation study the parameters used to generate synthetic tissue time-activity curves (K 1 -k 4 ) were refitted with reasonable identifiability when using mathematical metabolite correciton. Absolute quantitation of distribution volumes was found to be possible provided that the metabolite and the kinetic models are adequate. If the kinetic model is oversimplified, the linearity of the correlation between true and estimated distribution volumes is still maintained, although the linear regression becomes dependent on the input curve. These simulation results were confirmed when applying mathematical metabolite correction to the 11 C iomazenil study. Estimates of the distribution volume calculated with a measured input curve were linearly related to the estimates calculated using mathematical metabolite correction with correlation coefficients >0.990. (orig./MG)

  2. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    Science.gov (United States)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  3. Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    McMahon Louis

    2008-10-01

    Full Text Available Abstract Background It is known that following chronic dosing with bupropion HCl active metabolites are present in plasma at levels that are several times higher than that of the parent drug, but the possible convulsive effects of the major metabolites are not known. Methods We investigated the convulsive liability and dose-response of the three major bupropion metabolites following intraperitoneal administration of single doses in female Swiss albino mice, namely erythrohydrobupropion HCl, threohydrobupropion HCl, and hydroxybupropion HCl. We compared these to bupropion HCl. The actual doses of the metabolites administered to mice (n = 120; 10 per dose group were equimolar equivalents of bupropion HCl 25, 50 and 75 mg/kg. Post treatment, all animals were observed continuously for 2 h during which the number, time of onset, duration and intensity of convulsions were recorded. The primary outcome variable was the percentage of mice in each group who had a convulsion at each dose. Other outcome measures were the time to onset of convulsions, mean convulsions per mouse, and the duration and intensity of convulsions. Results All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg followed by threohydrobupropion HCl (50% and 100%, and then erythrohydrobupropion HCl (10% and 90%, compared to bupropion HCl (0% and 10%. Probit analysis also revealed the dose-response curves were significantly different (p 50 values of 35, 50, 61 and 82 mg/kg, respectively for the four different treatments. Cox proportional hazards model results showed that bupropion HCl, erythrohydrobupropion HCl, and threohydrobupropion HCl were significantly less likely to induce convulsions within the 2-h post treatment observation period compared to hydroxybupropion HCl. The

  4. The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi.

    Science.gov (United States)

    Ding, Chang-Hong; Wang, Qian-Bo; Guo, Shenglei; Wang, Zhen-Yue

    Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20d, and made spore concentration in co-culture medium was 1×10 4 mL -1 , after co-cultured for 12d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  5. Clinical applications of fast liquid chromatography: a review on the analysis of cardiovascular drugs and their metabolites.

    Science.gov (United States)

    Baranowska, Irena; Magiera, Sylwia; Baranowski, Jacek

    2013-05-15

    One of the major challenges facing the medicine today is developing new therapies that enhance human health. To help address these challenges the utilization of analytical technologies and high-throughput automated platforms has been employed; in order to perform more experiments in a shorter time frame with increased data quality. In the last decade various analytical strategies have been established to enhance separation speed and efficiency in liquid chromatography applications. Liquid chromatography is an increasingly important tool for monitoring drugs and their metabolites. Furthermore, liquid chromatography has played an important role in pharmacokinetics and metabolism studies at these drug development stages since its introduction. This paper provides an overview of current trends in fast chromatography for the analysis of cardiovascular drugs and their metabolites in clinical applications. Current trends in fast liquid chromatographic separations involve monolith technologies, fused-core columns, high-temperature liquid chromatography (HTLC) and ultra-high performance liquid chromatography (UHPLC). The high specificity in combination with high sensitivity makes it an attractive complementary method to traditional methodology used for routine applications. The practical aspects of, recent developments in and the present status of fast chromatography for the analysis of biological fluids for therapeutic drug and metabolite monitoring, pharmacokinetic studies and bioequivalence studies are presented. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Structure-activity relationships for the fluorescence of ochratoxin A: Insight for detection of ochratoxin A metabolites

    International Nuclear Information System (INIS)

    Frenette, Christine; Paugh, Robert J.; Tozlovanu, Mariana; Juzio, Maud; Pfohl-Leszkowicz, Annie; Manderville, Richard A.

    2008-01-01

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that is widely found as a contaminant of food products. The toxin is a renal carcinogen in male rats, the cause of mycotoxicoses in pigs and has been associated with chronic human kidney diseases. Bioactivation has been implicated in OTA-mediated toxicity, although inconsistent results have been reported, due, in part, to the difficulty in detecting OTA metabolites in vivo. Liquid chromatography (LC) coupled with fluorescence detection (FLD) is the most widely used analytical detection method for OTA. Under acidic conditions the toxin generates blue fluorescence (465 nm) that is due to an excited state intramolecular proton transfer (ESIPT) process that generates an emissive keto tautomer. Disruption of this ESIPT process quenches fluorescence intensity and causes a blue shift in emission maxima. The aim of the present study was to determine the impact of the C5-chlorine atom, the lactone moiety and the amide bond on OTA fluorescence and derive optical parameters for OTA metabolites that have been detected in vitro. Our results highlight the limitations of LC/FLD for OTA metabolites that do not undergo ESIPT. For emissive derivatives, our absorption and emission data improves the sensitivity of LC/FLD (3-4-fold increase in the limit of detection (LOD)) for OTA analogues bearing a C5-OH group, such as the hydroquinone (OTHQ) metabolite and the glutathione conjugate of OTA (OTA-GSH). This increased sensitivity may facilitate the detection of OTA metabolites bearing a C5-OH group in biological fluids and enhance our understanding of OTA-mediated toxicity

  7. Metabolites of polycyclic aromatic hydrocarbons (PAHs) in bile as biomarkers of pollution in European eel (Anguilla anguilla) from German rivers.

    Science.gov (United States)

    Nagel, F; Kammann, U; Wagner, C; Hanel, R

    2012-02-01

    In the light of the alarming decline of the European eel (Anguilla anguilla L.) population, there is an urgent need to define ecological indicators for eel habitat quality. Due to an increasing shortage of glass eels available for local stock enhancement, the decision of whether restocking is a valuable management tool to increase high-quality silver eel escapement to the sea needs to be evaluated. Organic contaminants, such as polycyclic aromatic hydrocarbons (PAHs), are among the major threats to fish in their habitat. Therefore, the aim of the investigation presented here was to examine metabolites of PAHs in eel bile as one possible marker for habitat quality. In total, 170 yellow eels were collected in the rivers Rhine, Ems, Weser, Elbe, Havel, Schlei, Eider, Trave, Warnow, Peene, Uecker, and Oder in 2009. PAH metabolites in eel bile were analyzed using high-performance liquid chromatography with fluorescence detection. Metabolites of pyrene and phenanthrene were investigated. Concentrations of PAH metabolites in eel bile varied significantly between several rivers, with the highest mean concentrations of 1-hydroxypyrene and 1-hydroxyphenanthrene in eel bile from the river Trave (2421 and 632 ng/ml). Moreover, huge differences in the ratio of 1-hydroxypyrene to 1-hydroxyphenanthrene, with the highest mean value in eel bile from the river Ems (7.43) and the lowest mean value in eel bile from the river Uecker (0.70), indicate different sources of PAH contamination. A comparative analysis of PAH-metabolite contamination of eels in different river systems is seen as a first step toward a classification of freshwater habitats for restocking purposes.

  8. Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Yong-Ping Lu

    2018-01-01

    Full Text Available Background/Aims: Gestational diabetes (GDM might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32: 1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM.

  9. Physiological characterization of secondary metabolite producing Penicillium cell factories

    DEFF Research Database (Denmark)

    Grijseels, Sietske; Nielsen, Jens; Nielsen, Jens

    2017-01-01

    Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order to facilit......Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order...... to facilitate the development of novel secondary metabolite producing processes, two routes are typically explored: optimization of the native producer or transferring the enzymatic pathway into a heterologous host. Recent genome sequencing of ten Penicillium species showed the vast amount of secondary...... metabolite gene clusters present in their genomes, and makes them accessible for rational strain improvement. In this study, we aimed to characterize the potential of these ten Penicillium species as native producing cell factories by testing their growth performance and secondary metabolite production...

  10. Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees.

    Science.gov (United States)

    Masi, Marco; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Scanu, Bruno; Evidente, Antonio; Cimmino, Alessio

    2018-01-01

    Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity. This review will highlight the goldmine of secondary metabolites produced by pathogenic and endophytic fungi of forest trees with focus on their biological activities. A structured search of bibliographic databases for peer-reviewed research literature was undertaken using a research discovery application providing access to a large and authoritative source of references. The papers selected were examined and the main results were reported and discussed. Two hundred forthy-one papers were included in the review, outlined a large number of secondary metabolites produced by pathogenic and endophiltic fungi and their biological activities, including phytotoxic, antifungal, antioomycetes, antibacterial, brine shrimp lethality, mosquito biting deterrence and larvicidal, cytotoxic, antiproliferative and many other bioactivities. The findings of this review confirm the importance of secondary metabolites produced by pathogenic and endophytic fungi from forest plants growing in temperate regions as an excellent prospects to discover compounds with new bioactivities and mode of actions. In addition, the potential of some metabolites as a source of new drugs and biopesticides is underlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Science.gov (United States)

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-01-01

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences. PMID:27275838

  12. Biodegradation of clofibric acid and identification of its metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setubal do Instituto Politecnico de Setubal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setubal (Portugal); Oehmen, A. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, G. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Noronha, J.P. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2012-11-30

    Graphical abstract: Metabolites produced during clofibric acid biodegradation. Highlights: Black-Right-Pointing-Pointer Clofibric acid is biodegradable. Black-Right-Pointing-Pointer Mainly heterotrophic bacteria degraded the clofibric acid. Black-Right-Pointing-Pointer Metabolites of clofibric acid biodegradation were identified. Black-Right-Pointing-Pointer The metabolic pathway of clofibric acid biodegradation is proposed. - Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration = 2 mg L{sup -1}), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including {alpha}-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. {alpha}-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study.

  13. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-09-01

    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  14. [Systems biology applications to explore secondary metabolites in medicinal plants].

    Science.gov (United States)

    Huang, Luqi; Gao, Wei; Zhou, Jie; Wang, Ruiting

    2010-01-01

    Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically.

  15. Some Metabolites Act as Second Messengers in Yeast Chronological Aging

    Directory of Open Access Journals (Sweden)

    Karamat Mohammad

    2018-03-01

    Full Text Available The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast Saccharomyces cerevisiae. These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally. Here, we analyze mechanisms through which the spatiotemporal dynamics of changes in the concentrations of the key metabolites influence yeast chronological lifespan. Our analysis indicates that a distinct set of metabolites can act as second messengers that define the pace of yeast chronological aging. Molecules that can operate both as intermediates of yeast metabolism and as second messengers of yeast chronological aging include reduced nicotinamide adenine dinucleotide phosphate (NADPH, glycerol, trehalose, hydrogen peroxide, amino acids, sphingolipids, spermidine, hydrogen sulfide, acetic acid, ethanol, free fatty acids, and diacylglycerol. We discuss several properties that these second messengers of yeast chronological aging have in common with second messengers of signal transduction. We outline how these second messengers of yeast chronological aging elicit changes in cell functionality and viability in response to changes in the nutrient, energy, stress, and proliferation status of the cell.

  16. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Laura Scheffler

    2016-06-01

    Full Text Available The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O, as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2. Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  17. Flavonoid metabolites transport across a human BBB model.

    Science.gov (United States)

    Faria, Ana; Meireles, Manuela; Fernandes, Iva; Santos-Buelga, Celestino; Gonzalez-Manzano, Susana; Dueñas, Montserrat; de Freitas, Victor; Mateus, Nuno; Calhau, Conceição

    2014-04-15

    This study aimed to evaluate the transmembrane transport of different flavonoids (flavan-3-ols, anthocyanins and flavonols) and some of their metabolites (methylated and conjugated with glucuronic acid) across hCMEC/D3 cells (a blood-brain barrier (BBB) model). Further metabolism of the tested compounds was assayed and their transport modulated in an attempt to elucidate the mechanisms behind this process. The transport across hCMEC/D3 cells was monitored in basolateral media at 1, 3 and 18 h by HPLC-DAD/MS. All the flavonoids and their metabolites were transported across hCMEC/D3 cells in a time-dependent manner. In general, the metabolites showed higher transport efficiency than the native flavonoid. No further biotransformation of the metabolites was found as consequence of cellular metabolism. Anthocyanins and their metabolites crossed this BBB cell model in a lipophilicity-dependent way. Quercetin transport was influenced by phosphatase modulators, suggesting a phosphorylation/dephosphorylation regulation mechanism. Overall, this work suggests that flavonoids are capable of crossing the BBB and reaching the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Metabolite identification and molecular fingerprint prediction through machine learning.

    Science.gov (United States)

    Heinonen, Markus; Shen, Huibin; Zamboni, Nicola; Rousu, Juho

    2012-09-15

    Metabolite identification from tandem mass spectra is an important problem in metabolomics, underpinning subsequent metabolic modelling and network analysis. Yet, currently this task requires matching the observed spectrum against a database of reference spectra originating from similar equipment and closely matching operating parameters, a condition that is rarely satisfied in public repositories. Furthermore, the computational support for identification of molecules not present in reference databases is lacking. Recent efforts in assembling large public mass spectral databases such as MassBank have opened the door for the development of a new genre of metabolite identification methods. We introduce a novel framework for prediction of molecular characteristics and identification of metabolites from tandem mass spectra using machine learning with the support vector machine. Our approach is to first predict a large set of molecular properties of the unknown metabolite from salient tandem mass spectral signals, and in the second step to use the predicted properties for matching against large molecule databases, such as PubChem. We demonstrate that several molecular properties can be predicted to high accuracy and that they are useful in de novo metabolite identification, where the reference database does not contain any spectra of the same molecule. An Matlab/Python package of the FingerID tool is freely available on the web at http://www.sourceforge.net/p/fingerid. markus.heinonen@cs.helsinki.fi.

  19. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions.

    Science.gov (United States)

    Jančič, Sašo; Frisvad, Jens C; Kocev, Dragi; Gostinčar, Cene; Džeroski, Sašo; Gunde-Cimerman, Nina

    2016-01-01

    The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A and UCA 1064-B). In particular an increase in NaCl concentration from 5% to 15% in the growth media increased the production of the toxic metabolites wallimidione, walleminol and walleminone.

  20. In vivo MRS metabolite quantification using genetic optimization

    Science.gov (United States)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; van Ormondt, D.; Graveron-Demilly, D.

    2011-11-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure.

  1. In vivo MRS metabolite quantification using genetic optimization

    International Nuclear Information System (INIS)

    Papakostas, G A; Mertzios, B G; Karras, D A; Van Ormondt, D; Graveron-Demilly, D

    2011-01-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure

  2. Discovery of novel secondary metabolites in Aspergillus aculeatus

    DEFF Research Database (Denmark)

    Petersen, Lene Maj; Holm, Dorte Koefoed; Gotfredsen, Charlotte Held

    2012-01-01

    Polyketides (PKs) and non-ribosomal peptides (NRPs) constitute large classes of diverse secondary metabolites (SMs) and are important sources for pharmaceuticals due to their structural diversity and wide variety of biological activities. Our investigation of the chemical profile of the industria......Polyketides (PKs) and non-ribosomal peptides (NRPs) constitute large classes of diverse secondary metabolites (SMs) and are important sources for pharmaceuticals due to their structural diversity and wide variety of biological activities. Our investigation of the chemical profile......, whereby several novel secondary metabolites have been discovered. A. aculeatus has recently been genome-sequenced; however no genetic approaches have so far been described to facilitate genetic engineering. We here present a system for non-integrated (AMA1-based) gene expression in A. aculeatus based...

  3. Plants and endophytes: equal partners in secondary metabolite production?

    Science.gov (United States)

    Ludwig-Müller, Jutta

    2015-07-01

    Well known plant production systems should be re-evaluated due to findings that the interesting metabolite might actually be produced by microbes intimately associated with the plant, so-called endophytes. Endophytes can be bacteria or fungi and they are characterized usually by the feature that they do not cause any harm to the host. Indeed, in some cases, such as mycorrhizal fungi or other growth promoting endophytes, they can be beneficial for the plant. Here some examples are reviewed where the host plant and/or endophyte metabolism can be induced by the other partner. Also, partial or complete biosynthesis pathways for plant secondary metabolites can be attributed to such endophytes. In other cases the host plant is able to metabolize substances from fungal origin. The question of the natural role of such metabolic changes for the endophyte will be briefly touched. Finally, the consequences for the use of plant cultures for secondary metabolite production is discussed.

  4. Intact penetratin metabolite permeates across Caco-2 monolayers

    DEFF Research Database (Denmark)

    Birch, Ditlev; Christensen, Malene Vinther; Stærk, Dan

    . Previous studies have demonstrated that cell-penetrating peptides (CPPs) may be used as carriers in order to improve the bioavailability of a therapeutic cargo like insulin after oral administration. Penetratin, a commonly used CPP, has been shown to increase the uptake of insulin across Caco-2 cell......, the aim of the present study was to investigate penetratin metabolites with respect to effects on cellular viability, their epithelial permeation and cell uptake. Methods Extracellular and intracellular degradation of penetratin was assessed by incubation of the carrier peptide on the apical side of Caco......-2 cells cultured on permeable filter inserts and in cell lysates, respectively. The epithelial permeation of penetratin and the formed metabolites was assessed by using Caco-2 monolayers cultured on permeable filter inserts. Results Preliminary data revealed that at least one specific metabolite...

  5. Plant secondary metabolite profiling evidences strain-dependent effect in the Azospirillum-Oryza sativa association.

    Science.gov (United States)

    Chamam, Amel; Sanguin, Hervé; Bellvert, Floriant; Meiffren, Guillaume; Comte, Gilles; Wisniewski-Dyé, Florence; Bertrand, Cédric; Prigent-Combaret, Claire

    2013-03-01

    Azospirillum is a plant growth-promoting rhizobacterium (PGPR) able to enhance growth and yield of cereals such as rice, maize and wheat. The growth-promoting ability of some Azospirillum strains appears to be highly specific to certain plant species and cultivars. In order to ascertain the specificity of the associative symbiosis between rice and Azospirillum, the physiological response of two rice cultivars, Nipponbare and Cigalon, inoculated with two rice-associated Azospirillum was analyzed at two levels: plant growth response and plant secondary metabolic response. Each strain of Azospirillum (Azospirillum lipoferum 4B isolated from Cigalon and Azospirillum sp. B510 isolated from Nipponbare) preferentially increased growth of the cultivar from which it was isolated. This specific effect is not related to a defect in colonization of host cultivar as each strain colonizes effectively both rice cultivars, either at the rhizoplane (for 4B and B510) and inside the roots (for B510). The metabolic profiling approach showed that, in response to PGPR inoculation, profiles of rice secondary metabolites were modified, with phenolic compounds such as flavonoids and hydroxycinnamic derivatives being the main metabolites affected. Moreover, plant metabolic changes differed according to Azospirillum strain×cultivar combinations; indeed, 4B induced major secondary metabolic profile modifications only on Cigalon roots, while B510, probably due to its endophytic feature, induced metabolic variations on shoots and roots of both cultivars, triggering a systemic response. Plant secondary metabolite profiling thereby evidences the specific interaction between an Azospirillum strain and its original host cultivar. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease.

    Science.gov (United States)

    Cosola, Carmela; Rocchetti, Maria Teresa; Cupisti, Adamasco; Gesualdo, Loreto

    2018-04-01

    In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design

  7. Elucidating the Biological Basis for the Reinforcing Actions of Alcohol in the Mesolimbic Dopamine System: The Role of Active Metabolites of Alcohol

    Directory of Open Access Journals (Sweden)

    Gerald A Deehan

    2013-08-01

    Full Text Available The development of successful pharmacotherapeutics for the treatment of alcoholism is predicated upon understanding the biological action of alcohol. A limitation of the alcohol research field has been examining the effects of alcohol only and ignoring the multiple biological active metabolites of alcohol. The concept that alcohol is a ‘pro-drug’ is not new. Alcohol is readily metabolized to acetaldehyde within the brain. Acetaldehyde is a highly reactive compound that forms a number of condensation products, including salsolinol and iso-salsolinol (acetaldehyde and dopamine. Recent experiments have established that numerous metabolites of ethanol do have direct CNS action, and could, in part or whole, mediate the reinforcing actions of alcohol within the mesolimbic dopamine system. The mesolimbic dopamine system originates in the ventral tegmental area (VTA and projects to forebrain regions that include the nucleus accumbens (Acb and the medial prefrontal cortex (mPFC and is thought to be the neurocircuitry governing the rewarding properties of drugs of abuse. Within this neurocircuitry there is convincing evidence that; 1 biologically active metabolites of alcohol can directly or indirectly increase the activity of VTA dopamine neurons, 2 alcohol and alcohol metabolites are reinforcing within the mesolimbic dopamine system, 3 inhibiting the alcohol metabolic pathway inhibits the biological consequences of alcohol exposure, 4 alcohol consumption can be reduced by inhibiting/attenuating the alcohol metabolic pathway in the mesolimbic dopamine system, 5 alcohol metabolites can alter neurochemical levels within the mesolimbic dopamine system, and 6 alcohol interacts with alcohol metabolites to enhance the actions of both compounds. The data indicate that there is a positive relationship between alcohol and alcohol metabolites in regulating the biological consequences of consuming alcohol and the potential of alcohol use escalating to

  8. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  9. Quantitative Method for Simultaneous Analysis of Acetaminophen and 6 Metabolites.

    Science.gov (United States)

    Lammers, Laureen A; Achterbergh, Roos; Pistorius, Marcel C M; Romijn, Johannes A; Mathôt, Ron A A

    2017-04-01

    Hepatotoxicity after ingestion of high-dose acetaminophen [N-acetyl-para-aminophenol (APAP)] is caused by the metabolites of the drug. To gain more insight into factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP and its most important metabolites. However, these methods require a comprehensive sample preparation and long run times. The aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of acetaminophen, the main metabolites acetaminophen glucuronide and acetaminophen sulfate, and 4 Cytochrome P450-mediated metabolites by using liquid chromatography with mass spectrometric (LC-MS) detection. The method was developed and validated for the human plasma, and it entailed a single method for sample preparation, enabling quick processing of the samples followed by an LC-MS method with a chromatographic run time of 9 minutes. The method was validated for selectivity, linearity, accuracy, imprecision, dilution integrity, recovery, process efficiency, ionization efficiency, and carryover effect. The method showed good selectivity without matrix interferences. For all analytes, the mean process efficiency was >86%, and the mean ionization efficiency was >94%. Furthermore, the accuracy was between 90.3% and 112% for all analytes, and the within- and between-run imprecision were method presented here enables the simultaneous quantification of APAP and 6 of its metabolites. It is less time consuming than previously reported methods because it requires only a single and simple method for the sample preparation followed by an LC-MS method with a short run time. Therefore, this analytical method provides a useful method for both clinical and research purposes.

  10. Urinary glucocorticoid metabolites: biomarkers to classify adrenal incidentalomas?

    Science.gov (United States)

    Brossaud, Julie; Ducint, Dominique; Corcuff, Jean-Benoît

    2015-01-08

    Total urinary cortisol metabolites represent cortisol production and metabolism. We hypothesized that to assay metabolites could add some information to the one provided by a sole cortisol assay. We set up an inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites. We investigated 43 patients with benign secreting (AT+) or silent (AT-) adrenal tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients with a Cushing's disease (CD). The initial investigation included immunoreactive quantification of urinary free cortisol (UFC). Cortisol metabolites were overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a control population (Ctl). Cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE) excretions were significantly increased in AT compared to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression retaining cortisol, THF, and α- and β-cortolone as significant analytes allowed the construction of a receiver-operating characteristics (ROC) curve significantly better than the curve generated by cortisol alone (area under the curve (AUC) 0·927 vs 0·729, respectively; P < 0·0001). More importantly, although there was no significant difference between Ctl vs AT- subjects for cortisol metabolites, a logistic regression retaining cortisol, allo-THF, and α- and β-cortolone as significant analytes generated a ROC curve performing significantly better than cortisol alone (AUC 0·910 vs 0·635, respectively; P < 0·0001). Cortisol metabolite excretion is modified in AT, including AT-, patients even without modification of UFC. Clinical usefulness of these biomarkers has to be investigated in prospective studies following up patients with AT. © 2015 John Wiley & Sons Ltd.

  11. Twins labeling-liquid chromatography/mass spectrometry based metabolomics for absolute quantification of tryptophan and its key metabolites.

    Science.gov (United States)

    Guo, Huimin; Jiao, Yu; Wang, Xu; Lu, Tao; Zhang, Zunjian; Xu, Fengguo

    2017-06-30

    Tryptophan metabolism plays a crucial role in mediating gastrointestinal function. Here, in order to absolutely quantify tryptophan and its metabolites, a liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics approach was developed using N-dimethyl-/N-diethyl-amino naphthalene-1-sulfonyl chloride (Dns/Dens-Cl) as twins labeling (TL) reagents. Dns-Cl is famous in amine and phenol derivations, and structure is similar with Dens-Cl. The introduction of easily protonated moiety of tertiary ammonium-containing part in the derivatives from Dns to tryptophan and its metabolites not only improved the LC separation but also enhanced their MS response. In addition, the Dens labeled standards were used as internal standards to compensate for matrix effects and ensure accurate quantifications. With the proposed method, twelve metabolites in tryptophan pathway could be detected at sub-ng/mL levels using only 20μL rat serum (the limit of detection could reach 3pg/mL for tryptamine, N-acetyl-serotonin and 6-hydroxymelatonin). The sensitivity was enhanced about 1-2 orders of magnitude compared with non-derivatization method. Focusing on tryptophan pathway, the method was successfully applied to determine the absolute serum concentrations of twelve tryptophan metabolites in a vincristine-induced ileus rat model. A significant down-regulation of the tryptophan metabolism along the kynurenine pathway and up-regulation of serotonin pathway were uncovered. Our findings provide a deeper insight into the mechanism of gastrointestinal dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. IN SITU URANIUM STABILIZATION BY MICROBIAL METABOLITES

    Energy Technology Data Exchange (ETDEWEB)

    Turick, C; Anna Knox, A; Chad L Leverette,C; Yianne Kritzas, Y

    2006-11-29

    Soil contaminated with U was the focus of this study in order to develop in-situ, U bio-immobilization technology. We have demonstrated microbial production of a metal chelating biopolymer, pyomelanin, in U contaminated soil from the Tims Branch area of the Department of Energy (DOE) Savannah River Site (SRS) as a result of tyrosine amendments. Bacterial densities of pyomelanin producers were >106 cells/g wet soil. Pyomelanin demonstrated U chelating and mineral binding capacities at pH 4 and 7. In laboratory studies, in the presence of goethite or illite, pyomelanin enhanced U sequestration by these minerals. Tyrosine amended soils in field tests demonstrated increased U sequestration capacity following pyomelanin production up to 13 months after tyrosine treatments.

  13. Biomarker Research in Parkinson's Disease Using Metabolite Profiling

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Heegaard, Niels H H; Færgeman, Nils J K

    2017-01-01

    Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD......., the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan...

  14. Diversity of secondary metabolites from Genus Artocarpus (Moraceae

    Directory of Open Access Journals (Sweden)

    ALIEFMAN HAKIM

    2010-11-01

    Full Text Available Hakim A. 2010. The diversity of secondary metabolites from Genus Artocarpus (Moraceae. Nusantara Bioscience 2:146-156. Several species of the Artocarpus genus (Moraceae have been investigated their natural product. The secondary metabolites successfully being isolatad from Artocarpus genus consist of terpenoid, flavonoids, stilbenoid, arylbenzofuran, neolignan, and adduct Diels-Alder. Flavonoid group represent the compound which is the most found from Artocarpus plant. The flavonoids compound which are successfully isolated from Artocarpus plant consist of the varied frameworks like chalcone, flavanone, flavan-3-ol, simple flavone, prenylflavone, oxepinoflavone, pyranoflavone, dihydrobenzoxanthone, furanodihydrobenzoxanthone, pyranodihydrobenzoxanthone, quinonoxanthone, cyclopentenoxanthone, xanthonolide, dihydroxanthone.

  15. Urinary excretion of MPTP and its primary metabolites in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lau, Y.S.; Crampton, J.M.; Wilson, J.A.

    1988-01-01

    Mice were injected with single doses of MPTP containing one ..mu..Ci of (/sup 3/H)methyl-MPTP. Approximately 42% of the total injected (/sup 3/H) was detected in the urine within 3 hours after drug administration. The early urine samples were analyzed using high pressure liquid chromatography. MPTP N-oxide was identified as a major metabolite, with trace amounts of MPP/sup +/ and MPTP also detected. The urinary volume and excretion of MPTP metabolites were inhibited by pretreating the animals with probenecid. The results indicate that large amounts of injected MPTP are rapidly metabolized in the periphery by liver enzymes to form MPTP N-oxide.

  16. Pathway elucidation and metabolic engineering of specialized plant metabolites

    DEFF Research Database (Denmark)

    Salomonsen, Bo

    A worldwide need to liberate ourselves from unsustainable petrochemicals has led to numerous metabolic engineering projects, mostly carried out in microbial hosts. Using systems biology for predicting and altering the metabolism of microorganisms towards production of a desired metabolite...... and fluxomics for a considerable number of organisms. Unfortunately, transferring the wealth of data to valuable information for metabolic engineering purposes is a non-obvious task. This PhD thesis describes a palate of tools used in generation of cell factories for production of specialized plant metabolites...

  17. Production of bioactive secondary metabolites by marine Vibrionaceae

    DEFF Research Database (Denmark)

    Månsson, Maria; Gram, Lone; Larsen, Thomas Ostenfeld

    2011-01-01

    for their ability to produce bioactive secondary metabolites and studies have been limited to only a few species. Most of the compounds isolated from vibrios so far are non-ribosomal peptides or hybrids thereof, with examples of N-containing compounds produced independent of nonribosomal peptide synthetases (NRPS...... also been isolated from other distantly related bacteria. This cosmopolitan occurrence of metabolites indicates a high incidence of horizontal gene transfer, which raises interesting questions concerning the ecological function of some of these molecules. This account underlines the pending potential...

  18. Sulfate Metabolites of 4-Monochlorobiphenyl in Whole Poplar Plants

    OpenAIRE

    Zhai, Guangshu; Lehmler, Hans-Joachim; Schnoor, Jerald L.

    2012-01-01

    4-Monochlorobiphenyl (PCB3) has been proven to be transformed into hydroxylated metabolites of PCB3 (OH-PCB3s) in whole poplar plants in our previous work. However, hydroxylated metabolites of PCBs, including OH-PCB3s, as the substrates of sulfotransferases have not been studied in many organisms including plants in vivo. Poplar (Populus deltoides × nigra, DN34) was used to investigate the further metabolism from OH-PCB3s to PCB3 sulfates because it is a model plant and one that is frequently...

  19. Fermented functional foods based on probiotics and their biogenic metabolites.

    Science.gov (United States)

    Stanton, Catherine; Ross, R Paul; Fitzgerald, Gerald F; Van Sinderen, Douwe

    2005-04-01

    The claimed health benefits of fermented functional foods are expressed either directly through the interaction of ingested live microorganisms, bacteria or yeast with the host (probiotic effect) or indirectly as a result of ingestion of microbial metabolites produced during the fermentation process (biogenic effect). Although still far from fully understood, several probiotic mechanisms of action have been proposed, including competitive exclusion, competition for nutrients and/or stimulation of an immune response. The biogenic properties of fermented functional foods result from the microbial production of bioactive metabolites such as certain vitamins, bioactive peptides, organic acids or fatty acids during fermentation.

  20. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close...... to and below the critical PO2] for two days caused large decreases in plasma nitrite and nitrate, which suggests reduced NOS activity and increased nitrite/nitrate utilization or loss. Tissue NO metabolites were largely maintained at their tissue-specific values under hypoxia, pointing at nitrite transfer from...

  1. Dissection of Trichoderma longibrachiatum-induced defense in onion (Allium cepa L.) against Fusarium oxysporum f. sp. cepa by target metabolite profiling.

    Science.gov (United States)

    Abdelrahman, Mostafa; Abdel-Motaal, Fatma; El-Sayed, Magdi; Jogaiah, Sudisha; Shigyo, Masayoshi; Ito, Shin-ichi; Tran, Lam-Son Phan

    2016-05-01

    Trichoderma spp. are versatile opportunistic plant symbionts that can cause substantial changes in the metabolism of host plants, thereby increasing plant growth and activating plant defense to various diseases. Target metabolite profiling approach was selected to demonstrate that Trichoderma longibrachiatum isolated from desert soil can confer beneficial agronomic traits to onion and induce defense mechanism against Fusarium oxysporum f. sp. cepa (FOC), through triggering a number of primary and secondary metabolite pathways. Onion seeds primed with Trichoderma T1 strain displayed early seedling emergence and enhanced growth compared with Trichoderma T2-treatment and untreated control. Therefore, T1 was selected for further investigations under greenhouse conditions, which revealed remarkable improvement in the onion bulb growth parameters and resistance against FOC. The metabolite platform of T1-primed onion (T1) and T1-primed onion challenged with FOC (T1+FOC) displayed significant accumulation of 25 abiotic and biotic stress-responsive metabolites, representing carbohydrate, phenylpropanoid and sulfur assimilation metabolic pathways. In addition, T1- and T1+FOC-treated onion plants showed discrete antioxidant capacity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) compared with control. Our findings demonstrated the contribution of T. longibrachiatum to the accumulation of key metabolites, which subsequently leads to the improvement of onion growth, as well as its resistance to oxidative stress and FOC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Biosynthesis of secondary metabolites in sugarcane

    Directory of Open Access Journals (Sweden)

    S.C. França

    2001-12-01

    Full Text Available A set of genes related to secondary metabolism was extracted from the sugarcane expressed sequence tag (SUCEST database and was used to investigate both the gene expression pattern of key enzymes regulating the main biosynthetic secondary metabolism pathways and the major classes of metabolites involved in the response of sugarcane to environmental and developmental cues. The SUCEST database was constructed with tissues in different physiological conditions which had been collected under varied situation of environmental stress. This database allows researchers to identify and characterize the expressed genes of a wide range of putative enzymes able to catalyze steps in the phenylpropanoid, isoprenoid and other pathways of the special metabolic mechanisms involved in the response of sugarcane to environmental changes. Our results show that sugarcane cDNAs encoded putative ultra-violet induced sesquiterpene cyclases (SC; chalcone synthase (CHS, the first enzyme in the pathway branch for flavonoid biosynthesis; isoflavone synthase (IFS, involved in plant defense and root nodulation; isoflavone reductase (IFR, a key enzyme in phenylpropanoid phytoalexin biosynthesis; and caffeic acid-O-methyltransferase, a key enzyme in the biosynthesis of lignin cell wall precursors. High levels of CHS transcripts from plantlets infected with Herbaspirillum rubri or Gluconacetobacter diazotroficans suggests that agents of biotic stress can elicit flavonoid biosynthesis in sugarcane. From this data we have predicted the profile of isoprenoid and phenylpropanoid metabolism in sugarcane and pointed the branches of secondary metabolism activated during tissue-specific stages of development and the adaptive response of sugarcane to agents of biotic and abiotic stress, although our assignment of enzyme function should be confirmed by careful biochemical and genetic supporting evidence.Este trabalho foi realizado com os objetivos de gerar uma coleção de genes

  3. Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

    Directory of Open Access Journals (Sweden)

    Ashish Srivastava

    2017-07-01

    Full Text Available A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L. plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV and Ageratum leaf curl betasatellite (ALCB, respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.

  4. Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre type.

    Directory of Open Access Journals (Sweden)

    Juan Li

    Full Text Available The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age were measured. Multivariate statistical analysis of plasma metabolite profiles demonstrated effects of development and genotype but not gender. Plasma from Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a metabolic profile consistent with contributions from the affected hypertrophic fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue. We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.

  5. Adjustment of metabolite composition in the haemolymph to seasonal variations in the land snail Helix pomatia.

    Science.gov (United States)

    Nicolai, Annegret; Filser, Juliane; Lenz, Roman; Bertrand, Carole; Charrier, Maryvonne

    2011-05-01

    In temperate regions, land snails are subjected to subzero temperatures in winter and hot temperatures often associated to drought in summer. The response to these environmental factors is usually a state of inactivity, hibernation and aestivation, respectively, in a temperature and humidity buffered refuge, accompanied by physiological adjustments to resist cold or heat stress. We investigated how environmental factors in the microhabitat and body condition influence the metabolite composition of haemolymph of the endangered species Helix pomatia. We used UPLC and GC-MS techniques and analyzed annual biochemical variations in a multivariate model. Hibernation and activity months differed in metabolite composition. Snails used photoperiod as cue for seasonal climatic variations to initiate a physiological state and were also highly sensitive to temperature variations, therefore constantly adjusting their physiological processes. Galactose levels gave evidence for the persistence of metabolic activity with energy expenditure during hibernation and for high reproductive activity in June. Triglycerides accumulated prior to hibernation might act as cryoprotectants or energy reserves. During the last month of hibernation snails activated physiological processes related to arousal. During activity, protein metabolism was reflected by high amino acid level. An exceptional aestivation period was observed in April giving evidence for heat stress responses, like the protection of cells from dehydration by polyols and saccharides, the membrane stabilization by cholesterol and enhanced metabolism using the anaerobic succinic acid pathway to sustain costly stress responses. In conclusion, physiological adjustments to environmental variations in Helix pomatia involve water loss regulation, cryoprotectant or heatprotectant accumulation.

  6. Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes.

    Science.gov (United States)

    González-Menéndez, Víctor; Pérez-Bonilla, Mercedes; Pérez-Victoria, Ignacio; Martín, Jesús; Muñoz, Francisca; Reyes, Fernando; Tormo, José R; Genilloud, Olga

    2016-02-18

    Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs) involved in their adaptation and survival within higher plants. The plant-microbe interaction may influence the expression of some biosynthetic pathways, otherwise cryptic in these fungi when grown in vitro. The aim of this study was to setup a systematic approach to evaluate and identify the possible effects of HDAC and DNMT inhibitors on the metabolic profiles of wild type fungal endophytes, including the chemical identification and characterization of the most significant SMs induced by these epigenetic modifiers.

  7. Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes

    Directory of Open Access Journals (Sweden)

    Víctor González-Menéndez

    2016-02-01

    Full Text Available Small molecule histone deacetylase (HDAC and DNA methyltransferase (DNMT inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs involved in their adaptation and survival within higher plants. The plant-microbe interaction may influence the expression of some biosynthetic pathways, otherwise cryptic in these fungi when grown in vitro. The aim of this study was to setup a systematic approach to evaluate and identify the possible effects of HDAC and DNMT inhibitors on the metabolic profiles of wild type fungal endophytes, including the chemical identification and characterization of the most significant SMs induced by these epigenetic modifiers.

  8. Phenolic metabolites in carnivorous plants: Inter-specific comparison and physiological studies.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj; Repčáková, Klára

    2012-03-01

    Despite intensive phytochemical research, data related to the accumulation of phenols in carnivorous plants include mainly qualitative reports. We have quantified phenolic metabolites in three species: Drosera capensis, Dionaea muscipula and Nepenthes anamensis in the "leaf" (assimilatory part) and the "trap" (digestive part). For comparison, commercial green tea was analysed. Phenylalanine ammonia-lyase (PAL) activities in Dionaea and Nepenthes were higher in the trap than in the leaf while the opposite was found in Drosera. Soluble phenols and majority of phenolic acids were mainly accumulated in the trap among species. Flavonoids were abundant in Drosera and Dionaea traps but not in Nepenthes. Phenolic acids were preferentially accumulated in a glycosidically-bound form and gallic acid was the main metabolite. Green tea contained more soluble phenols and phenolic acids but less quercetin. In vitro experiments with Drosera spathulata revealed that nitrogen deficiency enhances PAL activity, accumulation of phenols and sugars while PAL inhibitor (2-aminoindane-2-phosphonic acid) depleted phenols and some amino acids (but free phenylalanine and sugars were elevated). Possible explanations in physiological, biochemical and ecological context are discussed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Metabolite profiling at the cellular and subcellular level reveals metabolites associated with salinity tolerance in sugar beet.

    Science.gov (United States)

    Hossain, M Sazzad; Persicke, Marcus; ElSayed, Abdelaleim Ismail; Kalinowski, Jörn; Dietz, Karl-Josef

    2017-12-16

    Sugar beet is among the most salt-tolerant crops. This study aimed to investigate the metabolic adaptation of sugar beet to salt stress at the cellular and subcellular levels. Seedlings were grown hydroponically and subjected to stepwise increases in salt stress up to 300 mM NaCl. Highly enriched fractions of chloroplasts were obtained by non-aqueous fractionation using organic solvents. Total leaf metabolites and metabolites in chloroplasts were profiled at 3 h and 14 d after reaching the maximum salinity stress of 300 mM NaCl. Metabolite profiling by gas chromatography-mass spectrometry (GC-MS) resulted in the identification of a total of 83 metabolites in leaves and chloroplasts under control and stress conditions. There was a lower abundance of Calvin cycle metabolites under salinity whereas there was a higher abundance of oxidative pentose phosphate cycle metabolites such as 6-phosphogluconate. Accumulation of ribose-5-phosphate and ribulose-5-phosphate coincided with limitation of carbon fixation by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Increases in glycolate and serine levels indicated that photorespiratory metabolism was stimulated in salt-stressed sugar beet. Compatible solutes such as proline, mannitol, and putrescine accumulated mostly outside the chloroplasts. Within the chloroplast, putrescine had the highest relative level and probably assisted in the acclimation of sugar beet to high salinity stress. The results provide new information on the contribution of chloroplasts and the extra-chloroplast space to salinity tolerance via metabolic adjustment in sugar beet. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  10. Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites.

    Science.gov (United States)

    Hansson, Annelie; Knych, Heather; Stanley, Scott; Berndtson, Emma; Jackson, Liora; Bondesson, Ulf; Thevis, Mario; Hedeland, Mikael

    2018-02-01

    LGD-4033 has been found in human doping control samples and has the potential for illicit use in racehorses as well. It belongs to the pharmacological class of selective androgen receptor modulators (SARMs) and can stimulate muscle growth, much like anabolic steroids. However, SARMs have shown superior side effect profiles compared to anabolic steroids, which arguably makes them attractive for use by individuals seeking an unfair advantage over their competitors. The purpose of this study was to investigate the metabolites formed from LGD-4033 in the horse in order to find suitable analytical targets for doping controls. LGD-4033 was administered to three horses after which plasma and urine samples were collected and analyzed for metabolites using ultra high performance liquid chromatography coupled to a high resolution mass spectrometer. In horse urine, eight metabolites, both phase I and phase II, were observed most of which had not been described in other metabolic systems. Six of these were also detected in plasma. The parent compound was detected in plasma, but not in non-hydrolyzed urine. The longest detection times were observed for unchanged LGD-4033 in plasma and in urine hydrolyzed with β-glucuronidase and is thus suggested as the analytical target for doping control in the horse. The metabolite profile determined in the horse samples was also compared to those of human urine and fungal incubate from Cunninghamella elegans. The main human metabolite, dihydroxylated LGD-4033, was detected in the horse samples and was also produced by the fungus. However, it was a not a major metabolite for horse and fungus, which highlights the importance of performing metabolism studies in the species of interest. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The secondary metabolite bioinformatics portal: Computational tools to facilitate synthetic biology of secondary metabolite production

    Directory of Open Access Journals (Sweden)

    Tilmann Weber

    2016-06-01

    Full Text Available Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work. In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http://www.secondarymetabolites.org is introduced to provide a one-stop catalog and links to these bioinformatics resources. In addition, an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.

  12. Metabolite profiling reveals abiotic stress tolerance in Tn5 mutant of Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Vasvi Chaudhry

    stress tolerant metabolites from the NBRI1108T suggest that Tn5 mutagenesis enhanced tolerance towards high temperature and drought. Tolerance to drought was further confirmed in greenhouse experiments with maize as host plant, where NBRI1108T showed relatively high biomass under drought conditions.

  13. Protein adduct formation by glucuronide metabolites of permethrin

    NARCIS (Netherlands)

    Noort, D.; Zuylen, A. van; Fidder, A.; Ommen, B. van; Hulst, A.G.

    2008-01-01

    Biomonitoring of exposure to the insecticide permethrin is usually performed by analysis of its urinary metabolites 3-phenoxybenzoic acid (3-PBA) or cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Cl2CA). We are engaged in the development of a methodology to assess the

  14. Bioactive secondary metabolites with multiple activities from a fungal endophyte

    NARCIS (Netherlands)

    Bogner, C.W.; Kamdem, R.S.; Stichtermann, G.; Matthäus, C.; Hölscher, D.; Popp, J.; Proksch, P.; Grundler, F.M.; Schouten, A.

    2017-01-01

    In order to replace particularly biohazardous nematocides, there is a strong drive to finding natural product-based alternatives with the aim of containing nematode pests in agriculture. The metabolites produced by the fungal endophyte Fusarium oxysporum 162 when cultivated on rice media were

  15. Antioxidant status, immune system, blood metabolites and carcass ...

    African Journals Online (AJOL)

    This experiment was conducted to evaluate the effects of dietary turmeric rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of organs in pre and post heat stressed broilers. Two hundred and sixty-four (264) day-old male Arian broiler chicks were randomly ...

  16. Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine.

    Science.gov (United States)

    Guo, Xiucai; Lin, Dongju; Li, Weiwei; Wang, Kai; Peng, Ying; Zheng, Jiang

    2016-03-21

    Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10-DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ.

  17. (1) H-MRS processing parameters affect metabolite quantification

    DEFF Research Database (Denmark)

    Bhogal, Alex A; Schür, Remmelt R; Houtepen, Lotte C

    2017-01-01

    Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification....... reinforce the notion that standard practices should be established to regularize outcomes of (1) H-MRS studies, and that basis sets used for processing should be made available to the scientific community....... individualized and optimal parameter settings using LCModel software. Data were processed a second time in one group using an independent software package (NMRWizard) for an additional comparison with a different post-processing platform. Correlations across research groups of the ratio between the highest and...... + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results...

  18. Metabonomics identifies serum metabolite markers of colorectal cancer.

    Science.gov (United States)

    Tan, Binbin; Qiu, Yunping; Zou, Xia; Chen, Tianlu; Xie, Guoxiang; Cheng, Yu; Dong, Taotao; Zhao, Linjing; Feng, Bo; Hu, Xiaofang; Xu, Lisa X; Zhao, Aihua; Zhang, Menghui; Cai, Guoxiang; Cai, Sanjun; Zhou, Zhanxiang; Zheng, Minhua; Zhang, Yan; Jia, Wei

    2013-06-07

    Recent studies suggest that biofluid-based metabonomics may identify metabolite markers promising for colorectal cancer (CRC) diagnosis. We report here a follow-up replication study, after a previous CRC metabonomics study, aiming to identify a distinct serum metabolic signature of CRC with diagnostic potential. Serum metabolites from newly diagnosed CRC patients (N = 101) and healthy subjects (N = 102) were profiled using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). Differential metabolites were identified with statistical tests of orthogonal partial least-squares-discriminant analysis (VIP > 1) and the Mann-Whitney U test (p partial least-squares-discriminant analysis (OPLS-DA) in a learning sample set of 62 CRC patients and 62 matched healthy controls. This established model was able to correctly assign the rest of the samples to the CRC or control groups in a validation set of 39 CRC patients and 40 healthy controls. Consistent with our findings from the previous study, we observed a distinct metabolic signature in CRC patients including tricarboxylic acid (TCA) cycle, urea cycle, glutamine, fatty acids, and gut flora metabolism. Our results demonstrated that a panel of serum metabolite markers is of great potential as a noninvasive diagnostic method for the detection of CRC.

  19. Uptake of Seeds Secondary Metabolites by Virola surinamensis Seedlings

    Directory of Open Access Journals (Sweden)

    Massuo Jorge Kato

    2012-01-01

    Full Text Available The major secondary metabolites and fatty acids occurring in the seeds of Virola surinamensis were monitored by GC-MS during germination and seedling development. The role as carbon source for seedling development was indicated considering that both classes of compounds were similarly consumed in the seeds and that no selective consumption of compounds could be detected.

  20. Bioactive Secondary Metabolites from the Marine Sponge Genus Agelas

    OpenAIRE

    Zhang, Huawei; Dong, Menglian; Chen, Jianwei; Wang, Hong; Tenney, Karen; Crews, Phillip

    2017-01-01

    The marine sponge genus Agelas comprises a rich reservoir of species and natural products with diverse chemical structures and biological properties with potential application in new drug development. This review for the first time summarized secondary metabolites from Agelas sponges discovered in the past 47 years together with their bioactive effects.

  1. Secondary Metabolites from the Marine Sponge Genus Phyllospongia

    OpenAIRE

    Zhang, Huawei; Dong, Menglian; Wang, Hong; Crews, Phillip

    2017-01-01

    Phyllospongia, one of the most common marine sponges in tropical and subtropical oceans, has been shown to be a prolific producer of natural products with a broad spectrum of biological activities. This review for the first time provides a comprehensive overview of secondary metabolites produced by Phyllospongia spp. over the 37 years from 1980 to 2016.

  2. Secondary Metabolites from the Marine Sponge Genus Phyllospongia.

    Science.gov (United States)

    Zhang, Huawei; Dong, Menglian; Wang, Hong; Crews, Phillip

    2017-01-06

    Phyllospongia , one of the most common marine sponges in tropical and subtropical oceans, has been shown to be a prolific producer of natural products with a broad spectrum of biological activities. This review for the first time provides a comprehensive overview of secondary metabolites produced by Phyllospongia spp. over the 37 years from 1980 to 2016.

  3. In vitro evaluation of aliphatic fatty alcohol metabolites of ...

    African Journals Online (AJOL)

    Prof. Ogunji

    In vitro evaluation of aliphatic fatty alcohol metabolites of. Perseaamericana seed as potential antimalarial and antimicrobial agents. Falodun, A.1, 3*, Erharuyi, O.1, 2, Imieje V., 1, 2, Ahomafor, J.1, Akunyuli, C.1,. Jacobs, M.3, Khan, S.3, Hamann, M. T.3, Langer, P.2. 1Department of Pharmaceutical Chemistry, Faculty of ...

  4. An evaluation of the use of blood metabolite concentrations as ...

    African Journals Online (AJOL)

    The aim of this study was to determine whether blood metabolite concentrations in free-ranging indigenous goats are sensitive to expected variations in nutrient supply, and whether they could be used to evaluate different kidding seasons at two locations subject to similar seasonal variations in terms of nutrient supply.

  5. Role of secondary metabolites/antioxidants in vitro

    Science.gov (United States)

    In literature, secondary metabolites are described as natural products, waste, phytopharmaceuticals, bioactive constituents or by-products of the primary metabolism. They occur in many plant genera and microorganisms in vivo and in vitro, and have complex chemical structures specific to the plants w...

  6. Concentration of fecal corticosterone metabolites in dominant versus ...

    African Journals Online (AJOL)

    The objective of this work was to evaluate the concentration of fecal metabolites of corticosterone and to verify if there are differences between dominant and subordinate heifers. The feces of 18 buffalo heifers were collected in the estrous period, to quantify the corticosterone concentrations. The heifers were separated into ...

  7. Impact of secondary metabolites and related enzymes in flax ...

    African Journals Online (AJOL)

    Changes in various physiological defenses including secondary metabolites, proline, total soluble protein and antioxidant enzymes were investigated in leaves and stems of 18 flax lines either resistant or susceptible to powdery mildew. The results showed that the total alkaloids content in flax stems was significantly ...

  8. Volatile metabolites profiling of a Chinese mangrove endophytic ...

    African Journals Online (AJOL)

    Pestalotiopsis JCM2A4, an endophytic fungus originally isolated from leaves of the Chinese mangrove plant Rhizophora mucronata, produces a mixture of volatile metabolites. As determined by gas chromatography and gas chromatography/mass spectrometry (GC/GC-MS), 18 compounds representing all of the hexane ...

  9. Preparation of human drug metabolites using fungal peroxygenases

    Science.gov (United States)

    Marzena Poraj-Kobielska; Matthias Kinne; René Ullrich; Katrin Scheibner; Gernot Kayser; Kenneth E. Hammel; Martin Hofrichter

    2011-01-01

    The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus...

  10. Characterization of primary and secondary metabolites of leaf and ...

    African Journals Online (AJOL)

    This study evaluates the primary and secondary metabolite profiles of Eurycoma longifolia Jack (EL) stems and leaves to determine whether it can be utilized for therapeutic purposes as the roots. A total of six types of extracts were tested. The extracts showed high content of glycosaponins, polysaccharides, proteins and ...

  11. Towards automated identification of metabolites using mass spectral trees

    NARCIS (Netherlands)

    Rojas-Chertó, Miquel

    2014-01-01

    The detailed description of the chemical compounds present in organisms, organs/tissues, biofluids and cells is the key to understand the complexity of biological systems. The small molecules (metabolites) are known to be very diverse in structure and function. However, the identification of the

  12. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    Tinospora crispa Beumee, a herbaceous climber, has been widely used in traditional medicine for treating various ailments such as contusion, septicaemia, fever, fracture, scabies and other tropical ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes have been ...

  13. Penicillium digitatum metabolites on synthetic media and citrus fruits

    DEFF Research Database (Denmark)

    Ariza, M.R.; Larsen, Thomas Ostenfeld; Petersen, Bent O.

    2002-01-01

    Penicillium digitatum has been cultured on citrus fruits and yeast extract sucrose agar media (YES).Cultivation of fungal cultures on solid medium allowed the isolation of two novel tryptoquivaline-like metabolites, tryptoquialanine A (1) and tryptoquialanine B (2), also biosynthesized on citrus...

  14. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.

    NARCIS (Netherlands)

    Vegt, B.J. van der; Lieuwes, N.G.; Cremers, T.I.; Boer, S.F. de; Koolhaas, J.M.

    2003-01-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has

  15. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats

    NARCIS (Netherlands)

    Vegt, Bea J. van der; Lieuwes, Natasja; Cremers, Thomas I.F.H.; Boer, Sietse F. de; Koolhaas, J.M.

    2003-01-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has

  16. Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes

    NARCIS (Netherlands)

    Taguchi, K.; Saitoh, M.; Sato, S.; Asano, M.; Michel, M. C.

    1997-01-01

    We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin

  17. Filling and mining the reactive metabolite target protein database.

    Science.gov (United States)

    Hanzlik, Robert P; Fang, Jianwen; Koen, Yakov M

    2009-04-15

    The post-translational modification of proteins is a well-known endogenous mechanism for regulating protein function and activity. Cellular proteins are also susceptible to post-translational modification by xenobiotic agents that possess, or whose metabolites possess, significant electrophilic character. Such non-physiological modifications to endogenous proteins are sometimes benign, but in other cases they are strongly associated with, and are presumed to cause, lethal cytotoxic consequences via necrosis and/or apoptosis. The Reactive Metabolite Target Protein Database (TPDB) is a searchable, freely web-accessible (http://tpdb.medchem.ku.edu:8080/protein_database/) resource that attempts to provide a comprehensive, up-to-date listing of known reactive metabolite target proteins. In this report we characterize the TPDB by reviewing briefly how the information it contains came to be known. We also compare its information to that provided by other types of "-omics" studies relevant to toxicology, and we illustrate how bioinformatic analysis of target proteins may help to elucidate mechanisms of cytotoxic responses to reactive metabolites.

  18. Prediction of metabolites of epoxidation reaction in MetaTox.

    Science.gov (United States)

    Rudik, A V; Dmitriev, A V; Bezhentsev, V M; Lagunin, A A; Filimonov, D A; Poroikov, V V

    2017-10-01

    Biotransformation is a process of the chemical modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicology studies. Epoxides are formed by some oxidation reactions, usually catalysed by cytochromes P450, and represent a large class of three-membered cyclic ethers. Identification of molecules, which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE - site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 molecules and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labelled Multilevel Neighbourhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service ( http://www.way2drug.com/mg ).

  19. Effects of Fusarium verticilloides , its metabolites and neem leaf ...

    African Journals Online (AJOL)

    41.18%), Fusarium spp. (29.41%) and Rhizopus spp. (23.53%). F. verticilloides metabolite was extracted using dichloromethane and phosphoric acid (10:1) while powdered neem leaf was extracted with ethanol for 72 h. The experiment, which ...

  20. Secondary metabolites of oil palm isolates of Ganoderma zonatum ...

    African Journals Online (AJOL)

    Secondary metabolites of oil palm isolates of Ganoderma zonatum Murill. from Cameroon and their cytotoxicity against five human tumour cell lines. ... Their structures were elucidated by nuclear magnetic resonance (NMR), electron impact ionization mass spectrum experiments (EI-MS) and by comparing with the data ...

  1. Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status

    Directory of Open Access Journals (Sweden)

    Bénédicte Allam-Ndoul

    2016-05-01

    Full Text Available Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW and overweight/obese (Ov/Ob individuals, with or without metabolic syndrome (MetS. Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

  2. Extensive alterations of blood metabolites in pediatric cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Sanchit Gupta

    Full Text Available Cerebral malaria (CM presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy. A paired metabolomics analysis was performed on the plasma samples of Malawian children (n = 11 during CM and at convalescence thirty days later, to identify differentially abundant molecules associated with CM. We also report plasma molecules associated with CM mortality (n = 4 compared to survival (n = 19. Plasma metabolites were identified through ultra high performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry to maximize compound detection and accuracy and then compared to a library for identification. We detected a total of 432 small molecules in the plasma and 247 metabolites were significantly differentially abundant between CM and convalescence (p 1.2. These results highlight the broad changes in blood chemistry during CM. We have identified metabolites that may impact central nervous system physiology and disease outcomes and can be further explored for their mechanistic roles into the pathophysiology of CM.

  3. Larvicidal activity of extracellular secondary metabolites from a ...

    African Journals Online (AJOL)

    The main objective of this investigation was to find mosquito larvicidal secondary metabolites from a basidiomycete – Stereum species (JO5289) – against Aedes aegypti. The Stereum species (JO5289) was collected in July 2005 from undisturbed habitat in Londiani forest in Rift Valley province, Kenya. Extracellular crude ...

  4. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    Science.gov (United States)

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-10-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

  5. Metabolites of antroquinonol found in rat urine following oral administration.

    Science.gov (United States)

    Chen, Chien-Kuang; Kang, Jaw-Jou; Wen, Wu-Che; Chiang, Hui-Fen; Lee, Shoei-Sheng

    2014-04-25

    Four metabolites (1-4) of antroquinonol from rat urine, collected within 24 h after oral administration of antroquinonol, were characterized by HPLC-SPE-NMR. Compounds 1-4 were further isolated by semipreparative HPLC for structure confirmation. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic analyses and HRESIMS data.

  6. Natural occurrence of fungi and fungal metabolites in moldy tomatoes

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    Fresh tomatoes, homegrown and from supermarkets, with developing fungal lesions were collected. Each lesion was sampled, and the resulting fungal cultures were identified morphologically, and extracted for analyzes of secondary metabolites. The tomatoes were incubated at 25 degreesC for a week. e...

  7. Blood metabolites of intensively reared gravid west African dwarf ...

    African Journals Online (AJOL)

    Blood metabolites of intensively reared gravid west African dwarf goats fed pulverized biofibre wastes based diets. ... packed cell volume (PCV), haemoglobin (Hb), mean cell volume (MCV) and mean cell haemoglobin (MCH), while goats on PMC/CsP/BG had significantly increased (p<0.05) white blood cell (WBC).

  8. Biotransformation of cannabidiol in mice. Identification of new acid metabolites.

    Science.gov (United States)

    Martin, B R; Harvey, D J; Paton, W D

    1977-01-01

    The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid.

  9. A Novel Fungal Metabolite with Beneficial Properties for Agricultural Applications

    Directory of Open Access Journals (Sweden)

    Francesco Vinale

    2014-07-01

    Full Text Available Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA, a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction.

  10. Molecular thermodynamics of metabolism: quantum thermochemical calculations for key metabolites.

    Science.gov (United States)

    Hadadi, N; Ataman, M; Hatzimanikatis, V; Panayiotou, C

    2015-04-28

    The present work is the first of a series of papers aiming at a coherent and unified development of the thermodynamics of metabolism and the rationalization of feasibility analysis of metabolic pathways. The focus in this part is on high-level quantum chemical calculations of the thermochemical quantities of relatively heavy metabolites such as amino acids/oligopeptides, nucleosides, saccharides and their derivatives in the ideal gas state. The results of this study will be combined with the corresponding hydration/solvation results in subsequent parts of this work in order to derive the desired thermochemical quantities in aqueous solutions. The above metabolites exist in a vast conformational/isomerization space including rotational conformers, tautomers or anomers exhibiting often multiple or cooperative intramolecular hydrogen bonding. We examine the challenges posed by these features for the reliable estimation of thermochemical quantities. We discuss conformer search, conformer distribution and averaging processes. We further consider neutral metabolites as well as protonated and deprotonated metabolites. In addition to the traditional presentation of gas-phase acidities, basicities and proton affinities, we also examine heats and free energies of ionic species. We obtain simple linear relations between the thermochemical quantities of ions and the formation quantities of their neutral counterparts. Furthermore, we compare our calculations with reliable experimental measurements and predictive calculations from the literature, when available. Finally, we discuss the next steps and perspectives for this work.

  11. Effects of Fusarium verticilloides, its metabolites and neem leaf ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-18

    Jul 18, 2008 ... Maize (Zea mays L.) seed samples were collected from three markets in Minna, Niger State to investigate the effect of Fusarium verticilloides, its metabolites and neem (Azadirachta indica) leaf ethanolic extract on germination of the seeds and seedling vigour. Among the fungi genera isolated from the ...

  12. Functional nucleic acids as in vivo metabolite and ion biosensors.

    Science.gov (United States)

    Alsaafin, Alaa; McKeague, Maureen

    2017-08-15

    Characterizing the role of metabolites, metals, and proteins is required to understand normal cell function, and ultimately, elucidate the mechanism of disease. Metabolite concentration and transformation results collected from cell lysates or fixed-cells conceal important dynamic information and differences between individual cells that often have profound functional consequences. Functional nucleic acid-based biosensors are emerging tools that are capable of monitoring ions and metabolites in cell populations or whole animals. Functional nucleic acids (FNAs) are a class of biomolecules that can exhibit either ligand binding or enzymatic activity. Unlike their protein analogues or the use of instrument-based analysis, FNA-based biosensors are capable of entering cells without disruption to the cellular environment and can report on the concentration, dynamics, and spatial localization of molecules in cells. Here, we review the types of FNAs that have been used as in vivo biosensors, and how FNAs can be coupled to transduction systems and delivered inside cells. We also provide examples from the literature that demonstrate their impact in practical applications. Finally, we comment on the critical limitations that need to be addressed to enable their use for single-cell dynamic tracking of metabolites and ions in vivo. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  13. Blood metabolites and their relatioriship to dairy cattle productive ...

    African Journals Online (AJOL)

    Sixty-four dairy cows (B taums x B indicus crosses) belonging to 40 peri-urban smallholder farms were investigated for relationship of their blood metabolites, body condition score (BCS) and body weight to milk yield and reproductive performance. Feed availability and quality were monitored monthly. Plasma ...

  14. Metabolite Profiles of Male and Female Humboldt Penguins

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Levengood

    2015-10-01

    Full Text Available We examined 185 metabolites in 30 adult Humboldt Penguins (Spheniscus humboldti nesting at the Punta San Juan Marine Protected Area, Peru, in order to examine gender differences in metabolome profiles, particularly those involved in metabolism and energetics. The majority of the compounds identified were fatty (26% of total identified compounds, organic (19%, and amino (16% acids. We were able to differentiate male and female penguins with 96.6% accuracy on the basis of 12 metabolites, most of which are involved in lipid and carbohydrate metabolism. These included 2-oxoglutarate, erythronic acid, GABA, mannitol, sedoheptulose 7-phosphate, and serine and six metabolites present in higher concentrations in females compared to males (2-aminoadipic acid, O-phosphorylethanolamine, glycerol 2-phosphate, glycerol 3-phosphate, pantothenic acid, and creatinine. Of these, 2-oxoglutarate and glycerol 3-phosphate were key metabolites distinguishing gender. Our results indicated that male and female Humboldt Penguins were characterized by differing metabolic states. Such differences could be important to individual and brood survival in times of environmental stress.

  15. Metabolite modifications in Solanum lycopersicum roots and leaves ...

    African Journals Online (AJOL)

    During the treatment, Cd accumulated significantly in the roots compared to stems and leaves. Plant growth (root, stem and leaf) decreased when Cd concentration increased. The analysis of 1H-NMR spectra of polar extracts showed clear differences between metabolites amounts (soluble sugars, organic and amino acids) ...

  16. Blood lipid metabolites and meat lipid peroxidation responses of ...

    African Journals Online (AJOL)

    Blood samples were collected from broilers to evaluate serum biochemical metabolites on day 41. Thigh meat samples were provided and analysed after 1, 5 and 10 days' storage to evaluate lipid peroxidation at the end of the experiment. Fat and protein contents of thigh muscle and abdominal fat weight were measured ...

  17. Role of secondary metabolites biosynthesis in resistance to cotton ...

    African Journals Online (AJOL)

    Secondary metabolites production in healthy and diseased sample of leaves of cotton varieties after the attack of CLCuV found maximum phenolics, carotenoids, chlorophyll a, chlorophyll b and total chlorophyll a and b in healthy sample and minimum contents present in diseased sample. CIM-446 was the best variety to ...

  18. Bioactive metabolite production by Streptomyces albolongus in favourable environment

    Directory of Open Access Journals (Sweden)

    Myn Uddin

    2013-06-01

    Full Text Available Objectives: Demand for new antibiotic is rising up due to continuous resistance risk against conventional antibiotic.This attempt was taken to find out a novel antimicrobial metabolite.Methods: Chili field antagonistic actinomycetes Streptomyces albolongus was isolated and tested for optimum antimicrobialmetabolite production. Primary screening was done by selective media and antibiotic assay was done by agarcup plate method. Fermented product was recovered by separating funnel using suitable solvent.Results: Maximum antimicrobial metabolite production was found at temperature 35°C and pH 9.0 and on 6th day ofincubation. The medium consisting of corn steep liquor (0.2%, glucose (1.0%, NaCl (0.5%, K2HPO4 (0.1% was screenedout as suitable medium for maximum antimicrobial production. Sucrose was found as the best carbon source amongfour sources. The antimicrobial metabolite was found to be stable at pH and temperature up to 11.0 and 100°C respectively.The active agent was best extracted with chloroform. The antimicrobial spectrum of the metabolite was wideand shows activity against Shigella dysenteriae (AE14612, Shigella sonnei (CRL, ICDDR, B, Salmonella typhi (AE14296,Vibrio cholerae (AE14748, Pseudomonas aeruginosa (CRL, ICDDR, B, Bacillus cereus (BTCC19, Staphylococcus aureus(ATCC6538, Bacillus subtilis (BTTC17 and Bacillus megaterium (BTTC18.Conclusions: The findings of antibacterial activity of S. albolongus against several species of human pathogens includingboth Gram-positive and Gram-negative bacteria indicated that our produced material might be an alternative antimicrobialsubstance to control human diseases. J Microbiol Infect Dis 2013; 3(2: 75-82Key words: Streptomyces albolongus, antimicrobial metabolite, optimum production, antimicrobial spectrum

  19. Profiling and Distribution of Metabolites of Procyanidin B2 in Mice by UPLC-DAD-ESI-IT-TOF-MSn Technique

    Directory of Open Access Journals (Sweden)

    Ying Xiao

    2017-05-01

    Full Text Available The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MSn without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (−-epicatechin by scission of the flavanol interflavanic bond C4–C8, including 16 aromatic metabolites, 5 conjugated metabolites, 3 ring-cleavage metabolites, and 2 phenylvalerolactone metabolites. Additionally, 14 metabolites were conjugates of free procyanidin B2, comprising 9 methylation metabolites, 8 sulfation metabolites, 5 hydration metabolites, 2 hydroxylation metabolites, 1 hydrogenation metabolites, and 1 glucuronidation metabolites. The results of metabolite distributions in organs indicated that the conjugated reaction of free procyanidin B2 mainly occurred in liver and diversified metabolites forms were observed in small intestine. The metabolic components of procyanidin B2 identified in mice provided useful information for further study of the bioactivity and mechanism of its action.

  20. Quantification of a bacterial secondary metabolite by SERS combined with SLM extraction for bioprocess monitoring.

    Science.gov (United States)

    Morelli, Lidia; Andreasen, Sune Zoëga; Jendresen, Christian Bille; Nielsen, Alex Toftgaard; Emnéus, Jenny; Zór, Kinga; Boisen, Anja

    2017-11-20

    During the last few decades, great advances have been reached in high-throughput design and building of genetically engineered microbial strains, leading to a need for fast and reliable screening methods. We developed and optimized a microfluidic supported liquid membrane (SLM) extraction device and combined it with surface enhanced Raman scattering (SERS) sensing for the screening of a biological process, namely for the quantification of a bacterial secondary metabolite, p-coumaric acid (pHCA), produced by Escherichia coli. The microfluidic device proved to be robust and reusable, enabling efficient removal of interfering compounds from the real samples, reaching more than 13-fold up-concentration of the donor at 10 μL min -1 flow rate. With this method, we quantified pHCA directly from the bacterial supernatant, distinguishing between various culture conditions based on the pHCA production yield. The obtained data showed good correlation with HPLC analysis.

  1. Cyclophosphamide metabolite inducing apoptosis in RLS mouse lymphosarcoma cells is a substrate for P-glycoprotein.

    Science.gov (United States)

    Patutina, O A; Mironova, N L; Logashenko, E B; Popova, N A; Nikolin, V P; Vasil'ev, G V; Kaledin, V I; Zenkova, M A; Vlasov, V V

    2012-01-01

    RLS lymphosarcoma characterized by enhanced expression of mdr1a and mdr1b genes encoding P-glycoprotein is insensitive to low doses of cyclophosphamide, but is susceptible to its high doses approximating the maximum tolerated doses. Induction of apoptotic death of RLS cells by high doses of cyclophosphamide was demonstrated by cytofluorometry and electrophoresis. Experiments on RLS(40) tumor cells derived from RLS lymphosarcoma and characterized by more intensive expression of mdr1a/1b genes showed that the therapeutic effects of cyclophosphamide increased under conditions of simultaneous suppression of these genes by specific small interfering RNA (siRNA). These findings suggest that active cyclophosphamide metabolite can be a substrate for P-glycoprotein.

  2. Phytohormones and Effects on Growth and Metabolites of Microalgae: A Review

    Directory of Open Access Journals (Sweden)

    Xingfeng Han

    2018-04-01

    Full Text Available Microalgae cultivation is booming in agriculture, aquaculture, and bioenergy sectors. A wide range of bioactive compounds with attractive properties can be produced with microalgae, including pigments, vitamins, proteins, carbohydrates, and lipids. The biofuel yields from microalgae can exceed the yields obtained with energy crops by 10–100 times. Therefore, such cultivation is promising for the regulation of the biosynthesis of microalagae with phytohormones, which can enhance the production of high-valued bioproducts. This review reports the effect of auxins, abscisic acid, cytokinins, gibberellins, and ethylene on microalgal growth and metabolites, as well as the crosstalk of different phytohormones. The use of phytohormones is also promising because it can also reduce the inputs necessary to grow the selected microalgae and maximize the yields.

  3. Physiological performance, secondary metabolite and expression profiling of genes associated with drought tolerance in Withania somnifera.

    Science.gov (United States)

    Sanchita; Singh, Ruchi; Mishra, Anand; Dhawan, Sunita S; Shirke, Pramod A; Gupta, Madan M; Sharma, Ashok

    2015-11-01

    Physiological, biochemical, and gene expression responses under drought stress were studied in Withania somnifera. Photosynthesis rate, stomatal conductance, transpiration rate, relative water content, chlorophyll content, and quantum yield of photosystems I and II (PSI and PSII) decreased in response to drought stress. Comparative expression of genes involved in osmoregulation, detoxification, signal transduction, metabolism, and transcription factor was analyzed through quantitative RT-PCR. The genes encoding 1-pyrroline-5-carboxylate synthetase (P5CS), glutathione S-transferase (GST), superoxide dismutase (SOD), serine threonine-protein kinase (STK), serine threonine protein phosphatase (PSP), aldehyde dehydrogenase (AD), leucoanthocyanidin dioxygenase/anthocyanin synthase (LD/AS), HSP, MYB, and WRKY have shown upregulation in response to drought stress condition in leaf tissues. Enhanced detoxification and osmoregulation along with increased withanolides production were also observed under drought stress. The results of this study will be helpful in developing stress-tolerant and high secondary metabolite yielding genotypes.

  4. Secondary metabolite profiling of Alternaria dauci, A. porri, A. solani, and A. tomatophila

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Dongo, Anita; Pryor, Barry M.

    2008-01-01

    Chemotaxonomy (secondary metabolite profiling) has been shown to be of great value in the classification and differentiation in Ascomycota. However, few studies have investigated the use of metabolite production for classification and identification purposes of plant pathogenic Alternaria species...

  5. Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs

    NARCIS (Netherlands)

    Gül, Turan; Bischoff, Rainer; Permentier, Hjalmar

    2015-01-01

    Identification of potentially toxic metabolites is important for drug discovery and development. Synthesis of drug metabolites is typically performed by organic synthesis or enzymatic methods, but is not always straightforward. Electrochemical (EC) methods are increasingly used to study drug

  6. Assessing the accuracy of software predictions of mammalian and microbial metabolites

    Science.gov (United States)

    New chemical development and hazard assessments benefit from accurate predictions of mammalian and microbial metabolites. Fourteen biotransformation libraries encoded in eight software packages that predict metabolite structures were assessed for their sensitivity (proportion of ...

  7. Microsomal metabolism of trenbolone acetate metabolites: Transformation product formation and bioactivity.

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbo...

  8. Polar metabolites of polycyclic aromatic compounds from fungi are potential soil and groundwater contaminants

    DEFF Research Database (Denmark)

    Boll, Esther Sørensen; Johnsen, Anders R.; Christensen, Jan H.

    2015-01-01

    and either hydroxylated or oxidized to carboxylic acids at the methyl group. The metabolism of the sulfur-containing heterocyclic PAC resulted in sulfate conjugates. The sorption of the PAC metabolites to three soils was determined using a batch equilibrium method, and partition coefficients (Kd's) were......-methylphenanthrene, 1-methylpyrene), and one sulfur-containing heterocyclic PAC (dibenzothiophene). Fifty-eight metabolites were tentatively identified; metabolites from the un-substituted PACs were hydroxylated and sulfate conjugated, whereas metabolites from alkyl-substituted PACs were sulfate conjugated...... calculated for fourteen representative metabolites. Sulfate conjugated metabolites displayed Kd's below 70 whereas the metabolites with both a sulfate and a carboxylic acid group had Kd's below 2.8. The low Kd's of water-soluble PAC metabolites indicate high mobility in soil and a potential for leaching...

  9. Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium alborcoremium: chemotaxonomic significance and pathological implications

    DEFF Research Database (Denmark)

    Overy, David Patrick; Larsen, Thomas Ostenfeld; Dalsgaard, P.W.

    2005-01-01

    A survey of Penicillium albocoremium was undertaken to identify potential taxonomic metabolite markers. One major and four minor metabolites were consistently produced by the 19 strains surveyed on three different media. Following purification and spectral studies, the metabolites were identified...

  10. Preliminary study to prepare a reference material of toluene metabolite - o-cresol and benzene metabolite-phenol - in human

    Czech Academy of Sciences Publication Activity Database

    Šperlingová, I.; Dabrowská, L.; Stránský, V.; Kučera, Jan; Tichý, M.

    2006-01-01

    Roč. 11, č. 5 (2006), s. 231-235 ISSN 0949-1775 R&D Projects: GA MZd NR7831 Institutional research plan: CEZ:AV0Z10480505 Keywords : reference material * toluene metabolites * o-cresol Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.640, year: 2006

  11. Metabolite diversity in the plant pathogen Alternaria brassicicola: factors affecting production of brassicicolin A, depudecin, phomapyrone A and other metabolites.

    Science.gov (United States)

    Pedras, M Soledade C; Park, Myung Ryeol

    2015-01-01

    A systematic investigation of the metabolites of Alternaria brassicicola produced under various culture conditions is reported. The phytotoxin brassicicolin A is produced in significantly larger amounts in potato dextrose broth than in minimal medium cultures. In general an increase in the incubation temperature of cultures 23-30 C increases the production of brassicicolin A but decreases depudecin production. Reducing or eliminating nitrate from culture media or adding ammonium chloride increases the production of brassicicolin A at 30 C, depudecin at 23 C and α-acetylorcinol at either temperature, suggesting that nitrogen represses their biosynthesis. Siderophores are detected in cultures of A. brassicicola containing low and high ferric ion concentrations. The metabolites α-acetylorcinol and tyrosol are isolated for the first time from cultures of A. brassicicola, and α-acetylorcinol is synthesized in four steps and 36% overall yield. Only brassicicolin A and no other isolated metabolites, including depudecin and phomapyrone A, display phytotoxicity on leaves of Brassica species (up to 5.0 mM). Epigenetic modifiers, 5-azacitidin (5-AZA), suberoylanilide hydroxamic acid (SAHA) and suberoyl bis-hydroxamic acid (SBHA) do not affect the metabolite profiles of liquid cultures of this fungal pathogen. © 2015 by The Mycological Society of America.

  12. Metabolomics and bioanalysis of terpenoid derived secondary metabolites : Analysis of Cannabis sativa L. metabolite production and prenylases for cannabinoid production

    NARCIS (Netherlands)

    Muntendam, Remco

    2015-01-01

    Cannabinoid research has gained a renenewed interest by both the public and scientist. Focus is mainly directed to the medicinal activities, as reported for various cannabinoid structures. This thesis focusses on prenyl-derived secondary metabolites with main focus on cannabinoids. Firstly the

  13. Concentration of metabolites from low-density planktonic communities for environmental metabolomics using nuclear magnetic resonance spectroscopy.

    Science.gov (United States)

    Everroad, R Craig; Yoshida, Seiji; Tsuboi, Yuuri; Date, Yasuhiro; Kikuchi, Jun; Moriya, Shigeharu

    2012-04-07

    Environmental metabolomics is an emerging field that is promoting new understanding in how organisms respond to and interact with the environment and each other at the biochemical level. Nuclear magnetic resonance (NMR) spectroscopy is one of several technologies, including gas chromatography-mass spectrometry (GC-MS), with considerable promise for such studies. Advantages of NMR are that it is suitable for untargeted analyses, provides structural information and spectra can be queried in quantitative and statistical manners against recently available databases of individual metabolite spectra. In addition, NMR spectral data can be combined with data from other omics levels (e.g. transcriptomics, genomics) to provide a more comprehensive understanding of the physiological responses of taxa to each other and the environment. However, NMR is less sensitive than other metabolomic techniques, making it difficult to apply to natural microbial systems where sample populations can be low-density and metabolite concentrations low compared to metabolites from well-defined and readily extractable sources such as whole tissues, biofluids or cell-cultures. Consequently, the few direct environmental metabolomic studies of microbes performed to date have been limited to culture-based or easily defined high-density ecosystems such as host-symbiont systems, constructed co-cultures or manipulations of the gut environment where stable isotope labeling can be additionally used to enhance NMR signals. Methods that facilitate the concentration and collection of environmental metabolites at concentrations suitable for NMR are lacking. Since recent attention has been given to the environmental metabolomics of organisms within the aquatic environment, where much of the energy and material flow is mediated by the planktonic community, we have developed a method for the concentration and extraction of whole-community metabolites from planktonic microbial systems by filtration. Commercially

  14. Effects of Lactobacillus Johnsonii AJ5 Metabolites on Nutrition, Nosema Ceranae Development and Performance of Apis Mellifera L.

    Directory of Open Access Journals (Sweden)

    Piano Fiorella G. De

    2017-06-01

    Full Text Available The European honey bee (Apis mellifera L. is known to be affected by such stress factors as pathogen load, poor nutrition and depressed immunity. Nosema ceranae is one of the main parasites that affect colony populations. The relationship between the stress factors and honey bee-bacteria symbiosis appears as an alternative to enhance bee health. The aim of this study was to evaluate the effect of the oral administration of bacterial metabolites produced by Lactobacillus johnsonii AJ5 on nutritional parameters, the N. ceranae development and the performance of A. mellifera colonies. Laboratory assays were performed and demonstrated that the bacterial metabolites did not have a toxic effect on bees. Field trial showed an increase of colonies population over time. Also, a decreasing trend of fat bodies per bee was detected in all colonies but there were no evident changes on abdomen protein content at the end of the assay. Lastly, N. ceranae prevalence showed a tendency to reduce with the organic acids. Future studies should be performed to increase our knowledge of the physiological effects of bacterial metabolites on the health of bee colonies.

  15. Metabolite profiling reveals novel multi-level cold responses in the diploid model Fragaria vesca (woodland strawberry).

    Science.gov (United States)

    Rohloff, Jens; Kopka, Joachim; Erban, Alexander; Winge, Per; Wilson, Robert C; Bones, Atle M; Davik, Jahn; Randall, Stephen K; Alsheikh, Muath K

    2012-05-01

    Winter freezing damage is a crucial factor in overwintering crops such as the octoploid strawberry (Fragaria × ananassa Duch.) when grown in a perennial cultivation system. Our study aimed at assessing metabolic processes and regulatory mechanisms in the close-related diploid model woodland strawberry (Fragaria vescaL.) during a 10-days cold acclimation experiment. Based on gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) metabolite profiling of three F. vesca genotypes, clear distinctions could be made between leaves and non-photosynthesizing roots, underscoring the evolvement of organ-dependent cold acclimation strategies. Carbohydrate and amino acid metabolism, photosynthetic acclimation, and antioxidant and detoxification systems (ascorbate pathway) were strongly affected. Metabolic changes in F. vesca included the strong modulation of central metabolism, and induction of osmotically-active sugars (fructose, glucose), amino acids (aspartic acid), and amines (putrescine). In contrast, a distinct impact on the amino acid proline, known to be cold-induced in other plant systems, was conspicuously absent. Levels of galactinol and raffinose, key metabolites of the cold-inducible raffinose pathway, were drastically enhanced in both leaves and roots throughout the cold acclimation period of 10 days. Furthermore, initial freezing tests and multifaceted GC/TOF-MS data processing (Venn diagrams, independent component analysis, hierarchical clustering) showed that changes in metabolite pools of cold-acclimated F. vesca were clearly influenced by genotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Metabolite diversification by cultivation of the endophytic fungus Dothideomycete sp. in halogen containing media: Cultivation of terrestrial fungus in seawater.

    Science.gov (United States)

    Wijesekera, Kanchana; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2017-06-01

    The endophytic fungus, Dothideomycete sp. CRI7, isolated from the terrestrial plant, Tiliacora triandra, was salt tolerant, capable of growing in the culture medium prepared from seawater; salts in seawater did not have any effects on the fungal growth. Metabolite productions of the fungus CRI7 cultivated in media prepared from seawater (MSW), prepared from deionized water supplemented with potassium bromide (MKBr) or potassium iodide (MKI), and prepared from deionized water (MDW) were investigated. It was found that the cultivation of the fungus CRI7 in MKBr and MSW enabled the fungus to produce nine new metabolites (1-9). The production of an azaphilone, austdiol (10), of the fungus CRI7 grown in MDW was 0.04g/L, which was much lower than that grown in MSW, MKBr, and MKI media which provided the yields of 0.5, 0.9, and 1.2g/L, respectively, indicating that halogen salts significantly enhanced the production of the polyketide 10. The cultivation of terrestrial fungi in media containing halogen salts could therefore be useful for the metabolite diversification by one strain-many compounds (OSMAC) approach. Moreover, the isolated polyketides had significant biosynthetic relationship, suggesting that the cultivation of fungi in halogen containing media could provide the insights into certain polyketide biosynthesis. One of the isolated compounds exhibited antibacterial activity with the MIC value of 100μg/mL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Spatial mapping of lichen specialized metabolites using LDI-MSI: chemical ecology issues for Ophioparma ventosa

    OpenAIRE

    Legouin, Béatrice; Geairon, Audrey; Rogniaux, Hélène; Lohezic-Le Devehat, Francoise; Obermayer, Walter

    2016-01-01

    Imaging mass spectrometry techniques have become a powerful strategy to assess the spatial distribution of metabolites in biological systems. Based on auto-ionisability of lichen metabolites using LDI-MS, we herein image the distribution of major secondary metabolites (specialized metabolites) from the lichen Ophioparma ventosa by LDI-MSI (Mass Spectrometry Imaging). Such technologies offer tremendous opportunities to discuss the role of natural products through spatial mapping, their distrib...

  18. Profiling and Distribution of Metabolites of Procyanidin B2 in Mice by UPLC-DAD-ESI-IT-TOF-MSn Technique

    OpenAIRE

    Xiao, Ying; Hu, Zhongzhi; Yin, Zhiting; Zhou, Yiming; Liu, Taiyi; Zhou, Xiaoli; Chang, Dawei

    2017-01-01

    The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MSn without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites) were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (−)-epicatechin by scission of the flavanol interflavanic bond C4–C8,...

  19. Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

    DEFF Research Database (Denmark)

    Autrup, Herman

    1979-01-01

    of glucuronides accounts for only 6 per cent of the water-soluble metabolites. Hydrolysis of the sulfate esters with arylsulfatase and the glucuronides with β-glucuronidase released metabolites of benzo[a]pyrene that were extractable with organic solvent. Separation of these metabolites by high-pressure liquid...

  20. Antibacterial Secondary Metabolites from the Cave Sponge Xestospongia sp.

    Directory of Open Access Journals (Sweden)

    Sridevi Ankisetty

    2012-05-01

    Full Text Available Chemical investigation of the cave sponge Xestospongia sp. resulted in the isolation of three new polyacetylenic long chain compounds along with two known metabolites. The structures of the new metabolites were established by NMR and MS analyses. The antibacterial activity of the new metabolites was also evaluated.

  1. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a... testing of specimens to determine whether they are negative for the indicated drugs and drug metabolites...

  2. NEW METABOLITES OF THE DRUG 5-AMINOSALICYLIC ACID .2. N-FORMYL-5-AMINOSALICYLIC ACID

    DEFF Research Database (Denmark)

    Tjornelund, J.; Hansen, S. H.; Cornett, Claus

    1991-01-01

    1. A new metabolite of the drug 5-aminosalicylic acid (5-ASA) has been found in urine from pigs and in plasma of humans. The metabolite has been isolated from pig urine using an XAD-2 column and purified using preparative h.p.l.c. 2. The metabolite has been identified as N-formyl-5-ASA (5...

  3. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites than...

  4. Metabolite ratios as potential biomarkers for type 2 diabetes : a DIRECT study

    NARCIS (Netherlands)

    Molnos, Sophie; Wahl, Simone; Haid, Mark; Eekhoff, E Marelise W; Pool, René; Floegel, Anna; Deelen, Joris; Much, Daniela; Prehn, Cornelia; Breier, Michaela; Draisma, Harmen H; van Leeuwen, Nienke; Simonis-Bik, Annemarie M C; Jonsson, Anna; Willemsen, Gonneke; Bernigau, Wolfgang; Wang-Sattler, Rui; Suhre, Karsten; Peters, Annette; Thorand, Barbara; Herder, Christian; Rathmann, Wolfgang; Roden, Michael; Gieger, Christian; Kramer, Mark H H; van Heemst, Diana; Pedersen, Helle K; Gudmundsdottir, Valborg; Schulze, Matthias B; Pischon, Tobias; de Geus, Eco J C; Boeing, Heiner; Boomsma, Dorret I; Ziegler, Anette G; Slagboom, P. Eline; Hummel, Sandra; Beekman, Marian; Grallert, Harald; Brunak, Søren; McCarthy, Mark I; Gupta, Ramneek; Pearson, Ewan R; Adamski, Jerzy; 't Hart, Leen M

    2018-01-01

    AIMS/HYPOTHESIS: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and

  5. New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites.

    Science.gov (United States)

    Kato, Masashi; Suzuki, Gen; Ohtake, Hiroto; Seto, Yoshiki; Onoue, Satomi

    2015-11-01

    Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M(-1)cm(-1) (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Baicalin and its metabolites suppresses gluconeogenesis through activation of AMPK or AKT in insulin resistant HepG-2 cells.

    Science.gov (United States)

    Wang, Tao; Jiang, Hongmei; Cao, Shijie; Chen, Qian; Cui, Mingyuan; Wang, Zhijie; Li, Dandan; Zhou, Jing; Wang, Tao; Qiu, Feng; Kang, Ning

    2017-12-01

    Scutellaria baicalensis Georgi (S. baicalensis), as a traditional Chinese herbal medicine, is an important component of several famous Chinese medicinal formulas for treating patients with diabetes mellitus. Baicalin (BG), a main bioactive component of S. baicalensis, has been reported to have antidiabetic effects. However, pharmacokinetic studies have indicated that BG has poor oral bioavailability. Therefore, it is hard to explain the pharmacological effects of BG in vivo. Interestingly, several reports show that BG is extensively metabolized in rats and humans. Therefore, we speculate that the BG metabolites might be responsible for the pharmacological effects. In this study, BG and its three metabolites (M1-M3) were examined their effects on glucose consumption in insulin resistant HepG-2 cells with a commercial glucose assay kit. Real-time PCR and western blot assay were used to confirm genes and proteins of interest, respectively. The results demonstrate that BG and its metabolites (except for M3) enhanced the glucose consumption which might be associated with inhibiting the expression of the key gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2). Further study found that BG and M1 could suppress hepatic gluconeogenesis via activation of the AMPK pathway, while M2 could suppress hepatic gluconeogenesis via activation of the PI3K/AKT signaling pathway. Taken together, our findings suggest that both BG and its metabolites have antihyperglycemic activities, and might be the active forms of oral doses of BG in vivo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Enterobacter aerogenes metabolites enhance Microcystis aeruginosa biomass recovery for sustainable bioflocculant and biohydrogen production.

    Science.gov (United States)

    Xu, Liang; Zhou, Mo; Ju, Hanyu; Zhang, Zhenxing; Zhang, Jiquan; Sun, Caiyun

    2018-04-07

    We report a recycling bioresource involving harvesting of Microcystis aeruginosa using the bioflocculant (MBF-32) produced by Enterobacter aerogenes followed by the recovery of the harvested M. aeruginosa as the main substrate for the sustainable production of MBF-32 and biohydrogen. The experimental results indicate that the efficiency of bioflocculation exceeded 90% under optimal conditions. The harvested M. aeruginosa was further recycled as the main substrate for the supply of necessary elements. The highest yield (3.6±0.1g/L) of MBF-32 could be obtained from 20g/L of wet biomass of M. aeruginosa with an additional 20g/L of glucose as the extra carbon source. The highest yield of biohydrogen was 35mL of H 2 /g (dw) algal biomass, obtained from 20g/L of wet biomass of M. aeruginosa with an additional 10g/L of glycerol. Transcriptome analyses indicated that MBF-32 was mainly composed of polysaccharide and tyrosine/tryptophan proteins. Furthermore, NADH synthase and polysaccharide export-related genes were found to be up-regulated. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Epidermal Microfluidic Electrochemical Detection System: Enhanced Sweat Sampling and Metabolite Detection.

    Science.gov (United States)

    Martín, Aida; Kim, Jayoung; Kurniawan, Jonas F; Sempionatto, Juliane R; Moreto, Jose R; Tang, Guangda; Campbell, Alan S; Shin, Andrew; Lee, Min Yul; Liu, Xiaofeng; Wang, Joseph

    2017-12-22

    Despite tremendous recent efforts, noninvasive sweat monitoring is still far from delivering its early analytical promise. Here, we describe a flexible epidermal microfluidic detection platform fabricated through hybridization of lithographic and screen-printed technologies, for efficient and fast sweat sampling and continuous, real-time electrochemical monitoring of glucose and lactate levels. This soft, skin-mounted device judiciously merges lab-on-a-chip and electrochemical detection technologies, integrated with a miniaturized flexible electronic board for real-time wireless data transmission to a mobile device. Modeling of the device design and sweat flow conditions allowed optimization of the sampling process and the microchannel layout for achieving attractive fluid dynamics and rapid filling of the detection reservoir (within 8 min from starting exercise). The wearable microdevice thus enabled efficient natural sweat pumping to the electrochemical detection chamber containing the enzyme-modified electrode transducers. The fabricated device can be easily mounted on the epidermis without hindrance to the wearer and displays resiliency against continuous mechanical deformation expected from such epidermal wear. Amperometric biosensing of lactate and glucose from the rapidly generated sweat, using the corresponding immobilized oxidase enzymes, was wirelessly monitored during cycling activity of different healthy subjects. This ability to monitor sweat glucose levels introduces new possibilities for effective diabetes management, while similar lactate monitoring paves the way for new wearable fitness applications. The new epidermal microfluidic electrochemical detection strategy represents an attractive alternative to recently reported colorimetric sweat-monitoring methods, and hence holds considerable promise for practical fitness or health monitoring applications.

  9. DETERMINATION OF PRIMARY METABOLITES IN CEREAL MILLING FRACTIONS

    Directory of Open Access Journals (Sweden)

    Eva Ivanišová

    2013-10-01

    Full Text Available The aim of this study was to determine of primary metabolites (content of starch, total dietary fibre, reducing sugars, proteins and amino acids in four milling fractions of selected cereals (barley, wheat, oat, spelt, rye, triticale grew in the year 2009. It was found that flour fractions (break flour and reduction flour showed the lower content of primary metabolites than bran fractions (fine bran and coarse bran. The aim of this study was also to mention the potential use of bran parts of grain - substances from these parts can be isolated and after treatment, which causes their efficiently usable for human body, they can be used for fortification of wide range of food products.

  10. Global metabolite analysis of yeast: evaluation of sample preparation methods

    DEFF Research Database (Denmark)

    Villas-Bôas, Silas Granato; Højer-Pedersen, Jesper; Åkesson, Mats Fredrik

    2005-01-01

    Sample preparation is considered one of the limiting steps in microbial metabolome analysis. Eukaryotes and prokaryotes behave very differently during the several steps of classical sample preparation methods for analysis of metabolites. Even within the eukaryote kingdom there is a vast diversity...... of cell structures that make it imprudent to blindly adopt protocols that were designed for a specific group of microorganisms. We have therefore reviewed and evaluated the whole sample preparation procedures for analysis of yeast metabolites. Our focus has been on the current needs in metabolome analysis...... with reduced pressure solvent evaporation and therefore represents an attractive sample preparation procedure for high-throughput metabolome analysis of yeasts. Copyright (c) 2005 John Wiley & Sons, Ltd....

  11. Quantification of stable isotope label in metabolites via mass spectrometry.

    Science.gov (United States)

    Huege, Jan; Goetze, Jan; Dethloff, Frederik; Junker, Bjoern; Kopka, Joachim

    2014-01-01

    Isotope labelling experiments with stable or radioactive isotopes have long been an integral part of biological and medical research. Labelling experiments led to the discovery of new metabolic pathways and made it possible to calculate the fluxes responsible for a metabolic phenotype, i.e., the qualitative and quantitative composition of metabolites in a biological system. Prerequisite for efficient isotope labelling experiments is a reliable and precise method to analyze the redistribution of isotope label in a metabolic network. Here we describe the use of the CORRECTOR program, which utilizes matrix calculations to correct mass spectral data from stable isotope labelling experiments for the distorting effect of naturally occurring stable isotopes (NOIs). CORRECTOR facilitates and speeds up the routine quantification of experimentally introduced isotope label from multiple mass spectral readouts, which are generated by routine metabolite profiling when combined with stable isotope labelling experiments.

  12. Quantification of benzoxazinoids and their metabolites in Nordic breads

    DEFF Research Database (Denmark)

    Dihm, Katharina; Vendelbo Lind, Mads; Sundén, Henrik

    2017-01-01

    Benzoxazinoids (Bx) and their metabolites are molecules with suggested health effects in humans, found in cereal grains and consequently in cereal foods. However, to date little is known about the amount of Bx in our diet. In this study, deuterated standards 2-hydroxy-1,4-benzoxazin-3-one (HBOA-d4......) and 2-hydroxy-N-(2-hydroxyphenyl) acetamide (HHPAA-d4) were synthesized, to allow quantification of nine Bx and their metabolites in 30 breads and flours from Nordic countries by UHPLC-MS/MS. Samples containing rye had larger amounts of Bx (143–3560 µg/g DM) than the ones containing wheat (11–449 µg...

  13. Characterization of the major metabolite of sampangine in rats.

    Science.gov (United States)

    Orabi, K Y; Walker, L A; Clark, A M; Hufford, C D

    2000-05-01

    Sampangine (1) is a plant-derived antifungal copyrine alkaloid extracted from the stem bark of Cananga odorata. Although it possesses potent in vitro antifungal activity, 1 is devoid of significant and reproducible in vivo activity in a mouse model of cryptococcosis. Speculating that the lack of in vivo activity could be due to metabolism, a study was undertaken to begin to develop an understanding of the pharmacokinetics, and particularly metabolism of 1. Following intraperitoneal administration of 1 to rats, urine was collected, extracted, and chromatographed over a reversed-phase C(18) silica column to yield the major metabolite, SAM MM1 (2), which was identified by NMR and MS to be an O-glucuronide conjugate of sampangine. In addition, two other unstable, structurally uncharacterized minor metabolites were produced, as evidenced by HPLC analysis. Evaluation of the antifungal and antibacterial activities of 2 showed it to have remarkable in vitro activity against Cryptococcus neoformans.

  14. Secondary Metabolites of Mangrove-Associated Strains of Talaromyces

    Directory of Open Access Journals (Sweden)

    Rosario Nicoletti

    2018-01-01

    Full Text Available Boosted by the general aim of exploiting the biotechnological potential of the microbial component of biodiversity, research on the secondary metabolite production of endophytic fungi has remarkably increased in the past few decades. Novel compounds and bioactivities have resulted from this work, which has stimulated a more thorough consideration of various natural ecosystems as conducive contexts for the discovery of new drugs. Thriving at the frontier between land and sea, mangrove forests represent one of the most valuable areas in this respect. The present paper offers a review of the research on the characterization and biological activities of secondary metabolites from manglicolous strains of species belonging to the genus Talaromyces. Aspects concerning the opportunity for a more reliable identification of this biological material in the light of recent taxonomic revisions are also discussed.

  15. Identification of Microbial Metabolites Elevating Vitamin Contents in Barley Seeds.

    Science.gov (United States)

    Yousaf, Anam; Qadir, Abdul; Anjum, Tehmina; Ahmad, Aqeel

    2015-08-19

    The current investigation analyzes metabolites of Acetobacter aceti to explore chemical compounds responsible for the induction of vitamins in barley seeds. A bioactivity guided assay of bacterial extracts and chromatographic analyses of barley produce revealed 13 chemical compounds, which were subjected to principal component analysis (PCA). PCA determined four chemical compounds (i.e., quinolinic acid, pyridoxic acid, p-aminobenzoate, and α-oxobutanoic acid) highly associated with increased quantities of vitamins. Further experimentations confirmed that quinolinic acid and p-aminobenzoate were the most efficient vitamin inducers. The results indicated chloroform/ethanol (4:1) as the best solvent system for the extraction of active compounds from crude metabolites of A. aceti. Significant quantities of mevalonic acid were detected in the extracted fraction, indicating the possible induction of the isoprenoid pathway. Altogether, the current investigation broadens the frontiers in plant-microbe interaction.

  16. Radioimmunossay of hormones and metabolites in blood serum and plasma

    International Nuclear Information System (INIS)

    Khare, G.P.

    1978-01-01

    Hormones or metabolites which are capable of producing antibodies can be detected and precisely quantitated by this method. Antibodies, to various hormones or metabolites whose assay is desired, are adsorbed onto commercially available imitation or cultured pearls. These pearls coated with antibody are contacted with a buffered reaction mixture containing blood serum or plasma specimen and respective radioactive antigen. The entire reaction is allowed to proceed for a time sufficient to form antigen (radioactive or non-radioactive)-antibody complex. These complexes on the pearls are washed and the total amount of radioactivity emanating from the complex is measured. This is indicative of the extent of binding of radioactive antigen and provides an indirect correlation of the amount of non-radioactive antigen present in the serum or plasma sample

  17. Glucosinolate metabolites required for an Arabidopsis innate immune response.

    Science.gov (United States)

    Clay, Nicole K; Adio, Adewale M; Denoux, Carine; Jander, Georg; Ausubel, Frederick M

    2009-01-02

    The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity and is defined partly by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen-triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen-triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens.

  18. Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response*

    Science.gov (United States)

    Clay, Nicole K.; Adio, Adewale M.; Denoux, Carine; Jander, Georg; Ausubel, Frederick M.

    2008-01-01

    Summary The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity, and is defined in part by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens. PMID:19095898

  19. Typology of secondary cyanobacterial metabolites from minimum spanning tree analysis.

    Science.gov (United States)

    Guyot, M; Doré, J C; Devillers, J

    2004-04-01

    Recently, two main events have spurred a rapid increase in cyanobacteria chemical, toxicological, and ecological research. The first deals with the interest in isolating compounds from these organisms as source of active products with potential therapeutic applications. The second pertains the crucial problem of harmful cyanobacterial blooms in the aquatic environments. In this context, 594 secondary metabolites belonging to more than 30 genera of cyanobacteria were retrieved from literature. In order to perform their typology, they were first associated with 87 different molecular archetypes and two orphan classes. These 89 groups of molecular structures were then confronted to minimum spanning tree analysis. Attempts were made to graphically derive chemotaxonomical relationships. The interest of QSAR models for estimating the potential pharmacological interest of the cyanobacterial secondary metabolites was also discussed.

  20. Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review

    International Nuclear Information System (INIS)

    Wiegand, C.; Pflugmacher, S.

    2005-01-01

    Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Many of them are able to produce a wide range of toxic secondary metabolites. These cyanobacterial toxins can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production of secondary metabolites and endotoxins, which could be toxic to animals and plants. Many of the freshwater cyanobacterial blooms include species of the toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ in mechanisms of uptake, affected organs, and molecular mode of action. In this review, the main focus is the aquatic environment and the effects of these toxins to the organisms living there. Some basic toxic mechanisms will be discussed in comparison to the mammalian system

  1. Abiotic stresses as tools for metabolites in microalgae.

    Science.gov (United States)

    Paliwal, Chetan; Mitra, Madhusree; Bhayani, Khushbu; Bharadwaj, S V Vamsi; Ghosh, Tonmoy; Dubey, Sonam; Mishra, Sandhya

    2017-11-01

    Microalgae, due to various environmental stresses, constantly tune their cellular mechanisms to cope with them. The accumulation of the stress metabolites is closely related to the changes occurring in their metabolic pathways. The biosynthesis of metabolites can be triggered by a number of abiotic stresses like temperature, salinity, UV- radiation and nutrient deprivation. Although, microalgae have been considered as an alternative sustainable source for nutraceutical products like pigments and omega-3 polyunsaturated fatty acids (PUFAs) to cater the requirement of emerging human population but inadequate biomass generation makes the process economically impractical. The stress metabolism for carotenoid regulation in green algae is a 2-step metabolism. There are a few major stresses which can influence the formation of phycobiliprotein in cyanobacteria. This review would primarily focus on the cellular level changes under stress conditions and their corresponding effects on lipids (including omega-3 PUFAs), pigments and polymers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health.

    Science.gov (United States)

    Cervenka, Igor; Agudelo, Leandro Z; Ruas, Jorge L

    2017-07-28

    Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia. Conversely, kynurenine accumulation can be suppressed by activating kynurenine clearance in exercised skeletal muscle. The effect of exercise training on depression through modulation of the kynurenine pathway highlights an important mechanism of interorgan cross-talk mediated by these metabolites. Here, we discuss peripheral mechanisms of tryptophan-kynurenine metabolism and their effects on inflammatory, metabolic, oncologic, and psychiatric disorders. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. Nutrient intake, digestibility and rumen metabolites in bulls fed rice ...

    African Journals Online (AJOL)

    Nutrient intake, digestibility and rumen metabolites were determined in rumen - cannulated bulls fed rice straw or straw supplemented with urea, groundnut hay or cotton seed cake. Total dry matter intake (DMI) ranged from 7.55 Lo 8.29kg/d or 3.66 to 4.04% of liveweight and from 6.48 to 7. 21 kg/d for organic matter.

  4. Steroid receptor profiling of vinclozolin and its primary metabolites

    International Nuclear Information System (INIS)

    Molina-Molina, Jose-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernandez, Mariana-Fatima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolas; Balaguer, Patrick

    2006-01-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR >> PR > GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process

  5. Antimicrobial efficacy of secondary metabolites from Glomerella cingulata

    OpenAIRE

    Hara Kishore, K.; Misra, Sunil; Ramesh Chandra, D.; Prakash, K.V.V. R.; Suryanarayana Murty, U.

    2007-01-01

    Fungi are known to produce a vast array of secondary metabolites that are gaining importance for their biotechnological applications. Early reports suggest that G. cingulata has the capability to transform many compounds by various enzymatic actions. Therefore, the focus of this study was to determine the antibacterial and antifungal activity of crude ethyl acetate extract of G. cingulata using agar cup bioassay method. Crude extract of G. cingulata exhibited remarkable antifungal activity ag...

  6. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack

    Science.gov (United States)

    Huber, Meret; Epping, Janina; Schulze Gronover, Christian; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Köllner, Tobias G.; Vogel, Heiko; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A. M.; Verhoeven, Koen; Preite, Veronica; Gershenzon, Jonathan; Erb, Matthias

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground. PMID:26731567

  7. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack.

    Directory of Open Access Journals (Sweden)

    Meret Huber

    2016-01-01

    Full Text Available Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg. decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha, and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.

  8. Pleiotropic mechanisms facilitated by resveratrol and its metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Calamini, Barbara; Ratia, Kiira; Malkowski, Michael G.; Cuendet, Muriel; Pezzuto, John M.; Santarsiero, Bernard D.; Mesecar, Andrew D. (Geneva); (Hawaii); (SUNYB); (UIC)

    2010-07-01

    Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD{sup +}-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensively metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4{prime}-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4?-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo an interplay between resveratrol and its metabolites with different molecular targets may be responsible for the overall beneficial health effects previously attributed only to resveratrol itself.

  9. Secondary Metabolites from Inula britannica L. and Their Biological Activities

    Directory of Open Access Journals (Sweden)

    Yoon-Ha Kim

    2010-03-01

    Full Text Available Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica.

  10. Secondary metabolites from Inula britannica L. and their biological activities.

    Science.gov (United States)

    Khan, Abdul Latif; Hussain, Javid; Hamayun, Muhammad; Gilani, Syed Abdullah; Ahmad, Shabir; Rehman, Gauhar; Kim, Yoon-Ha; Kang, Sang-Mo; Lee, In-Jung

    2010-03-10

    Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids) and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica.

  11. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack.

    Science.gov (United States)

    Huber, Meret; Epping, Janina; Schulze Gronover, Christian; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Köllner, Tobias G; Vogel, Heiko; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A M; Verhoeven, Koen; Preite, Veronica; Gershenzon, Jonathan; Erb, Matthias

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.

  12. Chemoenzymatic Preparation and Biophysical Properties of Sulfated Quercetin Metabolites

    Czech Academy of Sciences Publication Activity Database

    Valentová, Kateřina; Káňová, Kristýna; Di Meo, F.; Pelantová, Helena; Chambers, Christopher S.; Rydlová, Lenka; Petrásková, Lucie; Křenková, Alena; Cvačka, Josef; Trouillas, P.; Křen, Vladimír

    2017-01-01

    Roč. 18, č. 11 (2017), č. článku 2231. E-ISSN 1422-0067 R&D Projects: GA MŠk(CZ) LD15082; GA MŠk LTC17009; GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : quercetin * sulfotransferase * metabolites Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.226, year: 2016

  13. Cytotoxicity of luteolin in primary rat hepatocytes: the role of CYP3A-mediated ortho-benzoquinone metabolite formation and glutathione depletion.

    Science.gov (United States)

    Shi, Fuguo; Zhao, Peng; Li, Xiaobing; Pan, Hong; Ma, Shiping; Ding, Li

    2015-11-01

    Luteolin (LUT), an active ingredient in traditional Chinese medicines and an integral part of the human diet, has shown promising pharmacological activities with a great potential for clinical use. The purpose of this study was to evaluate the role of cytochrome P450 (CYP450)-mediated reactive ortho-benzoquinone metabolites formation and glutathione (GSH) depletion in LUT-induced cytotoxicity in primary rat hepatocytes. A reactive ortho-benzoquinone metabolite was identified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in rat liver microsomes (RLMs) and rat hepatocytes. Using a specific chemical inhibitor method, the CYP3A subfamily was found to be responsible for the reactive metabolite formation in RLMs. Induction of CYP3A by dexamethasone enhanced LUT-induced cytotoxicity, whereas inhibition of CYP3A by ketoconazole (Keto) decreased the cytotoxicity. The cytotoxicity and cell apoptosis induced by LUT were related to the amount of reactive metabolite formation. Furthermore, Keto inhibited the LUT-induced GSH exhaustion. The cytotoxicity was significantly enhanced by pretreatment with L-buthionine sulfoximine to deplete the intracellular GSH. A time course experiment showed that GSH depletion by LUT was not via oxidation of GSH and occurred prior to the increase in 2', 7'-dichlorofluorescein in hepatocytes. Collectively, these data suggest that CYP3A-mediated reactive metabolite formation plays a critical role in LUT-induced hepatotoxicity, and the direct GSH depletion is an initiating event in LUT-mediated cytotoxicity in primary rat hepatocytes. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Secondary Metabolites Produced during the Germination of Streptomyces coelicolor

    Directory of Open Access Journals (Sweden)

    Matouš Čihák

    2017-12-01

    Full Text Available Spore awakening is a series of actions that starts with purely physical processes and continues via the launching of gene expression and metabolic activities, eventually achieving a vegetative phase of growth. In spore-forming microorganisms, the germination process is controlled by intra- and inter-species communication. However, in the Streptomyces clade, which is capable of developing a plethora of valuable compounds, the chemical signals produced during germination have not been systematically studied before. Our previously published data revealed that several secondary metabolite biosynthetic genes are expressed during germination. Therefore, we focus here on the secondary metabolite production during this developmental stage. Using high-performance liquid chromatography-mass spectrometry, we found that the sesquiterpenoid antibiotic albaflavenone, the polyketide germicidin A, and chalcone are produced during germination of the model streptomycete, S. coelicolor. Interestingly, the last two compounds revealed an inhibitory effect on the germination process. The secondary metabolites originating from the early stage of microbial growth may coordinate the development of the producer (quorum sensing and/or play a role in competitive microflora repression (quorum quenching in their nature environments.

  15. Urinary Kinetics of Heroin Metabolites in Pigs Shortly After Intake.

    Science.gov (United States)

    Høiseth, Gudrun; Gottås, André; Berg, Thomas; Arnestad, Marianne; Halvorsen, Per Steinar; Bachs, Liliana C

    2017-06-01

    In previous experimental studies on heroin metabolites excretion in urine, the first sample was often collected a few hours after intake. In forensic cases, it is sometimes questioned if a positive urine result is expected e.g., 30 min after intake. The aim of this study was to investigate urinary excretion of heroin metabolites (morphine, 6-monoacetylmorphine (6-MAM) and morphine-3-glucuronide (M3G)) every 30 min until 330 min after injection of a 20 mg heroin dose in six pigs. Samples were analyzed using a previously published, fully validated liquid chromatography-tandem mass spectrometry method. All metabolites were detected after 30 min in all pigs. The time to maximum concentration (Tmax) median (range) for 6-MAM and morphine was 30 min (first sample) (30-120), and 90 min (30-330) for M3G. In four of the six pigs, the Tmax of 6-MAM and morphine was reached within 30 min. All analytes were still detectable at the end of study. This study showed that positive results in urine are expected to be seen shortly after use of heroin in pigs. Detection times were longer than previously indicated, especially for 6-MAM, but previous studies used lower doses. As the physiology of these animals resembles that of the humans, transferability to man is expected. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Evidence for biological denitrification inhibition (BDI) by plant secondary metabolites.

    Science.gov (United States)

    Bardon, Clément; Piola, Florence; Bellvert, Floriant; Haichar, Feth el Zahar; Comte, Gilles; Meiffren, Guillaume; Pommier, Thomas; Puijalon, Sara; Tsafack, Noelline; Poly, Franck

    2014-11-01

    Previous studies on the effect of secondary metabolites on the functioning of rhizosphere microbial communities have often focused on aspects of the nitrogen (N) cycle but have overlooked biological denitrification inhibition (BDI), which can affect plant N-nutrition. Here, we investigated the BDI by the compounds of Fallopia spp., an invasive weed shown to be associated with a low potential denitrification of the soil. Fallopia spp. extracts were characterized by chromatographic analysis and were used to test the BDI effects on the metabolic and respiratory activities of denitrifying bacteria, under aerobic and anaerobic (denitrification) conditions. The BDI of Fallopia spp. extracts was tested on a complex soil community by measuring denitrification enzyme activity (DEA), substrate induced respiration (SIR), as well as abundances of denitrifiers and total bacteria. In 15 strains of denitrifying bacteria, extracts led to a greater BDI (92%) than respiration inhibition (50%). Anaerobic metabolic activity reduction was correlated with catechin concentrations and the BDI was dose dependent. In soil, extracts reduced the DEA/SIR ratio without affecting the denitrifiers: total bacteria ratio. We show that secondary metabolite(s) from Fallopia spp. inhibit denitrification. This provides new insight into plant-soil interactions and improves our understanding of a plant's ability to shape microbial soil functioning. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  17. Importance of Secondary Metabolites for Leaf Beetles (Coleoptera: Chrysomelidae

    Directory of Open Access Journals (Sweden)

    A. N. EKİZ

    2014-06-01

    Full Text Available Leaf beetles (Chrysomelidae are one of the most diverse families of herbivorous insects. Many of them are important agricultural pests and cause remarkable loss of crop and money as well. Plant leaves and roots are primary food source of both larva and adults of leaf beetles. Plants produce many secondary metabolites in reaction to herbivore insects. It is a well-known phenomenon that quantity and variety of secondary metabolites in plant leaves may change in response to insect attacks. Herbivore insects have to deal with such defensive secondary chemicals and overcome either by detoxifying or storing them. Accordingly, many specialist herbivores coevolved with their host plant. Certain phenolic glycosides may reduce leaf beetle feeding. Condensed tannins are anti-herbivore defenses against leaf chewing beetles, including leaf beetles. Flavonoid compounds are feeding deterrents for many flea leaf beetles. Cinnamic acid derivatives are other known feeding deterrents for leaf beetles. Secondary metabolites quantity and nutritional quality of host plants are not only important for feeding but also for providing enemy-free space and suitable oviposition sites.

  18. Crude oil metabolites in groundwater at two spill sites

    Science.gov (United States)

    Bekins, Barbara A.; Cozzarelli, Isabelle M.; Erickson, Melinda L.; Steenson, Ross; Thorn, Kevin A.

    2016-01-01

    Two groundwater plumes in north central Minnesota with residual crude oil sources have 20 to 50 mg/L of nonvolatile dissolved organic carbon (NVDOC). These values are over 10 times higher than benzene and two to three times higher than Diesel Range Organics in the same wells. On the basis of previous work, most of the NVDOC consists of partial transformation products from the crude oil. Monitoring data from 1988 to 2015 at one of the sites located near Bemidji, MN show that the plume of metabolites is expanding toward a lakeshore located 335 m from the source zone. Other mass balance studies of the site have demonstrated that the plume expansion is driven by the combined effect of continued presence of the residual crude oil source and depletion of the electron accepting capacity of solid phase iron oxide and hydroxides on the aquifer sediments. These plumes of metabolites are not covered by regulatory monitoring and reporting requirements in Minnesota and other states. Yet, a review of toxicology studies indicates that polar metabolites of crude oil may pose a risk to aquatic and mammalian species. Together the results suggest that at sites where residual sources are present, monitoring of NVDOC may be warranted to evaluate the fates of plumes of hydrocarbon transformation products.

  19. Environmental behavior of sulfadiazine, sulfamethazine, and their metabolites.

    Science.gov (United States)

    Biošić, Martina; Mitrevski, Marija; Babić, Sandra

    2017-04-01

    Sulfonamides are one of the most frequently used antibiotics worldwide. Therefore, processes that determine their fate in the environment are of great interest. In the present work, biodegradation as biotic process and hydrolysis and photolysis as abiotic processes were investigated. In biodegradation experiments, it was found out that sulfonamides (sulfadiazine and sulfamethazine) and their N 4 -acetylated metabolites were not readily biodegradable. The results showed that decrease of concentrations were in the range from 4% for sulfadiazine to 22% for N 4 -acetylsulfamethazine. Hydrolytic experiments examined at pH values normally found in the environment also showed their resistance. However, photolysis proved to be significant process for decreasing concentrations of sulfonamides and their metabolites in three various aqueous matrices (Milli-Q water, river water, and synthetic wastewater). In addition, influence of ubiquitous water constituents (Cl - , NO 3 - , SO 4 2- , PO 4 3- , and humic acids) was also investigated, showing their different impact on photolysis of investigated pharmaceuticals. The results showed that photolysis followed first-order kinetics in all cases. The obtained results are very important for assesing the environmental fate of sulfonamides and their metabolites in the aquatic environment.

  20. Plant products and secondary metabolites with acaricide activity against ticks.

    Science.gov (United States)

    Rosado-Aguilar, J A; Arjona-Cambranes, K; Torres-Acosta, J F J; Rodríguez-Vivas, R I; Bolio-González, M E; Ortega-Pacheco, A; Alzina-López, A; Gutiérrez-Ruiz, E J; Gutiérrez-Blanco, E; Aguilar-Caballero, A J

    2017-04-30

    The present review documents the results of studies evaluating the acaricidal activity of different plant products and secondary metabolites against ticks that are resistant and susceptible to conventional acaricides. Studies published from 1998 to 2016 were included. The acaricidal activity of plant extracts, essential oils and secondary compounds from plants have been evaluated using bioassays with ticks in the larval and adult stages. There is variable effectiveness according to the species of plant and the concentrations used, with observed mortalities ranging from 5 to 100% against the Rhipicephalus (Boophilus), Amblyomma, Dermacentor, Hyalomma, and Argas genera. A number of plants have been reported to cause high mortalities and/or affect the reproductive capacity of ticks in the adult phase. In the majority of these trials, the main species of plants evaluated correspond to the families Lamiaceae, Fabaceae, Asteraceae, Piperaceae, Verbenaceae, and Poaceae. Different secondary metabolites such as thymol, carvacrol, 1,8-cineol and n-hexanal, have been found to be primarily responsible for the acaricidal activity of different essential oils against different species of ticks, while nicotine, dibenzyldisulfide and dibenzyltrisulfide have been evaluated for plant extracts. Only thymol, carvacrol and 1,8-cineol have been evaluated for acaricidal activity under in vivo conditions. The information in the present review allows the conclusion that the secondary metabolites contained in plant products could be used as an alternative for the control of ticks that are susceptible or resistant to commercial acaricides. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Urinary phthalate metabolite concentrations in girls with premature thelarche.

    Science.gov (United States)

    Durmaz, Erdem; Erkekoglu, Pinar; Asci, Ali; Akçurin, Sema; Bircan, İffet; Kocer-Gumusel, Belma

    2018-03-17

    In girls, breast development before eight years of age is called "premature thelarche (PT)". There are few studies in literature that show the interaction between PT and phthalate exposure. The aim of this study was to determine the urinary levels of di-(2-ethylhexyl) phthalate (DEHP) metabolites and other phthalate metabolites in girls with PT. PT group consisted of 29 newly diagnosed subjects. Control group comprised of healthy age-matched girls (n = 25). Urinary phthalate metabolite concentrations were measured by liquid chromatography/tandem mass spectroscopy (LC-MS/MS). The urinary concentrations of mono-(2-ethyl-hexyl)phthalate (MEHP) in the PT group (33.96 ± 6.88 μg/g creatinine) were found to be significantly higher compared to control group (11.54 ± 1.39 μg/g creatinine, p = 0.002). In PT group, %MEHP was also markedly higher vs. control (17.84 ± 3.31 vs. 6.44 ± 1.13, p = 0.001). Our results suggest that DEHP is more efficiently converted to MEHP in girls with PT, the importance of which needs to be further elucidated. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Pharmacokinetic studies of 131 I-stevioside and his metabolites

    International Nuclear Information System (INIS)

    Cardoso, V.N.

    1993-01-01

    Stevia rebaudiana is a shrub widely in Paraguay and Brazil, belonging to the compositae family. The leaves of this plant contain large amounts of stevioside. Since the use of stevioside as sugar substitute continues to increase, the purpose of this study is to investigate the biological distribution, excretion and the possibility of stevioside to be degraded to steviol 'in vitro'. 131 -I-stevioside (1,10 MBq) was i.v. injected in Wistar male rats its distribution in the body and metabolism were studied. The highest concentration of radioactivity was observed in the liver and the small intestine after 10 and 120 minutes respectively. RP-HPLC analysis of the bile showed that steviol appeared as a major metabolite, representing 47,3% of the radioactivity while stevioside represented 37,3% and the remaining 15,4% was due to an unidentified metabolite. The results showed that stevioside was partially degraded 'in vivo' to steviol and other metabolite, and that part of the radioactivity was absorbed from the small intestine. (author)

  3. The radioimmunological determination of glibenclamide and its metabolites in serum

    International Nuclear Information System (INIS)

    Glogner, P.; Heni, N.; Nissen, L.

    1977-01-01

    This report describes a sensitive and specific radio-immunological method for determining serum levels of the 1-(p-[2- (5-chloro-2-methoxybenzamido) -ethyl]-benzenesulfonyl) -3-cyclohexylurea (clibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide. (orig.) [de

  4. Oviposition response of the mosquito, Culex quinquefasciatus to the secondary metabolite(s of the fungus, Trichoderma viride

    Directory of Open Access Journals (Sweden)

    Geetha I

    2003-01-01

    Full Text Available Secondary metabolites produced by Trichoderma viride, a deuteromycetes fungus, under submerged culture condition were formulated and evaluated for oviposition attractancy against gravid females of Culex quinquefasciatus mosquito. At a concentration of 10 µg ml-1 the formulation showed remarkable attractancy with an oviposition active index (OAI of +0.52. When the oviposition attractancy of the formulation was compared with a known oviposition attractant, p-cresol, both at 10 µg ml-1, the former was found to be more attractive to result in 70% egg laying than the later with 30% egg laying. Thin layer chromatography fractions of the secondary metabolites showed that a fraction with Rf value of 0.88 was highly active as oviposition attractant with an OAI of +0.65. Further work on identification of the active principle(s of the microbial formulation might lead to an oviposition attractant useful in mosquito vector management.

  5. Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

    Science.gov (United States)

    Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

    2010-03-01

    In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number

  6. Alterations of urinary metabolite profile in model diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  7. Alterations of urinary metabolite profile in model diabetic nephropathy

    International Nuclear Information System (INIS)

    Stec, Donald F.; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

    2015-01-01

    Highlights: • 1 H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in

  8. Drug repositioning for enzyme modulator based on human metabolite-likeness.

    Science.gov (United States)

    Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

    2017-05-31

    Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for

  9. Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moran, Jeffery H. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Department of Public Health, Public Health Laboratory, Little Rock, AR 72205 (United States); Prather, Paul L., E-mail: pratherpaull@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2013-06-01

    K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018

  10. Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

    International Nuclear Information System (INIS)

    Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.; Moran, Jeffery H.; Prather, Paul L.

    2013-01-01

    K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB 1 Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB 2 Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB 2 Rs (hCB 2 Rs). The affinity of cannabinoids for hCB 2 Rs was determined by competition binding studies employing CHO-hCB 2 membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB 2 cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB 2 Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB 2 Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ 9 -tetrahydrocannabinol (Δ 9 -THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB 2 R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB 2 Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB 2 Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB 1 and CB 2 Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2

  11. Tip enhancement

    CERN Document Server

    Kawata, Satoshi

    2007-01-01

    This book discusses the recent advances in the area of near-field Raman scattering, mainly focusing on tip-enhanced and surface-enhanced Raman scattering. Some of the key features covered here are the optical structuring and manipulations, single molecule sensitivity, analysis of single-walled carbon nanotubes, and analytic applications in chemistry, biology and material sciences. This book also discusses the plasmonic materials for better enhancement, and optical antennas. Further, near-field microscopy based on second harmonic generation is also discussed. Chapters have been written by some of the leading scientists in this field, who present some of their recent work in this field.·Near-field Raman scattering·Tip-enhanced Raman spectroscopy·Surface-enhanced Raman spectroscopy·Nano-photonics·Nanoanalysis of Physical, chemical and biological materials beyond the diffraction limits·Single molecule detection

  12. Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites

    Science.gov (United States)

    Rombouts, Caroline; Hemeryck, Lieselot Y.; Van Hecke, Thomas; De Smet, Stefaan; De Vos, Winnok H.; Vanhaecke, Lynn

    2017-01-01

    Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N’-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases. PMID:28195169

  13. Effect of Glomus mosseae and plant growth promoting rhizomicroorganisms (PGPR's on growth, nutrients and content of secondary metabolites in Begonia malabarica Lam.

    Directory of Open Access Journals (Sweden)

    Thangavel Selvaraj

    2008-10-01

    Full Text Available Begonia malabarica Lam. (Begoniaceae is one of the important medicinal plants whose main secondary metabolites are luteolin, quercetin and β-sitosterol. The leaves are used for the treatment of respiratory tract infections, diarrhoea, blood cancer and skin diseases. A study was undertaken to determine the effect of arbuscular mycorrhizal (AM fungus, Glomus mosseae, and some plant growth promoting rhizomicro-organisms (PGPR's on the growth, biomass, nutrients, and content of secondary metabolites of B. malabarica plant under green house conditions. Various plant growth parameters (total plant biomass, mycorrhizal parameter, shoot and root phosphorus, mineral content (potassium, iron, zinc, and copper, and secondary metabolites (total phenols, ortho-dihydroxy phenols, tannins, flavonoids, and alkaloids were determined and found to vary with different treatments. Among all the treatments, plants inoculated with 'microbial consortium' consisting of Glomus mosseae + Bacillus coagulans + Trichoderma viride performed better than with other treatments or uninoculated control plants. The results of this experiment clearly indicated that inoculation of B. malabarica with G. mosseae along with PGPR's enhanced its growth, biomass yield, nutrients and secondary metabolites.

  14. A diet rich in high-glucoraphanin broccoli interacts with genotype to reduce discordance in plasma metabolite profiles by modulating mitochondrial function123

    Science.gov (United States)

    Armah, Charlotte N; Traka, Maria H; Dainty, Jack R; Defernez, Marianne; Janssens, Astrid; Leung, Wing; Doleman, Joanne F; Potter, John F

    2013-01-01

    Background: Observational and experimental studies suggest that diets rich in cruciferous vegetables and glucosinolates may reduce the risk of cancer and cardiovascular disease (CVD). Objective: We tested the hypothesis that a 12-wk dietary intervention with high-glucoraphanin (HG) broccoli would modify biomarkers of CVD risk and plasma metabolite profiles to a greater extent than interventions with standard broccoli or peas. Design: Subjects were randomly assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk and 347 plasma metabolites were quantified before and after the intervention. Results: No significant differences in the effects of the diets on biomarkers of CVD risk were found. Multivariate analyses of plasma metabolites identified 2 discrete phenotypic responses to diet in individuals within the HG broccoli arm, differentiated by single nucleotide polymorphisms associated with the PAPOLG gene. Univariate analysis showed effects of sex (P broccoli arm, the consequence of the intervention was to reduce variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines between the 2 PAPOLG genotypes. Conclusions: The metabolic changes observed with the HG broccoli diet are consistent with a rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of fatty acid β-oxidation with TCA cycle activity. These modifications may contribute to the reduction in cancer risk associated with diets that are rich in cruciferous vegetables. This trial was registered at clinicaltrials.gov as NCT01114399. PMID:23964055

  15. Tentative Structural Assignment of a Glucuronide Metabolite of Methyltestosterone in Tilapia Bile by Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Nishshanka, Upul; Chu, Pak-Sin; Evans, Eric; Reimschuessel, Renate; Hasbrouck, Nicholas; Amarasinghe, Kande; Jayasuriya, Hiranthi

    2015-06-24

    Methyltestosterone (MT), a strong androgenic steroid, is not approved for use in fish aquaculture in the United States. It is used in the U.S. under an investigational new animal drug exemption (INAD) only during the early life stages of fish. There is a possibility that farmers feed fish with MT to enhance production for economic gains. Therefore, there is a need to develop methods for the detection of MT and its metabolite residues in fish tissue for monitoring purposes. Previously, our laboratory developed a liquid chromatography-quadrupole time-of-flight (LC-QTOF) method for characterization of 17-O-glucuronide metabolite (MT-glu) in bile of tilapia dosed with MT. The system used was an Agilent 6530 Q-TOF equipped with electrospray jet stream technology, operating in positive ion mode. Retrospective analysis of the data generated in that experiment by a feature-finding algorithm, combined with a search against an in-house library of possible MT-metabolites, resulted in the discovery of a major glucuronide metabolite of MT in the bile extracts. Preliminary data indicate it to be a glucuronide of a hydroxylated MT (OHMT-glu) which persists in tilapia bile for at least 2 weeks after dosing. We present the tentative structural assignment of the OHMT-glu in tilapia bile and time course of development. This glucuronide can serve as a marker to monitor illegal use of MT in tilapia culture.

  16. UV-B radiation modulates physiology and lipophilic metabolite profile in Olea europaea.

    Science.gov (United States)

    Celeste Dias, Maria; Pinto, Diana C G A; Correia, Carlos; Moutinho-Pereira, José; Oliveira, Helena; Freitas, Helena; Silva, Artur M S; Santos, Conceição

    2018-03-01

    Ultraviolet-B (UV-B) radiation plays an important role in plant photomorphogenesis. Whilst the morpho-functional disorders induced by excessive UV irradiation are well-known, it remains unclear how this irradiation modulates the metabolome, and which metabolic shifts improve plants' tolerance to UV-B. In this study, we use an important Mediterranean crop, Olea europaea, to decipher the impacts of enhanced UV-B radiation on the physiological performance and lipophilic metabolite profile. Young olive plants (cv. 'Galega Vulgar') were exposed for five days to UV-B biologically effective doses of 6.5 kJ m -2  d -1 and 12.4 kJ m -2 d -1 . Cell cycle/ploidy, photosynthesis and oxidative stress, as well as GC-MS metabolites were assessed. Both UV-B treatments impaired net CO 2 assimilation rate, transpiration rate, photosynthetic pigments, and RuBisCO activity, but 12.4 kJ m -2  d -1 also decreased the photochemical quenching (qP) and the effective efficiency of PSII (Φ PSII ). UV-B treatments promoted mono/triperpene pathways, while only 12.4 kJ m -2  d -1 increased fatty acids and alkanes, and decreased geranylgeranyl-diphosphate. The interplay between physiology and metabolomics suggests some innate ability of these plants to tolerate moderate UV-B doses (6.5 kJ m -2  d -1 ). Also their tolerance to higher doses (12.4 kJ m -2  d -1 ) relies on plants' metabolic adjustments, where the accumulation of specific compounds such as long-chain alkanes, palmitic acid, oleic acid and particularly oleamide (which is described for the first time in olive leaves) play an important protective role. This is the first study demonstrating photosynthetic changes and lipophilic metabolite adjustments in olive leaves under moderate and high UV-B doses. Copyright © 2018 Elsevier GmbH. All rights reserved.

  17. Photodegradation of sulfasalazine and its human metabolites in water by UV and UV/peroxydisulfate processes.

    Science.gov (United States)

    Ji, Yuefei; Yang, Yan; Zhou, Lei; Wang, Lu; Lu, Junhe; Ferronato, Corinne; Chovelon, Jean-Marc

    2018-04-15

    The widespread occurrence of pharmaceuticals and their metabolites in natural waters has raised great concerns about their potential risks on human health and ecological systems. This study systematically investigates the degradation of sulfasalazine (SSZ) and its two human metabolites, sulfapyridine (SPD) and 5-aminosalicylic acid (5-ASA), by UV and UV/peroxydisulfate (UV/PDS) processes. Experimental results show that SPD and 5-ASA were readily degraded upon UV 254 nm direct photolysis, with quantum yields measured to be (8.6 ± 0.8) × 10 -3 and (2.4 ± 0.1) × 10 -2  mol Einstein -1 , respectively. Although SSZ was resistant to direct UV photolysis, it could be effectively removed by both UV/H 2 O 2 and UV/PDS processes, with fluence-based pseudo-first-order rate constants determined to be 0.0030 and 0.0038 cm 2  mJ -1 , respectively. Second-order rate constant between SO 4 •- and SSZ was measured as (1.33 ± 0.01) × 10 9  M -1 s -1 by competition kinetic method. A kinetic model was established for predicting the degradation rate of SSZ in the UV/PDS process. Increasing the dosage of PDS significantly enhanced the degradation of SSZ in the UV/PDS process, which can be well predicted by the developed kinetic model. Natural water constituents, such as natural organic matter (NOM) and bicarbonate (HCO 3 - ), influenced the degradation of SSZ differently. The azo functional group of SSZ molecule was predicted as the reactive site susceptible to electrophilic attack by SO 4 •- by frontier electron densities (FEDs) calculations. Four intermediate products arising from azo bond cleavage and SO 2 extrusion were identified by solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry (SPE-LC-MS/MS). Based on the products identified, detailed transformation pathways for SSZ degradation in the UV/PDS system were proposed. Results reveal that UV/PDS could be an efficient approach for remediation of water

  18. Light-induced biochemical variations in secondary metabolite production and antioxidant activity in callus cultures of Stevia rebaudiana (Bert).

    Science.gov (United States)

    Ahmad, Naveed; Rab, Abdur; Ahmad, Nisar

    2016-01-01

    Stevia rebaudiana (S. rebaudiana) is a very important species with worldwide medicinal and commercial uses. Light is one of the major elicitors that fluctuate morphogenic potential and biochemical responses. In the present study, we investigated the effect of various spectral lights on biomass accumulation and secondary metabolite production in callus cultures of S. rebaudiana. Leaf explants were placed on Murashige and Skoog (MS) medium and exposed to various spectral lights. 6-Benzyle adenine (BA) and 2, 4-dichlorophenoxy acetic acid (2, 4-D; 2.0 mgl(-1)) were used for callus induction. The control light (16/8h) produced optimum callogenic response (92.73%) than other colored lights. Compared to other colored lights, control grown cultures displayed maximum biomass accumulation (5.78 gl(-1)) during a prolonged log phase at the 18th day of growth kinetics. Cultures grown under blue light enhanced total phenolic content (TPC; 102.32 μg/g DW), total flavonoid content (TFC; 22.07 μg/g DW) and total antioxidant capacity (TAC; 11.63 μg/g DW). On the contrary, green and red lights improved reducing power assay (RPA; 0.71Fe(II)g(-1) DW) and DPPH-radical scavenging activity (DRSA; 80%). Herein, we concluded that the utilization of colored lights is a promising strategy for enhanced production of antioxidant secondary metabolites in callus cultures of S. rebaudiana. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Contribution of phlA and some metabolites of fluorescent pseudomonads to antifungal activity.

    Science.gov (United States)

    Afsharmanesh, H; Ahmadzadeh, M; Sharifi-Tehrani, A; Javan-Nikkhah, M; Ghazanfari, K

    2005-01-01

    Fluorescent Pseudomonas species are an important group of PGPR that suppress fungal root and seedling disease by production of antifungal metabolites such as 2,4-diacetylphloroglucinol (2,4-DAPG), pyoluteorin, pyrolinitrin, siderophores and HCN. The compound 2,4-DAPG is a major determinant in biocontrol of plant pathogens. A 7.2 kbp chromosomal DNA region, carrying DAPG biosynthetic genes (phlA, phlC, phlB, phlD, phIE and phlF). Detecting the ph1 genes make them an ideal marker gene for 2,4-DAPG-producing fluorescent pseudomonad's. In this study we detected ph1A gene (that convert MAPG to 2,4-DAPG) using PCR assay with primers phlA-1r and phlA- f that enabled amplification of phlA sequences from fluorescent pseudomonad's from ARDRA group 1 and 3. We could detect phlA gene in P. fluorescens strains CHAO, Pf-44, Pf-1, Pf-2, Pf-3, Pf-17, Pf-62 and Pf-64, native isolates of Iran. The efficacy of this method for rapid assay characterizing rhizosphere population of 2,4-DAPG producing bacteria from soil of different area of Iran is in progress. We used a collection of 48 fluorescent pseudomonas strains in vitro, with known biological control activity against some soil born phytopathogenic fungi such as, Macrophomina phaseoli, Rhizoctonia solani Vericillium dahlia, Phytophthora nicotiana, Pythium spp. and Fusarium spp. and the potential to produce known secondary metabolites such as protease. Strains Pf-1, Pf-2, Pf-3, Pf-17, Pf-33 and Pf-44 showed the best antifungal activity against all fungi used in this study. Thirty-eight of 48 strains produced protease. The ability to rapidly characterize populations of 2,4-DAPG producers will greatly enhance our understanding of their role in the suppression of root disease.

  20. The enzyme toxicity and genotoxicity of chlorpyrifos and its toxic metabolite TCP to zebrafish Danio rerio.

    Science.gov (United States)

    Wang, Jun; Wang, Jinhua; Zhu, Lusheng; Xie, Hui; Shao, Bo; Hou, Xinxin

    2014-12-01

    Chlorpyrifos is a broad-spectrum organophosphorus insecticide (O,O-diethyl -O-3,5,6-trichloro-2-pyridyl phosphorothioate) that is used in numerous agricultural and urban pest controls. The primary metabolite of chlorpyrifos is 3,5,6-trichloro pyridine-2-phenol (TCP). Because of its strong water solubility and mobility, this harmful metabolite exists in the environment in a large amount. Although TCP has potentially harmful effects on organisms in the environment, few studies have addressed TCP pollution. Therefore, this study was undertaken to investigate the effect of chlorpyrifos and TCP on the microsomal cytochrome P450 content in the liver, on the activity of NADPH-P450 reductase and antioxidative enzymes [catalase (CAT) and superoxide dismutase (SOD)], and on reactive oxygen species (ROS) generation and DNA damage in zebrafish. Male and female zebrafish were separated and exposed to a control solution and three concentrations of chlorpyrifos (0.01, 0.1, 1 mg L(-1)) and TCP (0.01, 0.1, 0.5 mg L(-1)), respectively, sampled after 5, 10, 15, 20 and 25 days. The results indicated that the P450 content and the NADPH-P450 reductase and antioxidative enzyme (CAT and SOD) activities could be induced by chlorpyrifos and TCP. DNA damage of zebrafish was enhanced with increasing chlorpyrifos and TCP concentrations. Meanwhile, chlorpyrifos and TCP induced a significant increase of ROS generation in the zebrafish hepatopancreas. In conclusion, this study proved that chlorpyrifos (0.01-1 mg L(-1)) and TCP (0.01-0.5 mg L(-1)) are both highly toxic to zebrafish.

  1. Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

    Directory of Open Access Journals (Sweden)

    Orozco Helena

    2012-08-01

    Full Text Available Abstract Background Viability in a non dividing state is referred to as chronological life span (CLS. Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content.

  2. An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes.

    Science.gov (United States)

    Ota, Ajda; Ulrih, Nataša P

    2017-01-01

    Diabetes mellitus is a common effect of uncontrolled high blood sugar and it is associated with long-term damage, dysfunction, and failure of various organs. In the adult population, the global prevalence of diabetes has nearly doubled since 1980. Without effective prevention and management programs, the continuing significant rise in diabetes will have grave consequences on the health and lifespan of the world population, and also on the world economy. Supplements can be used to correct nutritional deficiencies or to maintain an adequate intake of certain nutrients. These are often used as treatments for diabetes, sometimes because they have lower costs, or are more accessible or "natural" compared to prescribed medications. Several vitamins, minerals, botanicals, and secondary metabolites have been reported to elicit beneficial effects in hypoglycemic actions in vivo and in vitro ; however, the data remain conflicting. Many pharmaceuticals commonly used today are structurally derived from natural compounds from traditional medicinal plants. Botanicals that are most frequently used to help manage blood glucose include: bitter melon ( Momordica charantia ), fenugreek ( Trigonella foenum graecum ), gurmar ( Gymnema sylvestre ), ivy gourd ( Coccinia indica ), nopal ( Opuntia spp.), ginseng, Russian tarragon ( Artemisia dracunculus ), cinnamon ( Cinnamomum cassia ), psyllium ( Plantago ovata ), and garlic ( Allium sativum ). In majority of the herbal products and secondary metabolites used in treating diabetes, the mechanisms of action involve regulation of insulin signaling pathways, translocation of GLUT-4 receptor and/or activation the PPARγ. Several flavonoids inhibit glucose absorption by inhibiting intestinal α-amylase and α-glucosidase. In-depth studies to validate the efficacies and safeties of extracts of these traditional medicinal plants are needed, and large, well designed, clinical studies need to be carried out before the use of such preparations can

  3. 77 FR 32401 - 2,6-Diisopropylnaphthalene (2,6-DIPN) and Its Metabolites and Degradates; Pesticide Tolerances

    Science.gov (United States)

    2012-06-01

    ...-Diisopropylnaphthalene (2,6-DIPN) and Its Metabolites and Degradates; Pesticide Tolerances AGENCY: Environmental...,6- Diisopropylnaphthalene (2,6-DIPN) and it's metabolites and degradates in or on certain... metabolites and degradates, 2,6- DIPN and its metabolites and degradates, in or on potato, granules/flakes at...

  4. Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy.

    Science.gov (United States)

    Watanabe, Shimpei; Kuzhiumparambil, Unnikrishnan; Fu, Shanlin

    2018-03-08

    The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans. UR-144 was incubated with C. elegans for 72 h, and the resulting metabolites were chromatographically separated. Six fractions were collected and analysed by NMR spectroscopy. UR-144 was also incubated with human liver microsomes (HLM), and the liquid chromatography-high resolution mass spectrometry analysis was performed on the HLM metabolites with the characterised fungal metabolites as reference standards. Ten metabolites were characterised by NMR analysis including dihydroxy metabolites, carboxy and hydroxy metabolites, a hydroxy and ketone metabolite, and a carboxy and ketone metabolite. Of these metabolites, dihydroxy metabolite, carboxy and hydroxy metabolites, and a hydroxy and ketone metabolite were identified in HLM incubation. The results indicate that the fungus is capable of producing human-relevant metabolites including the exact isomers. The capacity of the fungus C. elegans to allow for NMR structural characterisation by enabling production of large amounts of metabolites makes it an ideal model to complement metabolism studies.

  5. Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

    Directory of Open Access Journals (Sweden)

    Carmine Vecchione

    2017-05-01

    Full Text Available The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA, the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS, and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS. LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

  6. Rapid identification of herbal compounds derived metabolites using zebrafish larvae as the biotransformation system.

    Science.gov (United States)

    Wang, Chen; Yin, Ying-Hao; Wei, Ying-Jie; Shi, Zi-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

    2017-09-15

    Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds. Two pivotal steps involved in this strategy are to differentiate metabolites from herbal compounds and match metabolites with their parent compounds. The differentiation step was achieved by cross orthogonal partial least-squares discriminant analysis. Automatic matching analysis was performed on R Project based on a self-developed program, of which the number of matched ionic clusters and its corresponding percentage between metabolite and parent compound were taken into account to assess their similarity. Using this strategy, 46 metabolites screened from incubation water samples of zebrafish treated with total Epimedium flavonoids (EFs) could be matched with their corresponding parent compounds, 37 of them were identified and validated by the known metabolic pathways and fragmentation patterns. Finally, 75% of the identified EFs metabolites were successfully detected in urine samples of rats treated with EFs. These experimental results indicate that the proposed strategy using zebrafish larvae as the biotransformation system will facilitate the rapid identification of metabolites derived from herbal compounds, which shows promising perspectives in providing additional resources for pharmaceutical developments from natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network

    Science.gov (United States)

    Yao, Qianlan; Xu, Yanjun; Yang, Haixiu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Sun, Zeguo; Shi, Xinrui; Feng, Li; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

    2015-01-01

    The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. PMID:26598063

  8. Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

    Science.gov (United States)

    Liu, Li; Wen, Yan; Zhang, Lei; Xu, Peng; Liang, Xiao; Du, Yanan; Li, Ping; He, Awen; Fan, QianRui; Hao, Jingcan; Wang, Wenyu; Guo, Xiong; Shen, Hui; Tian, Qing; Zhang, Feng; Deng, Hong-Wen

    2018-03-01

    Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now. To explore the relationship between blood metabolites and osteoporosis. We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. Genome-wide SNP genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a published whole-genome sequencing study. For each subject, the genetic risk score (GRS) of metabolite was calculated from the genotype data of metabolite associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential impact of blood metabolites on the variations bone phenotypes. 10,000 permutations were conducted to calculate the empirical P value and false discovery rate (FDR). 481 blood metabolites were analyzed in this study. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol(1,5-AG) (Pdiscovery metabolites on the variations of BMD, and identified several candidate blood metabolites for osteoporosis.

  9. SyGMa: combining expert knowledge and empirical scoring in the prediction of metabolites.

    Science.gov (United States)

    Ridder, Lars; Wagener, Markus

    2008-05-01

    Predictions of potential metabolites based on chemical structure are becoming increasingly important in drug discovery to guide medicinal chemistry efforts that address metabolic issues and to support experimental metabolite screening and identification. Herein we present a novel rule-based method, SyGMa (Systematic Generation of potential Metabolites), to predict the potential metabolites of a given parent structure. A set of reaction rules covering a broad range of phase 1 and phase 2 metabolism has been derived from metabolic reactions reported in the Metabolite Database to occur in humans. An empirical probability score is assigned to each rule representing the fraction of correctly predicted metabolites in the training database. This score is used to refine the rules and to rank predicted metabolites. The current rule set of SyGMa covers approximately 70 % of biotransformation reactions observed in humans. Evaluation of the rule-based predictions demonstrated a significant enrichment of true metabolites in the top of the ranking list: while in total, 68 % of all observed metabolites in an independent test set were reproduced by SyGMa, a large part, 30 % of the observed metabolites, were identified among the top three predictions. From a subset of cytochrome P450 specific metabolites, 84 % were reproduced overall, with 66 % in the top three predicted phase 1 metabolites. A similarity analysis of the reactions present in the database was performed to obtain an overview of the metabolic reactions predicted by SyGMa and to support ongoing efforts to extend the rules. Specific examples demonstrate the use of SyGMa in experimental metabolite identification and the application of SyGMa to suggest chemical modifications that improve the metabolic stability of compounds.

  10. Combined effects of O3 and UV radiation on secondary metabolites and endogenous hormones of soybean leaves.

    Science.gov (United States)

    Mao, Bing; Yin, Hong; Wang, Yan; Zhao, Tian-Hong; Tian, Rong-Rong; Wang, Wei; Ye, Jia-Shu

    2017-01-01

    Enhanced ultraviolet radiation (UV) and elevated tropospheric ozone (O3) may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day) and enhanced UV radiation (1.73 kJ h-1 m-2) significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone.

  11. Combined effects of O3 and UV radiation on secondary metabolites and endogenous hormones of soybean leaves.

    Directory of Open Access Journals (Sweden)

    Bing Mao

    Full Text Available Enhanced ultraviolet radiation (UV and elevated tropospheric ozone (O3 may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day and enhanced UV radiation (1.73 kJ h-1 m-2 significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone.

  12. Chemoenzymatic Preparation and Biophysical Properties of Sulfated Quercetin Metabolites

    Directory of Open Access Journals (Sweden)

    Kateřina Valentová

    2017-10-01

    Full Text Available Sulfated quercetin derivatives are important authentic standards for metabolic studies. Quercetin-3′-O-sulfate, quercetin-4′-O-sulfate, and quercetin-3-O-sulfate as well as quercetin-di-O-sulfate mixture (quercetin-7,3′-di-O-sulfate, quercetin-7,4′-di-O-sulfate, and quercetin-3′,4′-di-O-sulfate were synthetized by arylsulfotransferase from Desulfitobacterium hafniense. Purified monosulfates and disulfates were fully characterized using MS and NMR and tested for their 1,1-diphenyl-2-picrylhydrazyl (DPPH, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+ and N,N-dimethyl-p-phenylenediamine (DMPD radical scavenging, Folin-Ciocalteau reduction (FCR, ferric reducing antioxidant power (FRAP, and anti-lipoperoxidant activities in rat liver microsomes damaged by tert-butylhydroperoxide. Although, as expected, the sulfated metabolites were usually less active than quercetin, they remained still effective antiradical and reducing agents. Quercetin-3′-O-sulfate was more efficient than quercetin-4′-O-sulfate in DPPH and FCR assays. In contrast, quercetin-4′-O-sulfate was the best ferric reductant and lipoperoxidation inhibitor. The capacity to scavenge ABTS+• and DMPD was comparable for all substances, except for disulfates, which were the most efficient. Quantum calculations and molecular dynamics simulations on membrane models supported rationalization of free radical scavenging and lipid peroxidation inhibition. These results clearly showed that individual metabolites of food bioactives can markedly differ in their biological activity. Therefore, a systematic and thorough investigation of all bioavailable metabolites with respect to native compounds is needed when evaluating food health benefits.

  13. Novel urinary metabolite signature for diagnosing postpartum depression

    Directory of Open Access Journals (Sweden)

    Lin L

    2017-05-01

    Full Text Available Lin Lin, Xiao-mei Chen, Rong-hua Liu Department of Obstetrics and Gynecology, Linyi People’s Hospital, Shandong, People’s Republic of China Background: Postpartum depression (PPD could affect ~10% of women and impair the quality of mother–infant interactions. Currently, there are no objective methods to diagnose PPD. Therefore, this study was conducted to identify potential biomarkers for diagnosing PPD.Materials and methods: Morning urine samples of PPD subjects, postpartum women without depression (PPWD and healthy controls (HCs were collected. The gas chromatography-mass spectroscopy (GC-MS-based urinary metabolomic approach was performed to characterize the urinary metabolic profiling. The orthogonal partial least-squares-discriminant analysis (OPLS-DA was used to identify the differential metabolites. The logistic regression analysis and Bayesian information criterion rule were further used to identify the potential biomarker panel. The receiver operating characteristic curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker panel.Results: Totally, 73 PPD subjects, 73 PPWD and 74 HCs were included, and 68 metabolites were identified using GC-MS. The OPLS-DA model showed that there were 22 differential metabolites (14 upregulated and 8 downregulated responsible for separating PPD subjects from HCs and PPWD. Meanwhile, a panel of five potential biomarkers – formate, succinate, 1-methylhistidine, a-glucose and dimethylamine – was identified. This panel could effectively distinguish PPD subjects from HCs and PPWD with an area under the curve (AUC curve of 0.948 in the training set and 0.944 in the testing set.Conclusion: These results demonstrated that the potential biomarker panel could aid in the future development of an objective diagnostic method for PPD. Keywords: postpartum depression, gas chromatography-mass spectroscopy, biomarker, metabolomics

  14. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.

    Science.gov (United States)

    van der Vegt, Bea J; Lieuwes, Natasja; Cremers, Thomas I F H; de Boer, Sietse F; Koolhaas, Jaap M

    2003-09-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.

  15. Unbiased Evaluation of Bioactive Secondary Metabolites in Complex Matrices

    Science.gov (United States)

    Inui, Taichi; Wang, Yuehong; Pro, Samuel M.; Franzblau, Scott G.; Pauli, Guido F.

    2012-01-01

    The majority of bioactive principles in a complex matrix such as natural products and botanical medicines are secondary rather than primary metabolites. In addition to being chemically diverse, the bioactivity of an ethnobotanical can comprise from one to several bioactive compounds, present in a complex mixture. Conventional discovery efforts utilize bioassay-guided fractionation (BGF) to isolate individual active compounds. When applied to complex natural products, BGF is often challenged by an apparent loss of activity during fractionation, resulting in weakly active isolated compounds. Metabolomic analysis can potentially complement existing the BGF paradigm by capturing the chemical complexity of the metabolites. The proposed biochemometric approach establishes a link between the chemistry of a secondary metabolome and a deserved health impact, using a high-throughput, high-resolution capable biological endpoint. The proof of principle is demonstrated for the anti-tuberculosis (TB) activity of the Alaskan ethnobotanical, Oplopanax horridus. Biochemometric analysis identified the 100 most active constituents from thousands of metabolites in the active extract by means of 2D orthogonal chromatography using countercurrent and GC-MS methods. Previously isolated O. horridus phytoconstituents were used as reference markers of known structure and bio(in)activity. Positive correlations allowed distinction of anti-TB actives from inactive compounds. A total of 29 bioactives from 3 main structural classes were assigned based on MS data. Biochemometric analysis is a new tool for the standardization of herbal medicines and ethnobotanicals, as well as for drug discovery from nature. The method can assign multiple active compounds in complex mixtures without their prior isolation or structure elucidation, while still providing an interface to structural information. PMID:22766306

  16. Solubilities and toxicities of condensed thiophenes and their microbial metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Seymour, D. T.; Hrudey, S. E.; Fedorak, P. M. [Alberta Univ., Edmonton, AB (Canada)

    1995-12-31

    A method to assess the reduction in toxicity of contaminants as a measure of the effectiveness of a bioremediation program was described. Condensed thiophenes are commonly found in petroleum and creosote, and some of these compounds have been found to persist in crude oil-contaminated environments. To help identify these bacterial products several of the metabolites were chemically synthesized and tested for toxicity, using the Microtox method. Part 1 of the study measured the toxicity of twelve organosulphur compounds; Part 2 determined the aqueous solubilities of the parent compounds and the synthesized metabolites; Part 3 measured the changes in toxicity that occurred in batch cultures of Pseudomonas strain F grown in the presence of selected condensed thiophenes. The aqueous solubility measurements gave results that agreed well with those found in the literature; i.e., each polar metabolite was more soluble than its parent compound. The Microtox assays showed that the available pure compounds that are known to be microbial oxidation products were less toxic than their parent compounds. Microtox assays of cultures of Pseudomonas strain F grown in the presence of condensed thiophenes showed no increase in toxicity. Indeed, the growth of cultures detoxified each of the four compounds tested. While all of these results suggest that microbial transformations of condensed thiophenes reduce the toxicity of these compounds, they cannot be accepted as fully reliable because no single test can give a complete picture of the spectrum of toxicity related to these compounds. A broad range of tests, ideally on different trophic levels, is required for a complete assessment. 38 refs., 1 fig.

  17. Microbial metabolite of dimethylarsinic acid is highly toxic and genotoxic

    International Nuclear Information System (INIS)

    Kuroda, Koichi; Yoshida, Kaoru; Yoshimura, Mieko; Endo, Yoko; Wanibuchi, Hideki; Fukushima, Shoji; Endo, Ginji

    2004-01-01

    Dimethylarsinic acid [DMA, (CH 3 ) 2 AsO(OH)] causes cancer in the urinary bladder of rats. However, its mechanism of cancer or the ultimate carcinogenic form is not yet known. Rats administered dimethylarsinic acid excrete three unknown arsenic compounds (termed M-1, M-2, and M-3) in urine or feces, and these compounds are presumed to be produced by intestinal bacteria. Escherichia coli A3-6 isolated from a rat yielded two unknown arsenic compounds (M-2 and M-3) from dimethylarsinic acid and M-1 from trimethylarsine oxide (TMAO) in the presence of cysteine (Cys). Contents of M-2 and M-3 varied with cysteine concentration. The cytotoxicity and genotoxicity of the bacteria-free solution of dimethylarsinic acid or trimethylarsine oxide metabolized by E. coli A3-6 were studied using V79 cells. Dimethylarsinic acid (1 mM) metabolized by E. coli A3-6 in the presence of cysteine (1 mM) was highly cytotoxic (50% survival reduction concentration; 2.1 μM As) in V79 cells, and the toxic substance appeared to be M-2. The metabolite solution (at 2.5-10 μM total As) induced c-mitosis and tetraploids, and caused mitotic arrest, since it increased mitotic cells at the cytotoxic dose. The metabolite solution also significantly increased sister chromatid exchange (SCE) and chromosomal aberrations, most of which were chromatid gaps and chromatid breaks. A3-6 converted 96.1% of trimethylarsine oxide to M-1 in the presence of cysteine. This metabolite solution did not exhibit cytotoxicity or genotoxicity. The reported M-2 concentration in urine of rats administered levels of DMA via drinking water known to cause bladder tumors was sufficient to exhibit cytotoxic and genotoxic effects in urinary bladder. Thus, we hypothesize that intestinal bacteria play an important role in carcinogenicity of dimethylarsinic acid

  18. Secondary Metabolites Production by Solid-State Fermentation

    Directory of Open Access Journals (Sweden)

    Barrios-González, J.

    2005-01-01

    Full Text Available Microbial secondary metabolites are useful high value products with an enormous range of biological activities. Moreover, the past two decades have been a phase of rapid discovery of new activities and development of major compounds for use in different industrial fields, mainly pharmaceuticals, cosmetics, food, agriculture and farming. Many of these metabolites could be produced advantageously in industry by solid–state fermentation (SSF. Two types of SSF can be distinguished, depending on the nature of the solid phase used: 1 Solid cultures of one support-substrate phase in which solid phase is constituted by a material that assumes, simultaneously, the functions of support and of nutrients source; and 2 Solid cultures of two substrate-support phases: solid phase is constituted by an inert support impregnated with a liquid medium. Besides good production performance, two phases systems have provided a convenient model for basic studies. Studies in our laboratory, as well as in others, have shown that physiology of idiophase (production phase in SSF share several similarities with the physiology in liquid medium, so similar strategies must be adapted for efficient production processes. However, our studies indicate the need to develop special strains for SSF since overproducing strains, generated for liquid fermentation, cannot be relied upon to perform well in SSF. On the other hand, there are important parameters, specific for SSF, that have to be optimized (pretreatment, initial moisture content, medium concentration and aeration. Respiration studies of secondary metabolites SSF, performed in our laboratory, have shown more subtle aspects of efficient production in SSF. This indicates that there are certain particularities of physiology in SSF that represent the point that needs a better understanding, and that promise to generate knowledge that will be the basis for efficient processes development and control strategies, as well as for

  19. Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats.

    Science.gov (United States)

    Wakabayashi, Masato; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Igarashi, Yasuyuki; Kihara, Akio

    2017-03-01

    Olmsted syndrome (OS) is a congenital dermatosis characterized by palmoplantar keratoderma and periorificial keratotic plaque. TRPV3 (transient receptor potential vanilloid subtype 3) encodes a thermosensitive Ca 2+ channel and is the causative gene of OS. However, the molecular mechanism that causes the pathological development of OS is unclear. We aimed to investigate the molecular mechanisms underlying OS pathology from the perspective of lipid metabolism. Comprehensive lipidomics and microarray analyses were conducted on tissue samples from a non-lesional skin area of OS model rats (Ht rats) and from wild type (WT) rats as the control. Infiltration of leukocytes such as eosinophils and neutrophils and an increase in the fibrotic region were detected in the unaffected skin area of Ht rats compared with the WT rats. Among about 600 lipid species examined, the levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides decreased by ≥16-fold in Ht rats compared with WT rats. Consistent with the decreases in the 15-LOX metabolites, expression levels of the genes that encode the 15-LOXs, Alox15 and Alox15b, were largely reduced. Conversely, increased expression levels were detected of Il36b, Ccl20, Cxcl1, and Cxcl2, which encode cytokines/chemokines, and S100a8 and S100a9, which encode the Ca 2+ binding proteins that are implicated in epidermal proliferation. The pro-inflammatory state in the unaffected skin of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  20. Secondary Metabolites from the Soft Coral Sinularia arborea

    Directory of Open Access Journals (Sweden)

    Ping-Jyun Sung

    2013-09-01

    Full Text Available Previous studies on the chemical constituents of soft corals belonging to the genus Sinularia have led to the isolation of a number of interesting secondary metabolites and some of these were found to possess extensive bioactivities [1–3]. Continuation investigation on the chemical constituents of the marine invertebrates collected off the waters of Taiwan, two new cembrane-type diterpenoids, arbolides A (1 and B (2, and a known steroid, crassarosterol A (3 [4], were isolated from the soft coral Sinularia arborea (family Alcyonacea (Figure 1. In this paper, we describe the isolation, structure determination and cytotoxicity of compounds 1–3.

  1. Fungal endophytes - secret producers of bioactive plant metabolites.

    Science.gov (United States)

    Aly, A H; Debbab, A; Proksch, P

    2013-07-01

    The potential of endophytic fungi as promising sources of bioactive natural products continues to attract broad attention. Endophytic fungi are defined as fungi that live asymptomatically within the tissues of higher plants. This overview will highlight the uniqueness of endophytic fungi as alternative sources of pharmaceutically valuable compounds originally isolated from higher plants, e.g. paclitaxel, camptothecin and podophyllotoxin. In addition, it will shed light on the fungal biosynthesis of plant associated metabolites as well as new approaches developed to improve the production of commercially important plant derived compounds with the involvement of endophytic fungi.

  2. Screening Senyawa Metabolit Sekunder Pada Fungi Laut Emericella Nidulans

    Directory of Open Access Journals (Sweden)

    Irah Namirah

    2016-01-01

    Full Text Available Abstract: Investigation bioactive secondary metabolite previously, Research Center for Marine and Fisheries Product Processing and Biotechnology found anticancer properties to Emericella nidulans marine fungi strain MFW39 isolated from ascidia Aplidium longithorax collected from Wakatobi Marine National Park. Emestrin was a compound with an ETP (epipolithiodioxopiperazine group that found in Emericella nidulans marine fungi have cytotoxicity properties. Emestrin show cytotoxic activity to breast cancer cell line [T47D], cancer cervic cell line [HeLa], colon cancer cell line [WiDr] and liver cancer cell line (HepG2. The aim of the research to investigated other derivative of emestrin compound. The screening with UPLC (Ultra Performance Liquid Chromatography mass analysis q-TOF/MS (quadrupole-Time of Flight/Mass spectra positif mode (ES+.. Monoisotopic ion Derivative compound of emestrin that detected from (ES+ UPLC-ESI-qTOF-MS spectrum are emestrin B, emestrin C. Another compound that detected are cytochalasin B dan C.Keywords: Emericella nidulans, Emestrin, Emestrin derivative, UPLC- q-TOF/MS spectrum Abstrak: Pada penelitian pencarian metabolit sekunder bioaktif sebelumnya, Balai Besar Riset Pengolahan Produk dan Bioteknologi Kelautan dan Perikanan menemukan fungi Emericella nidulans strain MFW39 yang diisolasi dari ascidia Aplidium longithorax dari Taman Nasional Laut Wakatobi, Sulawesi tenggara memiliki aktivitas sitotoksik terhadap beberapa sel kanker, diantaranya sel turunan kanker payudara (T47D, liver (HepG2, kanker usus (C28 dan serviks (HeLa. Senyawa yang berkontribusi terhadap sifat sitotoksik adalah senyawa emestrin yang memiliki gugus ETP (epipolithiodioxopiperazine. Hasil isolasi dan karakterisasi senyawa bioaktif yang ditemukan pada fungi Emericella nidulans strain MFW39 adalah senyawa emestrin. Penelitian ini bertujuan mencari derivat senyawa emestrin lain. Proses screening dilakukan dengan mencari puncak monoisotopik senyawa

  3. Gut microbiomes and their metabolites shape human and animal health.

    Science.gov (United States)

    Park, Woojun

    2018-03-01

    The host genetic background, complex surrounding environments, and gut microbiome are very closely linked to human and animal health and disease. Although significant correlations between gut microbiota and human and animal health have been revealed, the specific roles of each gut bacterium in shaping human and animal health and disease remain unclear. However, recent omics-based studies using experimental animals and surveys of gut microbiota from unhealthy humans have provided insights into the relationships among microbial community, their metabolites, and human and animal health. This editorial introduces six review papers that provide new discoveries of disease-associated microbiomes and suggest possible microbiome-based therapeutic approaches to human disease.

  4. Rapid detection of drug metabolites in latent fingermarks.

    Science.gov (United States)

    Hazarika, Pompi; Jickells, Sue M; Russell, David A

    2009-01-01

    Magnetic particles functionalised with anti-cotinine antibody have been used to image latent fingermarks through the detection of the cotinine antigen in the sweat deposited within the fingerprints of smokers. The antibody-magnetic particle conjugates are readily applied to latent fingerprints while excess reagents are removed through the use of a magnetic wand. The results have shown that drug metabolites, such as cotinine, can be detected and used to image the fingermark to establish the identity of an individual within 15 minutes.

  5. Two New Secondary Metabolites from the Endophytic Fungus Endomelanconiopsis endophytica

    Directory of Open Access Journals (Sweden)

    Zhang-Hua Sun

    2016-07-01

    Full Text Available Two new secondary metabolites, endomeketals A–B (1–2, a new natural product (3, and a known compound (4 were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta. Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. However, no compound showed cytotoxic activity against these human tumor cell lines.

  6. Secondary metabolites and biological activity of Pentas species: A minireview

    Directory of Open Access Journals (Sweden)

    Heba-tollah M. Sweelam

    2018-03-01

    Full Text Available The genus Pentas belongs to the Rubiaceae family, which contains approximately 40 species. Several Pentas species were reported to be used as a folk treatment by African indigenous people in treating some diseases such as malaria, tapeworms, dysentery, gonorrhea, syphilis and snake poisoning. This article covers the period from 1962 to 2017 and presents an overview of the biological activity of different Pentas species and describes their phytochemical traits. As a conclusion, the main secondary metabolites from Pentas species are quinones, highly oxygenated chromene-based structures, and iridoids. Pentas species are widely used in folk medicine but they have to be more investigated for their medicinal properties.

  7. Discovery of novel secondary metabolites in Aspergillus aculeatus

    DEFF Research Database (Denmark)

    Petersen, Lene Maj; Holm, Dorte Koefoed; Gotfredsen, Charlotte Held

    2012-01-01

    Polyketides (PKs) and non-ribosomal peptides (NRPs) constitute large classes of diverse secondary metabolites (SMs) and are important sources for pharmaceuticals due to their structural diversity and wide variety of biological activities. Our investigation of the chemical profile...... on the USERTM cloning technique. The AMA-1 based gene expression has successfully been applied to express genes in A. aculeatus and by this approach the function of a PKS gene has been established. Furthermore the technique was used to activate a silent cluster by expression of a transcription factor, leading...

  8. Secondary metabolite toxins and nutrition of plant pathogenic fungi.

    Science.gov (United States)

    Howlett, Barbara J

    2006-08-01

    Fungal pathogens derive nutrition from the plants they invade. Some fungi can subvert plant defence responses such as programmed cell death to provide nutrition for their growth and colonisation. Secondary metabolite toxins produced by fungi often play a role in triggering these responses. Knowledge of the biosynthesis of these toxins, and the availability of fungal genome sequences and gene disruption techniques, allows the development of tools for experiments aimed at discovering the role of such toxins in triggering plant cell death and plant disease.

  9. Effect of fertilisation and harvest period on polar metabolites of Calendula oficcinalis

    Directory of Open Access Journals (Sweden)

    Eduardo Felipe Alves Fernandes

    Full Text Available The present study evaluated the chemical profile of polar extracts of Calendula officinalis L., Asteraceae, that were grown under different cultivation conditions: chemical fertilisation, organic fertilisation and mulching. Furthermore, we investigated metabolite variations during plant development by comparing the metabolites from harvested plants at 60 and 120 days after planting. We used HPLC-DAD-MS/MS to tentatively identify metabolites. In total, we identified seven known compounds: five flavonoid glycosides and two caffeoylquinic acids derivatives. There were no statistically significant differences in the expression of metabolites from plants grown under the examined soil treatments. However, five substances varied according to harvest time, suggesting that the biosynthesis of polar metabolites of Calendula officinalis is not affected by changes in soil composition. Therefore, this plant could represent a source for phytomedicines with a constant content of polar metabolites.

  10. In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

    International Nuclear Information System (INIS)

    Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

    1989-01-01

    Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

  11. Bacterial metabolism in immediate response to nutritional perturbation with temporal and network view of metabolites.

    Science.gov (United States)

    Yukihira, Daichi; Fujimura, Yoshinori; Wariishi, Hiroyuki; Miura, Daisuke

    2015-09-01

    In this study, the initial propagation of metabolic perturbation in Escherichia coli was visualized to understand the dynamic characteristics of the metabolic pathways without the association of transcription alterations. E. coli cells were exposed to the sudden relief of glucose starvation, and time-dependent variances in metabolite balances were traced in the second scale. The acquired time-course data were represented by structural variations of the metabolite-metabolite correlation network. The initial correlation structure was altered immediately by the glucose pulse, followed by further structural variations within a few minutes. It was demonstrated that one metabolite temporally correlated with distinct metabolites with different timings, and such a behavior could imply a regulatory role for the metabolite in the metabolic network. Centrality analysis of the networks and partial correlation analysis indicated that preparation for growth and oxidative stress could be coupled as a structural property of the metabolic pathways.

  12. GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

    Directory of Open Access Journals (Sweden)

    Carter Steve G

    2010-03-01

    Full Text Available Abstract Background This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM. In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cultures were grown. The culture supernatant was harvested as a source of metabolites (MTB, and the bacteria were used to isolate cell wall fragments (CW. Both of these fractions were compared in a series of in vitro assays. Results Both MTB and CW inhibited spontaneous and oxidative stress-induced ROS formation in human PMN cells and increased the phagocytic activity of PMN cells in response to bacteria-like carboxylated fluorospheres. Both fractions supported random PMN and f-MLP-directed PMN cell migration, indicating a support of immune surveillance and antibacterial defense mechanisms. In contrast, low doses of both fractions inhibited PMN cell migration towards the inflammatory mediators IL-8 and LTB4. The anti-inflammatory activity was strongest for CW, where the PMN migration towards IL-8 was inhibited down to dilutions of 1010. Both MTB and CW induced the expression of the CD69 activation marker on human CD3- CD56+ NK cells, and enhanced the expression of CD107a when exposed to K562 tumor cells in vitro. The fractions directly modulated cytokine production, inducing production of the Th2 cytokines IL-4, IL-6, and IL-10, and inhibiting production of IL-2. Both fractions further modulated mitogen-induced cytokine production in the following manner: Both fractions enhanced the PHA-induced production of IL-6 and reduced the PHA-induced production of TNF-alpha. Both fractions enhanced the PWM-induced production of TNF-alpha and IFN-gamma. In addition, MTB

  13. Sfp-type PPTase inactivation promotes bacterial biofilm formation and ability to enhance wheat drought tolerance

    Directory of Open Access Journals (Sweden)

    Salme eTimmusk

    2015-05-01

    Full Text Available Paenibacillus polymyxa is a common soil bacterium with broad range of practical applications. An important group of secondary metabolites in P. polymyxa are nonribosomal peptide and polyketide derived metabolites (NRP/PK. Modular nonribosomal peptide synthetases catalyse main steps in the biosynthesis of the complex secondary metabolites. Here we report on the inactivation of an A26 sfp-type phosphopantetheinyl transferase. The inactivation of the gene resulted in loss of NRP/PK production. In contrast to the former Bacillus spp. model the mutant strain compared to wild type showed greatly enhanced biofilm formation ability. Its biofilm promotion is directly mediated by NRP/PK, as exogenous addition of the wild type metabolite extracts restores its biofilm formation level. Wheat inoculation with bacteria that had lost their sfp-type PPTase gene resulted in two times higher plant survival and about three times increased biomass under severe drought stress compared to wild type.

  14. A new hydroxytyrosol metabolite identified in human plasma: hydroxytyrosol acetate sulphate.

    Science.gov (United States)

    Rubió, Laura; Macià, Alba; Valls, Rosa M; Pedret, Anna; Romero, Maria-Paz; Solà, Rosa; Motilva, Maria-José

    2012-09-15

    We report progress in the study of olive oil phenolic metabolites in humans and identify a new hydroxytyrosol metabolite called hydroxytyrosol acetate sulphate, which was determined using tandem MS, after ingestion of 30 ml of olive oil with a high phenolic content (500 mg/kg oil), reaching a maximum concentration of 1.63 μM. In order to understand and explain the generation of this metabolite, two different pathways are proposed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian; Andersen, Birgitte; Thrane, Ulf

    2008-01-01

    distribution throughout the fungal kingdom. However, this is the very quality that makes secondary metabolites so useful in classification and identification. Four groups of organisms are particularly good producers of secondary metabolites: plants, fungi, lichen fungi, and actinomycetes, whereas yeasts...... have been analysed for a wide array of terpenes, polyketides, non-ribosomal peptides, and combinations of these. Fungal chemotaxonomy based on secondary metabolites has been used successfully in large ascomycete genera such as Alternaria, Aspergillus, Fusarium, Hypoxylon, Penicillium, Stachybotrys...

  16. MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.

    Science.gov (United States)

    Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2017-01-01

    Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any

  17. Role of wetland organic matters as photosensitizer for degradation of micropollutants and metabolites

    International Nuclear Information System (INIS)

    Lee, Eunkyung; Shon, Ho Kyong; Cho, Jaeweon

    2014-01-01

    Highlights: • Photodegradation of PPCPs was investigated in various NOM enriched solutions. • Direct and indirect photolysis experiments were conducted upon UV irradiation. • PPCPs showed different levels of photodegradation rates depending on their photoreactivity. • Allochthonous NOM inhibited the photolysis of target PPCPs. • Wetland NOM enhanced photodegradation of some conservative PPCPs. - Abstract: Overall photodegradation of pharmaceuticals, personal care products (PPCPs) and pharmaceutical metabolites were investigated in order to evaluate their photochemical fate in aquatic environments in various natural organic matter (NOM) enriched solutions. Tested PPCPs exhibited different rates of loss during direct and indirect photolysis. Here, only ultraviolet (UV) light source was used for direct photolysis and UV together with 3 DOM * for indirect photolysis. Diclofenac and sulfamethoxazole were susceptible to photodegradation, whereas carbamazepine, caffeine, paraxanthine and tri(2-chloroethyl) phosphate (TCEP) showed low levels of photodegradation rate, reflecting their conservative photoreactivity. During indirect photodegradation, in contrast to the hydrophilic autochthonous NOM, allochthonous NOM with relatively high molecular weight (MW), specific ultraviolet absorbance (SUVA) and hydrophobicity (e.g., Suwannee River humic acid (SRHA)) revealed to significantly inhibit the photolysis of target micropollutants. The presence of Typha wetland NOM enhanced the indirect photolysis of well-known conservative micopollutants (carbamazepine and paraxanthine). And atenolol, carbamazepine, glimepiride, and N-acetyl-sulfamethoxazole were found to be sensitive to the triplet excited state of dissolved organic matter ( 3 DOM * ) with Typha wetland NOM under deoxygenated condition. This suggests that photolysis in constructed wetlands connected to the wastewater treatment plant can enhance the degradation of some anthropogenic micropollutants by the

  18. Role of wetland organic matters as photosensitizer for degradation of micropollutants and metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunkyung [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shon, Ho Kyong [School of Civil and Environmental Engineering, University of Technology, Sydney (UTS), PO Box 123, Broadway, Sydney 2007, NSW (Australia); Cho, Jaeweon, E-mail: chojw@yonsei.ac.kr [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

    2014-07-15

    Highlights: • Photodegradation of PPCPs was investigated in various NOM enriched solutions. • Direct and indirect photolysis experiments were conducted upon UV irradiation. • PPCPs showed different levels of photodegradation rates depending on their photoreactivity. • Allochthonous NOM inhibited the photolysis of target PPCPs. • Wetland NOM enhanced photodegradation of some conservative PPCPs. - Abstract: Overall photodegradation of pharmaceuticals, personal care products (PPCPs) and pharmaceutical metabolites were investigated in order to evaluate their photochemical fate in aquatic environments in various natural organic matter (NOM) enriched solutions. Tested PPCPs exhibited different rates of loss during direct and indirect photolysis. Here, only ultraviolet (UV) light source was used for direct photolysis and UV together with {sup 3}DOM{sup *}for indirect photolysis. Diclofenac and sulfamethoxazole were susceptible to photodegradation, whereas carbamazepine, caffeine, paraxanthine and tri(2-chloroethyl) phosphate (TCEP) showed low levels of photodegradation rate, reflecting their conservative photoreactivity. During indirect photodegradation, in contrast to the hydrophilic autochthonous NOM, allochthonous NOM with relatively high molecular weight (MW), specific ultraviolet absorbance (SUVA) and hydrophobicity (e.g., Suwannee River humic acid (SRHA)) revealed to significantly inhibit the photolysis of target micropollutants. The presence of Typha wetland NOM enhanced the indirect photolysis of well-known conservative micopollutants (carbamazepine and paraxanthine). And atenolol, carbamazepine, glimepiride, and N-acetyl-sulfamethoxazole were found to be sensitive to the triplet excited state of dissolved organic matter ({sup 3}DOM{sup *}) with Typha wetland NOM under deoxygenated condition. This suggests that photolysis in constructed wetlands connected to the wastewater treatment plant can enhance the degradation of some anthropogenic micropollutants

  19. Toxicity of Plant Secondary Metabolites Modulating Detoxification Genes Expression for Natural Red Palm Weevil Pesticide Development

    Directory of Open Access Journals (Sweden)

    Ahmed Mohammed AlJabr

    2017-01-01

    Full Text Available This study aimed to explore the larvicidal and growth-inhibiting activities, and underlying detoxification mechanism of red palm weevil against phenylpropanoids, an important class of plant secondary metabolites. Toxicity of α-asarone, eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, coumarin, coumarin 6, coniferyl aldehyde, diniconazole, ethyl cinnamate, and rosmarinic acid was evaluated by incorporation into the artificial diet. All of the phenylpropanoids exhibited dose- and time-dependent insecticidal activity. Among all the tested phenylpropanoids, coumarin exhibited the highest toxicity by revealing the least LD50 value (0.672 g/L. In addition, the most toxic compound (coumarin observed in the current study, deteriorated the growth resulting tremendous reduction (78.39% in efficacy of conversion of digested food (ECD, and (ECI efficacy of conversion of ingested food (70.04% of tenth-instar red palm weevil larvae. The energy-deficient red palm weevil larvae through their intrinsic abilities showed enhanced response to their digestibility resulting 27.78% increase in approximate digestibility (AD compared to control larvae. The detoxification response of Rhynchophorus ferrugineus larvae determined by the quantitative expression of cytochrome P450, esterases, and glutathione S-transferase revealed enhanced expression among moderately toxic and ineffective compounds. These genes especially cytochrome P450 and GST detoxify the target compounds by enhancing their solubility that leads rapid excretion and degradation resulting low toxicity towards red palm weevil larvae. On the other hand, the most toxic (coumarin silenced the genes involved in the red palm weevil detoxification mechanism. Based on the toxicity, growth retarding, and masking detoxification activities, coumarin could be a useful future natural red palm weevil-controlling agent.

  20. Toxicity of Plant Secondary Metabolites Modulating Detoxification Genes Expression for Natural Red Palm Weevil Pesticide Development.

    Science.gov (United States)

    AlJabr, Ahmed Mohammed; Hussain, Abid; Rizwan-Ul-Haq, Muhammad; Al-Ayedh, Hassan

    2017-01-20

    This study aimed to explore the larvicidal and growth-inhibiting activities, and underlying detoxification mechanism of red palm weevil against phenylpropanoids, an important class of plant secondary metabolites. Toxicity of α-asarone, eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, coumarin, coumarin 6, coniferyl aldehyde, diniconazole, ethyl cinnamate, and rosmarinic acid was evaluated by incorporation into the artificial diet. All of the phenylpropanoids exhibited dose- and time-dependent insecticidal activity. Among all the tested phenylpropanoids, coumarin exhibited the highest toxicity by revealing the least LD 50 value (0.672 g/L). In addition, the most toxic compound (coumarin) observed in the current study, deteriorated the growth resulting tremendous reduction (78.39%) in efficacy of conversion of digested food (ECD), and (ECI) efficacy of conversion of ingested food (70.04%) of tenth-instar red palm weevil larvae. The energy-deficient red palm weevil larvae through their intrinsic abilities showed enhanced response to their digestibility resulting 27.78% increase in approximate digestibility (AD) compared to control larvae. The detoxification response of Rhynchophorus ferrugineus larvae determined by the quantitative expression of cytochrome P450 , esterases , and glutathione S-transferase revealed enhanced expression among moderately toxic and ineffective compounds. These genes especially cytochrome P450 and GST detoxify the target compounds by enhancing their solubility that leads rapid excretion and degradation resulting low toxicity towards red palm weevil larvae. On the other hand, the most toxic (coumarin) silenced the genes involved in the red palm weevil detoxification mechanism. Based on the toxicity, growth retarding, and masking detoxification activities, coumarin could be a useful future natural red palm weevil-controlling agent.