WorldWideScience

Sample records for acid metabolism cam

  1. Facultative crassulacean acid metabolism (CAM) plants: powerful tools for unravelling the functional elements of CAM photosynthesis.

    Science.gov (United States)

    Winter, Klaus; Holtum, Joseph A M

    2014-07-01

    Facultative crassulacean acid metabolism (CAM) describes the optional use of CAM photosynthesis, typically under conditions of drought stress, in plants that otherwise employ C3 or C4 photosynthesis. In its cleanest form, the upregulation of CAM is fully reversible upon removal of stress. Reversibility distinguishes facultative CAM from ontogenetically programmed unidirectional C3-to-CAM shifts inherent in constitutive CAM plants. Using mainly measurements of 24h CO2 exchange, defining features of facultative CAM are highlighted in five terrestrial species, Clusia pratensis, Calandrinia polyandra, Mesembryanthemum crystallinum, Portulaca oleracea and Talinum triangulare. For these, we provide detailed chronologies of the shifts between photosynthetic modes and comment on their usefulness as experimental systems. Photosynthetic flexibility is also reviewed in an aquatic CAM plant, Isoetes howellii. Through comparisons of C3 and CAM states in facultative CAM species, many fundamental biochemical principles of the CAM pathway have been uncovered. Facultative CAM species will be of even greater relevance now that new sequencing technologies facilitate the mapping of genomes and tracking of the expression patterns of multiple genes. These technologies and facultative CAM systems, when joined, are expected to contribute in a major way towards our goal of understanding the essence of CAM. PMID:24642847

  2. Modeled hydraulic redistribution in tree-grass, CAM-grass, and tree-CAM associations: the implications of crassulacean acid metabolism (CAM).

    Science.gov (United States)

    Yu, Kailiang; Foster, Adrianna

    2016-04-01

    Past studies have largely focused on hydraulic redistribution (HR) in trees, shrubs, and grasses, and recognized its role in interspecies interactions. HR in plants that conduct crassulacean acid metabolism (CAM), however, remains poorly investigated, as does the effect of HR on transpiration in different vegetation associations (i.e., tree-grass, CAM-grass, and tree-CAM associations). We have developed a mechanistic model to investigate the net direction and magnitude of HR at the patch scale for tree-grass, CAM-grass, and tree-CAM associations at the growing season to yearly timescale. The modeling results show that deep-rooted CAM plants in CAM-grass associations could perform hydraulic lift at a higher rate than trees in tree-grass associations in a relatively wet environment, as explained by a significant increase in grass transpiration rate in the shallow soil layer, balancing a lower transpiration rate by CAM plants. By comparison, trees in tree-CAM associations may perform hydraulic descent at a higher rate than those in tree-grass associations in a dry environment. Model simulations also show that hydraulic lift increases the transpiration of shallow-rooted plants, while hydraulic descent increases that of deep-rooted plants. CAM plants transpire during the night and thus perform HR during the day. Based on these model simulations, we suggest that the ability of CAM plants to perform HR at a higher rate may have different effects on the surrounding plant community than those of plants with C3 or C4 photosynthetic pathways (i.e., diurnal transpiration).

  3. Australia lacks stem succulents but is it depauperate in plants with crassulacean acid metabolism (CAM)?

    Science.gov (United States)

    Holtum, Joseph Am; Hancock, Lillian P; Edwards, Erika J; Crisp, Michael D; Crayn, Darren M; Sage, Rowan; Winter, Klaus

    2016-06-01

    In the flora of Australia, the driest vegetated continent, crassulacean acid metabolism (CAM), the most water-use efficient form of photosynthesis, is documented in only 0.6% of native species. Most are epiphytes and only seven terrestrial. However, much of Australia is unsurveyed, and carbon isotope signature, commonly used to assess photosynthetic pathway diversity, does not distinguish between plants with low-levels of CAM and C3 plants. We provide the first census of CAM for the Australian flora and suggest that the real frequency of CAM in the flora is double that currently known, with the number of terrestrial CAM species probably 10-fold greater. Still unresolved is the question why the large stem-succulent life - form is absent from the native Australian flora even though exotic large cacti have successfully invaded and established in Australia. PMID:27088716

  4. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana.

    Science.gov (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice

    2010-12-15

    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate.

  5. Evolution of a CAM anatomy predates the origins of Crassulacean acid metabolism in the Agavoideae (Asparagaceae).

    Science.gov (United States)

    Heyduk, Karolina; McKain, Michael R; Lalani, Falak; Leebens-Mack, James

    2016-12-01

    Crassulacean acid metabolism (CAM) is a modified form of photosynthesis that has arisen independently at least 35 times in flowering plants. The occurrence of CAM is often correlated with shifts to arid, semiarid, or epiphytic habits, as well as transitions in leaf morphology (e.g. increased leaf thickness) and anatomy (e.g. increased cell size and packing). We assess shifts between C3 and CAM photosynthesis in the subfamily Agavoideae (Asparagaceae) through phylogenetic analysis of targeted loci captured from the nuclear and chloroplast genomes of over 60 species. Carbon isotope data was used as a proxy for mode of photosynthesis in extant species and ancestral states were estimated on the phylogeny. Ancestral character state mapping suggests three independent origins of CAM in the Agavoideae. CAM species differ from C3 species in climate space and are found to have thicker leaves with densely packed cells. C3 ancestors of CAM species show a predisposition toward CAM-like morphology. Leaf characteristics in the ancestral C3 species may have enabled the repeated evolution of CAM in the Agavoideae subfamily. Anatomical changes, including a tendency toward 3D venation, may have initially arisen in C3 ancestors in response to aridity as a way to increase leaf succulence for water storage. PMID:27591171

  6. Day–Night Changes of Energy-rich Compounds in Crassulacean Acid Metabolism (CAM) Species Utilizing Hexose and Starch

    OpenAIRE

    Chen, Li-Song; NOSE, Akihiro

    2004-01-01

    • Background and Aims Plants with crassulacean acid metabolism (CAM) can be divided into two groups according to the major carbohydrates used for malic acid synthesis, either polysaccharide (starch) or monosaccharide (hexose). This is related to the mechanism and affects energy metabolism in the two groups. In Kalanchoë pinnata and K. daigremontiana, which utilize starch, ATP-dependent phosphofructokinase (tonoplast inorganic pyrophosphatase) activity is greater than inorganic pyrophosphate-d...

  7. Climate-resilient agroforestry: physiological responses to climate change and engineering of crassulacean acid metabolism (CAM) as a mitigation strategy.

    Science.gov (United States)

    Borland, Anne M; Wullschleger, Stan D; Weston, David J; Hartwell, James; Tuskan, Gerald A; Yang, Xiaohan; Cushman, John C

    2015-09-01

    Global climate change threatens the sustainability of agriculture and agroforestry worldwide through increased heat, drought, surface evaporation and associated soil drying. Exposure of crops and forests to warmer and drier environments will increase leaf:air water vapour-pressure deficits (VPD), and will result in increased drought susceptibility and reduced productivity, not only in arid regions but also in tropical regions with seasonal dry periods. Fast-growing, short-rotation forestry (SRF) bioenergy crops such as poplar (Populus spp.) and willow (Salix spp.) are particularly susceptible to hydraulic failure following drought stress due to their isohydric nature and relatively high stomatal conductance. One approach to sustaining plant productivity is to improve water-use efficiency (WUE) by engineering crassulacean acid metabolism (CAM) into C3 crops. CAM improves WUE by shifting stomatal opening and primary CO2 uptake and fixation to the night-time when leaf:air VPD is low. CAM members of the tree genus Clusia exemplify the compatibility of CAM performance within tree species and highlight CAM as a mechanism to conserve water and maintain carbon uptake during drought conditions. The introduction of bioengineered CAM into SRF bioenergy trees is a potentially viable path to sustaining agroforestry production systems in the face of a globally changing climate.

  8. Eddy covariance captures four-phase crassulacean acid metabolism (CAM) gas exchange signature in Agave.

    Science.gov (United States)

    Owen, Nick A; Choncubhair, Órlaith Ní; Males, Jamie; Del Real Laborde, José Ignacio; Rubio-Cortés, Ramón; Griffiths, Howard; Lanigan, Gary

    2016-02-01

    Mass and energy fluxes were measured over a field of Agave tequilana in Mexico using eddy covariance (EC) methodology. Data were gathered over 252 d, including the transition from wet to dry periods. Net ecosystem exchanges (FN,EC ) displayed a crassulacean acid metabolism (CAM) rhythm that alternated from CO2 sink at night to CO2 source during the day, and partitioned canopy fluxes (FA,EC ) showed a characteristic four-phase CO2 exchange pattern. Results were cross-validated against diel changes in titratable acidity, leaf-unfurling rates, energy exchange fluxes and reported biomass yields. Projected carbon balance (g C m(-2)  year(-1) , mean ± 95% confidence interval) indicated the site was a net sink of -333 ± 24, of which contributions from soil respiration were +692 ± 7, and FA,EC was -1025 ± 25. EC estimated biomass yield was 20.1 Mg (dry) ha(-1)  year(-1) . Average integrated daily FA,EC was -234 ± 5 mmol CO2  m(-2)  d(-1) and persisted almost unchanged after 70 d of drought conditions. Regression analyses were performed on the EC data to identify the best environmental predictors of FA . Results suggest that the carbon acquisition strategy of Agave offers productivity and drought resilience advantages over conventional semi-arid C3 and C4 bioenergy candidates. PMID:26177873

  9. Eddy covariance captures four-phase crassulacean acid metabolism (CAM) gas exchange signature in Agave.

    Science.gov (United States)

    Owen, Nick A; Choncubhair, Órlaith Ní; Males, Jamie; Del Real Laborde, José Ignacio; Rubio-Cortés, Ramón; Griffiths, Howard; Lanigan, Gary

    2016-02-01

    Mass and energy fluxes were measured over a field of Agave tequilana in Mexico using eddy covariance (EC) methodology. Data were gathered over 252 d, including the transition from wet to dry periods. Net ecosystem exchanges (FN,EC ) displayed a crassulacean acid metabolism (CAM) rhythm that alternated from CO2 sink at night to CO2 source during the day, and partitioned canopy fluxes (FA,EC ) showed a characteristic four-phase CO2 exchange pattern. Results were cross-validated against diel changes in titratable acidity, leaf-unfurling rates, energy exchange fluxes and reported biomass yields. Projected carbon balance (g C m(-2)  year(-1) , mean ± 95% confidence interval) indicated the site was a net sink of -333 ± 24, of which contributions from soil respiration were +692 ± 7, and FA,EC was -1025 ± 25. EC estimated biomass yield was 20.1 Mg (dry) ha(-1)  year(-1) . Average integrated daily FA,EC was -234 ± 5 mmol CO2  m(-2)  d(-1) and persisted almost unchanged after 70 d of drought conditions. Regression analyses were performed on the EC data to identify the best environmental predictors of FA . Results suggest that the carbon acquisition strategy of Agave offers productivity and drought resilience advantages over conventional semi-arid C3 and C4 bioenergy candidates.

  10. A Preliminary Study of Crassulacean Acid Metabolism (CAM) in the Endangered Aquatic Quillwort Isoetes sinensis Palmer in China

    Institute of Scientific and Technical Information of China (English)

    Pang Xin-an; Wang Qing-feng; Gituru W.Robert; Liu Hong; Yang Xiao-lin; Liu Xing

    2003-01-01

    Isoetes sinensis Palmer (Isoetaceae) is an aquatic or amphibious plant that is critically endangered in China. Previous studies have revealed the crassulacean acid metabolism (CAM)-like photosynthetic pathway occurs com-monly in submerged leaves in genus Isoetes. Water chemistry parameters and the titratable acidity content of the plant extract were measured from samples obtained in the early morning (7:00) and late afternoon (15:00) from two I.sinensis populations in China. One population occurs in the eulittoral zone of a freshwater tidal river at low elevation (134 m) and another occurs in a densely vegetated, high elevation (1 100 m) alpine shallow pool. Significant differences in pH and titratable acidity of the plant extract were detected between the morning and afternoon samples. These changes are associated with diurnalchanges in water chemistry. Our results provide the first evidence for the exist-ence of the CAM pathwa in the East Asian endemic Isoetes sinensis Palmer.The magnitude of fluctuations in the titratable acidity of the plant extract mayb e correlated with the severe carbon limitation imposed on the plants by its aquatic habitat.

  11. Crassulacean acid metabolism (CAM) in leaves of Aloe arborescens mill : Comparative studies of the carbon metabolism of chlorenchym and central hydrenchym.

    Science.gov (United States)

    Kluge, M; Knapp, I; Kramer, D; Schwerdtner, I; Ritter, H

    1979-01-01

    In the succulent leaves of Aloe arborescens Mill diurnal oscillations of the malic acid content, being indicative of Crassulacean Acid Metabolism (CAM), were exhibited only by the green mesophyll. In contrast, the malic acid level of the central chloroplast-free water-storing tissue remained constant throughout the day-night cycle. Apart from malate, the green tissue contained high amounts of isocitrat which was lacking in the water tissue. There was no significant transfer from the green mesophyll to the water tissue of (14)C fixed originally via dark (14)CO2 fixation in the mesophyll. Both isolated mesophyll and water tissue were capable of dark CO2 fixation yielding mainly malate as the first stable product. Both tissues have phosphoenolpyruvate carboxylase. However, the enzymes derived from the both sources could be distinguished by their molecular weights and by their kinetic properties, suggesting different phosphoenolpyruvate carboxylase proteins. The conclusion drawn from the experiments is that in a. arborescens the CAM cycle proceeds exclusively in the green mesophyll and that the water tissue, though capable of malate synthesis via β-carboxylation of phosphoenolpyruvate, behaves as an independent metabolic system where CAM is lacking. This view is supported by the finding that the cell walls bordering the green mesophyll from the water tissue lack plasmodesmata, hence conveniant pathways of metabolite transport. PMID:24317763

  12. Amino Acid Metabolism Disorders

    Science.gov (United States)

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  13. Evaluating rare amino acid substitutions (RGC_CAMs in a yeast model clade.

    Directory of Open Access Journals (Sweden)

    Kenneth Polzin

    Full Text Available When inferring phylogenetic relationships, not all sites in a sequence alignment are equally informative. One recently proposed approach that takes advantage of this inequality relies on sites that contain amino acids whose replacement requires multiple substitutions. Identifying these so-called RGC_CAM substitutions (after Rare Genomic Changes as Conserved Amino acids-Multiple substitutions requires that, first, at any given site in the amino acid sequence alignment, there must be a minimum of two different amino acids; second, each amino acid must be present in at least two taxa; and third, the amino acids must require a minimum of two nucleotide substitutions to replace each other. Although theory suggests that RGC_CAM substitutions are expected to be rare and less likely to be homoplastic, the informativeness of RGC_CAM substitutions has not been extensively evaluated in biological data sets. We investigated the quality of RGC_CAM substitutions by examining their degree of homoplasy and internode certainty in nearly 2.7 million aligned amino acid sites from 5,261 proteins from five species belonging to the yeast Saccharomyces sensu stricto clade whose phylogeny is well-established. We identified 2,647 sites containing RGC_CAM substitutions, a number that contrasts sharply with the 100,887 sites containing RGC_non-CAM substitutions (i.e., changes between amino acids that require only a single nucleotide substitution. We found that RGC_CAM substitutions had significantly lower homoplasy than RGC_non-CAM ones; specifically RGC_CAM substitutions showed a per-site average homoplasy index of 0.100, whereas RGC_non-CAM substitutions had a homoplasy index of 0.215. Internode certainty values were also higher for sites containing RGC_CAM substitutions than for RGC_non-CAM ones. These results suggest that RGC_CAM substitutions possess a strong phylogenetic signal and are useful markers for phylogenetic inference despite their rarity.

  14. Nucleic acid encoding DS-CAM proteins and products related thereto

    Energy Technology Data Exchange (ETDEWEB)

    Korenberg, Julie R.

    2005-11-01

    In accordance with the present invention, there are provided Down Syndrome-Cell Adhesion Molecule (DS-CAM) proteins. Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention DS-CAM proteins can be employed in a variety of ways, for example, for the production of anti-DS-CAM antibodies thereto, in therapeutic compositions and methods employing such proteins and/or antibodies. DS-CAM proteins are also useful in bioassays to identify agonists and antagonists thereto.

  15. Benign synthesis of 2-ethylhexanoic acid by cytochrome P450cam: enzymatic, crystallographic, and theoretical studies.

    Science.gov (United States)

    French, K J; Strickler, M D; Rock, D A; Rock, D A; Bennett, G A; Wahlstrom, J L; Goldstein, B M; Jones, J P

    2001-08-14

    This study examines the ability of P450cam to catalyze the formation of 2-ethylhexanoic acid from 2-ethylhexanol relative to its activity on the natural substrate camphor. As is the case for camphor, the P450cam exhibits stereoselectivity for binding (R)- and (S)-2-ethylhexanol. Kinetic studies indicate (R)-2-ethylhexanoic acid is produced 3.5 times as fast as the (S)-enantiomer. In a racemic mixture of 2-ethylhexanol, P450cam produces 50% more (R)-2-ethylhexanoic acid than (S)-2-ethylhexanoic acid. The reason for stereoselective 2-ethylhexanoic acid production is seen in regioselectivity assays, where (R)-2-ethylhexanoic acid comprises 50% of total products while (S)-2-ethylhexanoic acid comprises only 13%. (R)- and (S)-2-ethylhexanol exhibit similar characteristics with respect to the amount of oxygen and reducing equivalents consumed, however, with (S)-2-ethylhexanol turnover producing more water than the (R)-enantiomer. Crystallographic studies of P450cam with (R)- or (S)-2-ethylhexanoic acid suggest that the (R)-enantiomer binds in a more ordered state. These results indicate that wild-type P450cam displays stereoselectivity toward 2-ethylhexanoic acid synthesis, providing a platform for rational active site design. PMID:11583152

  16. Reversible Burst of Transcriptional Changes during Induction of Crassulacean Acid Metabolism in Talinum triangulare.

    Science.gov (United States)

    Brilhaus, Dominik; Bräutigam, Andrea; Mettler-Altmann, Tabea; Winter, Klaus; Weber, Andreas P M

    2016-01-01

    Drought tolerance is a key factor for agriculture in the 21st century as it is a major determinant of plant survival in natural ecosystems as well as crop productivity. Plants have evolved a range of mechanisms to cope with drought, including a specialized type of photosynthesis termed Crassulacean acid metabolism (CAM). CAM is associated with stomatal closure during the day as atmospheric CO2 is assimilated primarily during the night, thus reducing transpirational water loss. The tropical herbaceous perennial species Talinum triangulare is capable of transitioning, in a facultative, reversible manner, from C3 photosynthesis to weakly expressed CAM in response to drought stress. The transcriptional regulation of this transition has been studied. Combining mRNA-Seq with targeted metabolite measurements, we found highly elevated levels of CAM-cycle enzyme transcripts and their metabolic products in T. triangulare leaves upon water deprivation. The carbohydrate metabolism is rewired to reduce the use of reserves for growth to support the CAM-cycle and the synthesis of compatible solutes. This large-scale expression dataset of drought-induced CAM demonstrates transcriptional regulation of the C3-CAM transition. We identified candidate transcription factors to mediate this photosynthetic plasticity, which may contribute in the future to the design of more drought-tolerant crops via engineered CAM. PMID:26530316

  17. Reversible Burst of Transcriptional Changes during Induction of Crassulacean Acid Metabolism in Talinum triangulare1[OPEN

    Science.gov (United States)

    Winter, Klaus

    2016-01-01

    Drought tolerance is a key factor for agriculture in the 21st century as it is a major determinant of plant survival in natural ecosystems as well as crop productivity. Plants have evolved a range of mechanisms to cope with drought, including a specialized type of photosynthesis termed Crassulacean acid metabolism (CAM). CAM is associated with stomatal closure during the day as atmospheric CO2 is assimilated primarily during the night, thus reducing transpirational water loss. The tropical herbaceous perennial species Talinum triangulare is capable of transitioning, in a facultative, reversible manner, from C3 photosynthesis to weakly expressed CAM in response to drought stress. The transcriptional regulation of this transition has been studied. Combining mRNA-Seq with targeted metabolite measurements, we found highly elevated levels of CAM-cycle enzyme transcripts and their metabolic products in T. triangulare leaves upon water deprivation. The carbohydrate metabolism is rewired to reduce the use of reserves for growth to support the CAM-cycle and the synthesis of compatible solutes. This large-scale expression dataset of drought-induced CAM demonstrates transcriptional regulation of the C3–CAM transition. We identified candidate transcription factors to mediate this photosynthetic plasticity, which may contribute in the future to the design of more drought-tolerant crops via engineered CAM. PMID:26530316

  18. Analysis and Simulation of Circadian Multi-Oscillator Systems in a Crassulacean Acid Metabolism Plant

    OpenAIRE

    Bohn, Andreas

    2003-01-01

    Crassulacean acid metabolism (CAM) is an adaptation of photosynthetic organisms to drought stress: improved water-use efficiency is achieved by an optimized temporal arrangement of photosynthetic subprocesses, which are driven by an endogenous pacemaker, i.e. a circadian clock. The present work deals with the hypothesis that the circadian rhythm of gas-exchange of entire leaves of the CAM plant Kalanchoë daigremontiana has to be understood as the collective signal of the population of cells i...

  19. Diurnal variations in leaf fluorescence induction kinetics: variable fluorescence in crassulacean Acid metabolism plants.

    Science.gov (United States)

    Everson, G; Chen, S S; Black, C C

    1983-06-01

    The variable fluorescence of leaves from Kalanchoë daigremontiana and pineapple, Ananas comosus, both CAM plants, was found to change over a 24-hour cycle and to exhibit high temperature-dependent maxima during the night period. The time course of the induced fluorescence was correlated with malic acid accumulation but not with other aspects of CAM such as with the nature of the decarboxylation pathway or with stomatal movements. The variable fluorescences of sunflower (Helianthus annuus L.) and corn (Zea mays L.) leaves were compared with the CAM plants diurnally; both plants also exhibit high fluorescence maxima during the night period. We conclude that the assembly of the photosystems in the light is a primary process in photosynthesis induction and may be influenced by other cellular metabolic processes, specifically in the case of CAM leaves by malic acid accumulation. PMID:16663024

  20. Crassulacean acid metabolism enhances underwater photosynthesis and diminishes photorespiration in the aquatic plant Isoetes australis

    DEFF Research Database (Denmark)

    Pedersen, Ole; Rich, S.M.; Pulido Pérez, Cristina;

    2011-01-01

    Underwater photosynthesis by aquatic plants is often limited by low availability of CO2, and photorespiration can be high. Some aquatic plants utilize crassulacean acid metabolism (CAM) photosynthesis. The benefits of CAM for increased underwater photosynthesis and suppression of photorespiration...... were evaluated for Isoetes australis, a submerged plant that inhabits shallow temporary rock pools. • Leaves high or low in malate were evaluated for underwater net photosynthesis and apparent photorespiration at a range of CO2 and O2 concentrations. • CAM activity was indicated by 9.7-fold higher leaf...... malate at dawn, compared with at dusk, and also by changes in the titratable acidity (lmol H+ equivalents) of leaves. Leaves high in malate showed not only higher underwater net photosynthesis at low external CO2 concentrations but also lower apparent photorespiration. Suppression by CAM of apparent...

  1. Effects of Complementary and Alternative Medicines (CAM) on the Metabolism and Transport of Anticancer Drugs

    NARCIS (Netherlands)

    Mooiman, K.D.

    2013-01-01

    The use of complementary and alternative medicines (CAM), such as herbs and dietary supplements, has become more popular among cancer patients. Cancer patients use these supplements for different reasons such as reduction of side effects and improvement of their quality of life. In general, the use

  2. Contribution of carbon fixed by Rubisco and PEPC to phloem export in the Crassulacean acid metabolism plant Kalanchoë daigremontiana

    OpenAIRE

    Wild, Birgit; Wanek, Wolfgang; Postl, Wolfgang; Richter, Andreas

    2010-01-01

    Crassulacean acid metabolism (CAM) plants exhibit a complex interplay between CO2 fixation by phosphoenolpyruvate carboxylase (PEPC) and ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco), and carbon demand for CAM maintenance and growth. This study investigated the flux of carbon from PEPC and direct Rubisco fixation to different leaf carbon pools and to phloem sap over the diurnal cycle. Concentrations and carbon isotope compositions of starch, soluble sugars, and organic acids were ...

  3. Aspects of CO_2 Uptake in the Crassulacean Acid Metabolism Orchid Phalaenopsis

    OpenAIRE

    Ichihashi, S.; Higuchi, T.; Shibayama, H; Tesima, Y.; Nishiwaki, K; Ota, K.

    2008-01-01

    Phalaenopsis and its hybrids are the most important orchid pot plant commercially in the world now. Research on photosynthesis gives us practical and useful information for improving cultivation. Although conventional gas-exchange technique has some limitations in the research of a crassulacean acid metabolism plant (CAM), we investigated CO_2 uptake in Phalaenopsis. CO_2 uptake at night (Phase 1) changed with temperature. Maximum CO_2 uptake was observed around 20℃. CO_2 absorption at night ...

  4. Day-to-night variations of cytoplasmic pH in a crassulacean acid metabolism plant.

    Science.gov (United States)

    Hafke, J B; Neff, R; Hütt, M T; Lüttge, U; Thiel, G

    2001-01-01

    In crassulacean acid metabolism (CAM) large amounts of malic acid are redistributed between vacuole and cytoplasm in the course of night-to-day transitions. The corresponding changes of the cytoplasmic pH (pHcyt) were monitored in mesophyll protoplasts from the CAM plant Kalanchoe daigremontiana Hamet et Perrier by ratiometric fluorimetry with the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(and-6-)carboxyfluorescein as a pHcyt indicator. At the beginning of the light phase, pHcyt was slightly alkaline (about 7.5). It dropped during midday by about 0.3 pH units before recovering again in the late-day-to-early-dark phase. In the physiological context the variation in pHcyt may be a component of CAM regulation. Due to its pH sensitivity, phosphoenolpyruvate carboxylase appears as a likely target enzyme. From monitoring delta pHcyt in response to loading the cytoplasm with the weak acid salt K-acetate a cytoplasmic H(+)-buffer capacity in the order of 65 mM H+ per pH unit was estimated at a pHcyt of about 7.5. With this value, an acid load of the cytoplasm by about 10 mM malic acid can be estimated as the cause of the observed drop in pHcyt. A diurnal oscillation in pHcyt and a quantitatively similar cytoplasmic malic acid is predicted from an established mathematical model which allows simulation of the CAM dynamics. The similarity of model predictions and experimental data supports the view put forward in this model that a phase transition of the tonoplast is an essential functional element in CAM dynamics. PMID:11732184

  5. Crassulacean Acid Metabolism Permutation and Survival of Caralluma Species (Apocynaceae in Arid Habitats

    Directory of Open Access Journals (Sweden)

    Yahya S. Masrahi

    2012-07-01

    Full Text Available Several species of the stem succulent Caralluma (Apocynaceae are abundant perennials in arid regions of the Arabian Peninsula. These arid regions have a short wet season with erratic rainfall and are characterized by harsh climatic conditions of high temperature, high evaporation and sand storms. Work presented in this paper aimed at investigating importance of Crassulacean Acid Metabolism (CAM for survival of three Caralluma species in their natural habitat. Investigations involved studying stomatal characteristics, stomatal diffusive conductance, chlorophyll fluorescence, and CAM in three species of Caralluma, namely C. acutangula (Decne. N.E.Br., C. edulis (Edgew. Benth. ex Hook.f., and C. subulata (Forssk. Decne. Microscopic examination revealed a pattern of stomatal characteristics typical of CAM plants in these three Caralluma species. Results showed that these three Caralluma species were obligate CAM plants exhibiting this mode of photosynthesis during both the wet and the dry seasons. Under protracted water stress during the long dry season very low values of stomatal diffusive conductance and dampening of CAM acidification-deacidification cycles denoted the tendency of these three Caralluma species to shift from the obligate CAM physiotype to CAM-idling mode. Chlorophyll fluorescence measurements indicated that protracted water stress induced a reduction in Photosystem II (PSII antenna efficiency and quantum yield in the three studied Caralluma species. This reduction of PSII activity occurred in concomitance with a marked rise in non-photochemical quenching of chlorophyll fluorescence denoting operation of non-photochemical energy dissipating mechanisms known to be important for photoprotection of the photosynthetic apparatus.

  6. Mitochondrial respiration in ME-CAM, PEPCK-CAM, and C₃ succulents: comparative operation of the cytochrome, alternative, and rotenone-resistant pathways.

    Science.gov (United States)

    Peckmann, Klaus; von Willert, Dieter J; Martin, Craig E; Herppich, Werner B

    2012-05-01

    Mitochondria are important in the function and control of Crassulacean acid metabolism (CAM) during organic acid accumulation at night and acid decarboxylation in the day. In plants of the malic enzyme-(ME) type and the phosphoenolpyruvate carboxykinase- (PEPCK) type, mitochondria may exert their role in the control of the diurnal rhythm of malic and citric acids to a differential degree. In plants of both CAM types, the oxidative capacity of mitochondria, as well as the activity of CAM-linked mitochondrial enzymes, and of the alternative and the rotenone-resistant pathways of substrate oxidation were compared. Furthermore, a C₃ succulent was included, as well as both C₃ and CAM forms of Mesembryanthemum crystallinum during a salt-induced C₃-to-CAM shift. Mitochondria of PEPCK-type CAM plants exhibited a lower activity of malate oxidation, ratio of malate to succinate oxidation, and activity of mitochondrial NAD-ME. With the exception of Kalanchoë daigremontiana, leaf mitochondria of all other CAM species were highly sensitive to cyanide (80-100%), irrespective of the oxidant used. This indicates that the alternative oxidase is not of general importance in CAM. By contrast, rotenone-insensitive substrate oxidation was very high (50-90%) in all CAM species. This is the first comparison of the rotenone-insensitive pathway of respiration in plants with different CAM-types. The results of this study confirm that mitochondria are involved in the control of CAM to different degrees in the two CAM types, and they highlight the multiple roles of mitochondria in CAM.

  7. CAM Photosynthesis in Submerged Aquatic Plants

    Science.gov (United States)

    Keeley, J.E.

    1998-01-01

    Crassulacean acid metabolism (CAM) is a CO2-concentrating mechanism selected in response to aridity in terrestrial habitats, and, in aquatic environments, to ambient limitations of carbon. Evidence is reviewed for its presence in five genera of aquatic vascular plants, including Isoe??tes, Sagittaria, Vallisneria, Crassula, and Littorella. Initially, aquatic CAM was considered by some to be an oxymoron, but some aquatic species have been studied in sufficient detail to say definitively that they possess CAM photosynthesis. CO2-concentrating mechanisms in photosynthetic organs require a barrier to leakage; e.g., terrestrial C4 plants have suberized bundle sheath cells and terrestrial CAM plants high stomatal resistance. In aquatic CAM plants the primary barrier to CO2 leakage is the extremely high diffusional resistance of water. This, coupled with the sink provided by extensive intercellular gas space, generates daytime CO2(Pi) comparable to terrestrial CAM plants. CAM contributes to the carbon budget by both net carbon gain and carbon recycling, and the magnitude of each is environmentally influenced. Aquatic CAM plants inhabit sites where photosynthesis is potentially limited by carbon. Many occupy moderately fertile shallow temporary pools that experience extreme diel fluctuations in carbon availability. CAM plants are able to take advantage of elevated nighttime CO2 levels in these habitats. This gives them a competitive advantage over non-CAM species that are carbon starved during the day and an advantage over species that expend energy in membrane transport of bicarbonate. Some aquatic CAM plants are distributed in highly infertile lakes, where extreme carbon limitation and light are important selective factors. Compilation of reports on diel changes in titratable acidity and malate show 69 out of 180 species have significant overnight accumulation, although evidence is presented discounting CAM in some. It is concluded that similar proportions of the aquatic

  8. Regional myocardial free fatty acid metabolism

    International Nuclear Information System (INIS)

    Experimental evidence to date has confirmed the potential value of radioactive labelled free fatty acid (FFA) and their analogs for the assessment of regional myocardial FFA metabolism despite a number of current limitations. It is emphasized that with these agents only one specific aspect of myocardial metabolism, that of FFA, can be tested and that with these compounds information on the overall metabolic state cannot always be obtained. (WU)

  9. 2-Hydroxy Acids in Plant Metabolism

    OpenAIRE

    Maurino, Veronica G.; Engqvist, Martin K. M.

    2015-01-01

    Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in pla...

  10. Capture of Tumor Cells on Anti-EpCAM-Functionalized Poly(acrylic acid)-Coated Surfaces.

    Science.gov (United States)

    Andree, Kiki C; Barradas, Ana M C; Nguyen, Ai T; Mentink, Anouk; Stojanovic, Ivan; Baggerman, Jacob; van Dalum, Joost; van Rijn, Cees J M; Terstappen, Leon W M M

    2016-06-15

    The presence of tumor cells in blood is predictive of short survival in several cancers and their isolation and characterization can guide toward the use of more effective treatments. These circulating tumor cells (CTC) are, however, extremely rare and require a technology that is sufficiently sensitive and specific to identify CTC against a background of billions of blood cells. Immuno-capture of cells expressing the epithelial cell adhesion molecule (EpCAM) are frequently used to enrich CTC from blood. The choice of bio conjugation strategy and antibody clone is crucial for adequate cell capture but is poorly understood. In this study, we determined the binding affinity constants and epitope binding of the EpCAM antibodies VU1D-9, HO-3, EpAb3-5, and MJ-37 by surface plasmon resonance imaging (SPRi). Glass surfaces were coated using a poly(acrylic acid) based coating and functionalized with anti-EpCAM antibodies. Binding of cells from the breast carcinoma cell line (SKBR-3) to the functionalized surfaces were compared. Although EpAb3-5 displayed the highest binding affinity HO-3 captured the highest amount of cells. Hence we report differences in the performance of the different antibodies and more importantly that the choice of antibody to capture CTC should be based on multiple assays. PMID:27187784

  11. METABOLISMO ÁCIDO DE LAS CRASULÁCEAS Crassulacean Acid Metabolism

    Directory of Open Access Journals (Sweden)

    THOMAS DAVID GEYDAN

    Full Text Available Se presenta una revisión del metabolismo ácido de las Crasuláceas, caracterizado por la ocurrencia, actividad y plasticidad del mecanismo desde un punto de vista fisiológico, bioquímico y molecular, enmarcado por la presencia de las denominadas cuatro fases de dicho metabolismo y su repercusión y expresión por diversas restricciones hídricas a nivel ecológico. Se presentan las principales enzimas y metabolitos básicos para el funcionamiento del metabolismo CAM, así como su modo de acción y control celular. Finalmente, se muestra que la plasticidad fenotípica en patrones de expresión CAM se encuentra mediada por condiciones ambientales y por señalizaciones moleculares.A review of Crassulacean acid metabolism is presented, characterized by showing the occurrence, activity and plasticity of these complex mechanism at the physiological, biochemical and molecular level, framed by the presence of the denominated four phases in CAM and its repercussion and expression due to different stresses in an ecological context. The basic enzymes, and metabolites necessary for the optional functioning of CAM are presented as well as their mode of action and cellular control. Finally, it is shown how environmental conditions and molecular signalling mediate the phenotypic plasticity.

  12. Patterns of Carbon Partitioning in Leaves of Crassulacean Acid Metabolism Species during Deacidification.

    Science.gov (United States)

    Christopher, J. T.; Holtum, JAM.

    1996-09-01

    Carbohydrates stored during deacidification in the light were examined in 11 Crassulacean acid metabolism (CAM) species from widely separated taxa grown under uniform conditions. The hypothesis that NAD(P) malic enzyme CAM species store chloroplastic starch and glucans, and phosphoenolpyruvate carboxykinase species store extrachloroplastic sugars or polymers was disproved. Of the six malic enzyme species examined, Kalanchoe tubiflora, Kalanchoe pinnata, Kalanchoe daigremontiana, and Vanilla planifolia stored mainly starch. Sansevieria hahnii stored sucrose and Agave guadalajarana did not store starch, glucose, fructose, or sucrose. Of the five phosphoenolpyruvate carboxykinase species investigated, Ananus comosus stored extrachloroplastic carbohydrate, but Stapelia gigantea, Hoya carnosa, and Portea petropolitana stored starch, whereas Aloe vera stored both starch and glucose. Within families, the major decarboxylase was common for all species examined, whereas storage carbohydrate could differ both between and within genera. In the Bromeliaceae, A. comosus stored mainly fructose, but P. petropolitana stored starch. In the genus Aloe, A. vera stored starch and glucose, but A. arborescens is known to store a galactomannan polymer. We postulate that the observed variation in carbohydrate partitioning between CAM species is the result of two principal components: (a) constraints imposed by the CAM syndrome itself, and (b) diversity in biochemistry resulting from different evolutionary histories. PMID:12226397

  13. Aquatic CAM photosynthesis: a brief history of its discovery

    Science.gov (United States)

    Keeley, Jon E.

    2014-01-01

    Aquatic CAM (Crassulacean Acid Metabolism) photosynthesis was discovered while investigating an unrelated biochemical pathway concerned with anaerobic metabolism. George Bowes was a significant contributor to this project early in its infancy. Not only did he provide me with some valuable perspectives on peer review rejections, but by working with his gas exchange system I was able to take our initial observations of diel fluctuations in malic acid to the next level, showing this aquatic plant exhibited dark CO2 uptake. CAM is universal in all aquatic species of the worldwide Lycophyta genus Isoetes and non-existent in terrestrial Isoetes. Outside of this genus aquatic CAM has a limited occurrence in three other families, including the Crassulaceae. This discovery led to fascinating adventures in the highlands of the Peruvian Andes in search of Stylites, a terrestrial relative of Isoetes. Stylites is a plant that is hermetically sealed from the atmosphere and obtains all of its carbon from terrestrial sources and recycles carbon through CAM. Considering the Mesozoic origin of Isoetes in shallow pools, coupled with the fact that aquatic Isoetes universally possess CAM, suggests the earliest evolution of CAM photosynthesis was most likely not in terrestrial plants.

  14. Metabolism of sinapic acid and related compounds in the rat.

    Science.gov (United States)

    Griffiths, L A

    1969-07-01

    1. Administration of sinapic acid to the rat results in the excretion of 3-hydroxy-5-methoxyphenylpropionic acid, dihydrosinapic acid, 3-hydroxy-5-methoxycinnamic acid and unchanged sinapic acid in the urine. The sinapic acid conjugate sinalbin is also catabolized to free sinapic acid and 3-hydroxy-5-methoxyphenylpropionic acid in the rat. 2. 3,4,5-Trimethoxycinnamic acid is metabolized in part to sinapic acid and 3-hydroxy-5-methoxyphenylpropionic acid. 3. 3,5-Dimethoxycinnamic acid is metabolized to 3-hydroxy-5-methoxycinnamic acid and 3-hydroxy-5-methoxyphenylpropionic acid. 4. The metabolic interrelationships of these compounds were studied by the administration of intermediates and a metabolic pathway is proposed. 5. The metabolism of the corresponding benzoic acids was studied, but these compounds and their metabolites were shown not to be intermediates or products of the metabolism of the related cinnamic acids. PMID:5386182

  15. The pineapple genome and the evolution of CAM photosynthesis

    Science.gov (United States)

    Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 ...

  16. Bonding effectiveness of self-adhesive and conventional-type adhesive resin cements to CAD/CAM resin blocks. Part 2: Effect of ultrasonic and acid cleaning.

    Science.gov (United States)

    Kawaguchi, Asuka; Matsumoto, Mariko; Higashi, Mami; Miura, Jiro; Minamino, Takuya; Kabetani, Tomoshige; Takeshige, Fumio; Mine, Atsushi; Yatani, Hirofumi

    2016-01-01

    The present study assessed the effect of ultrasonic and acid cleaning on resin cement bonding to CAD/CAM resin blocks. One of two resin cements, PANAVIA V5 (PV5) or PANAVIA SA CEMENT HANDMIX (PSA), were bonded to one of 24 CAD/CAM blocks (KATANA AVENCIA BLOCK). Each cement group was divided into four subgroups: no cleaning (Ctl), ultrasonic cleaning (Uc), acid cleaning (Ac) and Uc+Ac. Micro-tensile bond strengths (µTBSs) were measured immediately and 1, 3, and 6 months after water storage. Block surfaces after each treatment were analyzed by scanning electron microscopy. Analysis of variance revealed a statistically significant effect for the parameters 'surface treatment' (psandblasting was effective in removing residual alumina particles, it did not affect the long-term bonding durability with non-contaminated CAD/CAM resin blocks. PMID:26830822

  17. On the Mechanism of Reinitiation of Endogenous Crassulacean Acid Metabolism Rhythm by Temperature Changes.

    Science.gov (United States)

    Grams, TEE.; Borland, A. M.; Roberts, A.; Griffiths, H.; Beck, F.; Luttge, U.

    1997-04-01

    Under continuous light the endogenous Crassulacean acid metabolism (CAM) rhythm of Kalanchoe daigremontiana Hamet et Perrier de la Bathie disappears at high (>29.0[deg]C) or low (<8.0[deg]C) temperatures. We investigated the reinitiation of rhythmicity when temperature was reduced from above the upper and increased from below the lower threshold level via measurements of (a) short-term changes in carbon-isotope discrimination to illustrate shifts between C3 and C4 carboxylation in vivo, and (b) the malate sensitivity of phosphoenolpyruvate carboxylase (PEPC) in vitro. When the net CO2-exchange rhythm disappears at both temperatures, the instantaneous discrimination indicates low PEPC activity. Leaf malate concentration and osmolarity attain high and low values at low and high temperatures, respectively. After small temperature increases or reductions from the low and high temperatures, respectively, the rhythm is reinitiated, with phases shifted by 180[deg] relative to each other. This can be related to the contrasting low and high leaf malate concentrations due to direct inhibition of PEPC and possibly also of the phosphorylation of PEPC by malate. The experimental results were satisfactorily simulated by a mathematical CAM-cycle model, with temperature acting only on the passive efflux of malate from the vacuole. We stress the important role of the tonoplast in malate compartmentation and of malate itself for the reinitiation and generation of endogenous CAM rhythmicity. PMID:12223675

  18. Linking uric acid metabolism to diabetic complications

    Institute of Scientific and Technical Information of China (English)

    Akifumi; Kushiyama; Kentaro; Tanaka; Shigeko; Hara; Shoji; Kawazu

    2014-01-01

    Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

  19. Lateral diffusion of CO2 in leaves of the crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perrier.

    Science.gov (United States)

    Duarte, Heitor M; Jakovljevic, Ivona; Kaiser, Friedemann; Lüttge, Ulrich

    2005-04-01

    Dynamic patchiness of photosystem II (PSII) activity in leaves of the crassulacean acid metabolism (CAM) plant Kalanchoe daigremontiana Hamet et Perrier, which was independent of stomatal control and was observed during both the day/night cycle and circadian endogenous oscillations of CAM, was previously explained by lateral CO2 diffusion and CO2 signalling in the leaves [Rascher et al. (2001) Proc Natl Acad Sci USA 98:11801-11805; Rascher and Luttge (2002) Plant Biol 4:671-681]. The aim here was to actually demonstrate the importance of lateral CO2 diffusion and its effects on localized PSII activity. Covering small sections of entire leaves with silicone grease was used for local exclusion of a contribution of atmospheric CO2 to internal CO2 via transport through stomata. A setup for combined measurement of gas exchange and chlorophyll fluorescence imaging was used for recording photosynthetic activity with a spatiotemporal resolution. When remobilization of malic acid from vacuolar storage and its decarboxylation in the CAM cycle caused increasing internal CO2 concentrations sustaining high PSII activity behind closed stomata, PSII activity was also increased in adjacent leaf sections where vacuolar malic acid accumulation was minimal as a result of preventing external CO2 supply due to leaf-surface greasing, and where therefore CO2 could only be supplied by diffusion from the neighbouring malic acid-remobilizing leaf tissue. This demonstrates lateral CO2 diffusion and its effect on local photosynthetic activity. PMID:15843962

  20. Stomatal responses to CO2 during a diel Crassulacean acid metabolism cycle in Kalanchoe daigremontiana and Kalanchoe pinnata.

    Science.gov (United States)

    von Caemmerer, Susanne; Griffiths, Howard

    2009-05-01

    To investigate the diurnal variation of stomatal sensitivity to CO2, stomatal response to a 30 min pulse of low CO2 was measured four times during a 24 h time-course in two Crassulacean acid metabolism (CAM) species Kalanchoe daigremontiana and Kalanchoe pinnata, which vary in the degree of succulence, and hence, expression and commitment to CAM. In both species, stomata opened in response to a reduction in pCO2 in the dark and in the latter half of the light period, and thus in CAM species, chloroplast photosynthesis is not required for the stomatal response to low pCO2. Stomata did not respond to a decreased pCO2 in K. daigremontiana in the light when stomata were closed, even when the supply of internal CO2 was experimentally reduced. We conclude that stomatal closure during phase III is not solely mediated by high internal pCO2, and suggest that in CAM species the diurnal variability in the responsiveness of stomata to pCO2 could be explained by hypothesizing the existence of a single CO2 sensor which interacts with other signalling pathways. When not perturbed by low pCO2, CO2 assimilation rate and stomatal conductance were correlated both in the light and in the dark in both species. PMID:19210641

  1. Separation and purification of the tonoplast ATPase and pyrophosphatase from plants with constitutive and inducible Crassulacean acid metabolism.

    Science.gov (United States)

    Bremberger, C; Haschke, H P; Lüttge, U

    1988-10-01

    Tonoplast vesicles were isolated from Kalanchoe daigremontiana Hamet et Pierrer de la Bâthie and Mesembryanthemum crystallinum L., exhibiting constitutive and inducible crassulacean acid metabolism (CAM), respectively. Membrane-bound proteins were detergent-solubilized with 2% of Triton X-100. During CAM induction in M. crystallinum, ATPase activity increases four-fold, whereas pyrophosphatase activity decreases somewhat. With all plants, ATPase and pyrophosphatase could be separated by size-exclusion chromatography (SEC, Sephacryl S 400), and the ATPase was further purified by diethylaminoethyl-ion-exchange chromatography. Sodium-dodecyl-sulfate electrophoresis of the SEC fractions from K. daigremontiana containing maximum ATPase activity separates several protein bands, indicating subunits of 72, 56, 48, 42, 28, and 16 kDa. Purified ATPase from M. crystallinum in the C3 and CAM states shows a somewhat different protein pattern. With M. crystallinum, an increase in ATP-hydrolysis and changes in the subunit composition of the native enzyme indicate that the change from the C3 to the CAM state is accompanied by de-novo synthesis and by structural changes of the tonoplast ATPase. PMID:24221927

  2. Leaf anatomy and ultrastructure of the Crassulacean-acid-metabolism plant Kalanchoe daigremontiana.

    Science.gov (United States)

    Balsamo, R A; Uribe, E G

    1988-02-01

    Light-microscopic analysis of leaf clearings of the obligate Crassulacean-acid-metabolism (CAM) species Kalanchoe daigremontiana Hamet et Perr. has shown the existence of unusual and highly irregular venation patterns. Fifth-order veins exhibit a three-dimensional random orientation with respect to the mesophyll. Minor veins were often observed crossing over or under each other and over and under major veins in the mesophyll. Paraffin sections of mature leaves show tannin cells scattered throughout the mesophyll rather evenly spaced, and a distinct layer of tannin cells below the abaxial epidermis. Scanning electron microscopy showed that bundle-sheath cells are distinct from the surrounding mesophyll in veins of all orders. Transmission electron microscopy demonstrated developing sieve-tube elements in expanded leaves. Cytosolic vesicles produced by dictyosomes undergo a diurnal variation in number and were often observed in association with the chloroplasts. These vesicles are an interesting feature of cell ultrastructure of CAM cells and may serve a regulatory role in the diurnal malic-acid fluctuations in this species. PMID:24226398

  3. Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells

    Directory of Open Access Journals (Sweden)

    Sebastian Werneburg

    2015-05-01

    Full Text Available Oligodendrocyte precursor cells (OPCs are the progenitors of myelinating oligodendrocytes in brain development and repair. Successful myelination depends on the control of adhesiveness during OPC migration and axon contact formation. The decoration of cell surface proteins with the glycan polysialic acid (polySia is a key regulatory element of OPC interactions during development and under pathological conditions. By far the major protein carrier of polySia is the neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain. In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a heterogeneous precursor cell population, which is the primary source for oligodendrocytes in development and myelin repair but can also give rise to astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is expressed by OPCs and its occurrence in humans is elusive. By generating uniform human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is present on human OPCs but down-regulated during differentiation into myelin basic protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM-180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human OPCs.

  4. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However....... However, this does not seem applicable for inflammatory diseases or human models of sepsis, in which the enhanced imbalance between these two processes is observed within an enhanced, normal or reduced muscle protein turnover.......PURPOSE OF REVIEW: This review highlights the role of cytokines, in particular tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in relation to the nature of human in-vivo muscle wasting in disease. RECENT FINDINGS: Infusion of human TNF-α and IL-6 in healthy individuals, acutely...

  5. What is the potential for dark CO2 fixation in the facultative crassulacean acid metabolism species Talinum triangulare?

    Science.gov (United States)

    Herrera, Ana; Ballestrini, Caín; Montes, Enrique

    2015-02-01

    In obligate Crassulacean acid metabolism (CAM) plants, dark CO2 fixation is almost the sole route of CO2 fixation and, under drought, continues for long periods. In contrast, in plants of the facultative CAM species Talinum triangulare under experimental drought, dark CO2 fixation provides a small proportion of the daily assimilation observed in watered plants and occurs only for a few days, after which almost nil CO2 fixation is observed. Under field conditions, with a practically unlimited substrate volume, drought-induced CAM might operate for a longer period and make a higher contribution to daily CO2 fixation. Greenhouse-grown plants of T. triangulare were subjected to low and nearly constant soil water content; the operation of CAM was assessed through the measurement of nocturnal proton accumulation and dark CO2 fixation. Dark CO2 fixation appeared 19d after the onset of drought; its contribution during three months of experiment to daily CO2 assimilation ranged from 0.5 to 30.7% with a mean of 13.5%. Twenty days after the beginning of treatment, nocturnal proton accumulation increased six times and remained high for over three months. In spite of low soil water content, leaves did not engage in dark CO2 fixation all the time but dark CO2 fixation was large enough to produce an increase in relative (13)C composition of mature leaves compared to watered plants but not to the value in short-term drought experiments. Leaf anatomical characteristics may guarantee the achievement of higher rates of dark CO2 fixation but results evidence the occurrence of a limit to the expression of CAM that remains to be determined. PMID:25462967

  6. Fe3O4/Salicylic acid nanoparticles behavior on chick CAM vasculature

    International Nuclear Information System (INIS)

    A modified ferrite co-precipitation synthesis was used to obtain core–shell Fe3O4/salicylic acid magnetic nanoparticles (Sa-MNP) with well-dispersed aqueous solution properties. The newly developed iron oxide nanoparticles properties were investigated with X-ray diffraction, Fourier transform infrared spectrometry, transmission electron microscopy, and laser light scattering for their characteristic establishment. The resulting Sa-MNPs have spherical morphology, homogenous size distribution around 60 nm (35 nm FWHM), and a 67 mV Zeta potential value (15.5 mV STDV). In vivo biocompatibility and intravascular behavior of the 60 nm diameter size range synthesized nanoparticles were evaluated on chick chorioallantoic membrane model. The results show a reversible and good controlled intravascular accumulation under static magnetic field, a low risk of embolisation with nanoparticle aggregates detached from venous intravascular nanoblocked areas, a persistent blocking of the arterioles and dependent capillaries network, a good circulating life time and biocompatibility. The beneficial effects of salicylic acid (SA) and in vivo demonstrated capacity of Sa-MNPs to cutoff regional vascular supply under static magnetic field control suggest a possible biomedical application of these MNPs in targeted cancer therapy through magnetic controlled blood flow nanoblocking mechanism

  7. Fe{sub 3}O{sub 4}/Salicylic acid nanoparticles behavior on chick CAM vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Mihaiescu, Dan Eduard [' Politechnica' University of Bucharest, Faculty of Applied Chemistry and Materials Science (Romania); Buteica, Alice Sandra; Neamtu, Johny [University of Medicine and Pharmacy of Craiova, Faculty of Pharmacy (Romania); Istrati, Daniela [' Politechnica' University of Bucharest, Faculty of Applied Chemistry and Materials Science (Romania); Mindrila, Ion, E-mail: tutu0101@yahoo.com [University of Medicine and Pharmacy of Craiova, Department of Morphological Sciences (Romania)

    2013-08-15

    A modified ferrite co-precipitation synthesis was used to obtain core-shell Fe{sub 3}O{sub 4}/salicylic acid magnetic nanoparticles (Sa-MNP) with well-dispersed aqueous solution properties. The newly developed iron oxide nanoparticles properties were investigated with X-ray diffraction, Fourier transform infrared spectrometry, transmission electron microscopy, and laser light scattering for their characteristic establishment. The resulting Sa-MNPs have spherical morphology, homogenous size distribution around 60 nm (35 nm FWHM), and a 67 mV Zeta potential value (15.5 mV STDV). In vivo biocompatibility and intravascular behavior of the 60 nm diameter size range synthesized nanoparticles were evaluated on chick chorioallantoic membrane model. The results show a reversible and good controlled intravascular accumulation under static magnetic field, a low risk of embolisation with nanoparticle aggregates detached from venous intravascular nanoblocked areas, a persistent blocking of the arterioles and dependent capillaries network, a good circulating life time and biocompatibility. The beneficial effects of salicylic acid (SA) and in vivo demonstrated capacity of Sa-MNPs to cutoff regional vascular supply under static magnetic field control suggest a possible biomedical application of these MNPs in targeted cancer therapy through magnetic controlled blood flow nanoblocking mechanism.

  8. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti;

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  9. Conserved and divergent rhythms of crassulacean acid metabolism-related and core clock gene expression in the cactus Opuntia ficus-indica.

    Science.gov (United States)

    Mallona, Izaskun; Egea-Cortines, Marcos; Weiss, Julia

    2011-08-01

    The cactus Opuntia ficus-indica is a constitutive Crassulacean acid metabolism (CAM) species. Current knowledge of CAM metabolism suggests that the enzyme phosphoenolpyruvate carboxylase kinase (PPCK) is circadian regulated at the transcriptional level, whereas phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK) are posttranslationally controlled. As little transcriptomic data are available from obligate CAM plants, we created an expressed sequence tag database derived from different organs and developmental stages. Sequences were assembled, compared with sequences in the National Center for Biotechnology Information nonredundant database for identification of putative orthologs, and mapped using Kyoto Encyclopedia of Genes and Genomes Orthology and Gene Ontology. We identified genes involved in circadian regulation and CAM metabolism for transcriptomic analysis in plants grown in long days. We identified stable reference genes for quantitative polymerase chain reaction and found that OfiSAND, like its counterpart in Arabidopsis (Arabidopsis thaliana), and OfiTUB are generally appropriate standards for use in the quantification of gene expression in O. ficus-indica. Three kinds of expression profiles were found: transcripts of OfiPPCK oscillated with a 24-h periodicity; transcripts of the light-active OfiNADP-ME and OfiPPDK genes adapted to 12-h cycles, while transcript accumulation patterns of OfiPEPC and OfiMDH were arrhythmic. Expression of the circadian clock gene OfiTOC1, similar to Arabidopsis, oscillated with a 24-h periodicity, peaking at night. Expression of OfiCCA1 and OfiPRR9, unlike in Arabidopsis, adapted best to a 12-h rhythm, suggesting that circadian clock gene interactions differ from those of Arabidopsis. Our results indicate that the evolution of CAM metabolism could be the result of modified circadian regulation at both the transcriptional and posttranscriptional

  10. Discrimination in the dark. Resolving the interplay between metabolic and physical constraints to phosphoenolpyruvate carboxylase activity during the crassulacean acid metabolism cycle.

    Science.gov (United States)

    Griffiths, Howard; Cousins, Asaph B; Badger, Murray R; von Caemmerer, Susanne

    2007-02-01

    A model defining carbon isotope discrimination (delta13C) for crassulacean acid metabolism (CAM) plants was experimentally validated using Kalanchoe daigremontiana. Simultaneous measurements of gas exchange and instantaneous CO2 discrimination (for 13C and 18O) were made from late photoperiod (phase IV of CAM), throughout the dark period (phase I), and into the light (phase II). Measurements of CO2 response curves throughout the dark period revealed changing phosphoenolpyruvate carboxylase (PEPC) capacity. These systematic changes in PEPC capacity were tracked by net CO2 uptake, stomatal conductance, and online delta13C signal; all declined at the start of the dark period, then increased to a maximum 2 h before dawn. Measurements of delta13C were higher than predicted from the ratio of intercellular to external CO2 (p(i)/p(a)) and fractionation associated with CO2 hydration and PEPC carboxylations alone, such that the dark period mesophyll conductance, g(i), was 0.044 mol m(-2) s(-1) bar(-1). A higher estimate of g(i) (0.085 mol m(-2) s(-1) bar(-1)) was needed to account for the modeled and measured delta18O discrimination throughout the dark period. The differences in estimates of g(i) from the two isotope measurements, and an offset of -5.5 per thousand between the 18O content of source and transpired water, suggest spatial variations in either CO2 diffusion path length and/or carbonic anhydrase activity, either within individual cells or across a succulent leaf. Our measurements support the model predictions to show that internal CO2 diffusion limitations within CAM leaves increase delta13C discrimination during nighttime CO2 fixation while reducing delta13C during phase IV. When evaluating the phylogenetic distribution of CAM, carbon isotope composition will reflect these diffusive limitations as well as relative contributions from C3 and C4 biochemistry. PMID:17142488

  11. The Role of Microbial Amino Acid Metabolism in Host Metabolism

    Directory of Open Access Journals (Sweden)

    Evelien P. J. G. Neis

    2015-04-01

    Full Text Available Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.

  12. Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms

    Directory of Open Access Journals (Sweden)

    Johanna M Gostner

    2015-07-01

    Full Text Available Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1-infected patients. Both essential amino acids, tryptophan and phenylalanine are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms such as development of depression, fatigue, and cognitive impairment.Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.

  13. Metabolism of amino acid amides in Pseudomonas putida ATCC 12633

    NARCIS (Netherlands)

    Hermes, H.F.M.; Croes, L.M.; Peeters, W.P.H.; Peters, P.J.H.; Dijkhuizen, L.

    1993-01-01

    The metabolism of the natural amino acid L-valine, the unnatural amino acids D-valine, and D-, L-phenylglycine (D-, L-PG), and the unnatural amino acid amides D-, L-phenylglycine amide (D, L-PG-NH2) and L-valine amide (L-Val-NH2) was studied in Pseudomonas putida ATCC 12633. The organism possessed c

  14. Metabolic strategies of beer spoilage lactic acid bacteria in beer.

    Science.gov (United States)

    Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

    2016-01-01

    Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis.

  15. Metabolic strategies of beer spoilage lactic acid bacteria in beer.

    Science.gov (United States)

    Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

    2016-01-01

    Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis. PMID:26398285

  16. A Preliminary Study of Crassulacean Acid Metabolism (CAM) in the Endangered Aquatic Quillwort Isoetes sinensis Palmer in China

    Institute of Scientific and Technical Information of China (English)

    PangXin-an; WangQing-feng; GituruW.Robert; LiuHong; YangXiao-lin; LiuXing

    2003-01-01

    Isoetes sinensis Palmer (Isoetaceae) is an aquatic or amphibious plant that is critically endangered in China. Previous studies have revealed the crassulacean acid metabolism (CAM)-like photosynthetic pathway occurs commonly in submerged leaves in genus Isoetes. Water chemistry parameters and the titratable acidity content of the plant extract were measured from samples obtained in the early morning (7:00) and late afternoon (15=00) from two I.sinensis populations in China. One population occurs in the eulittoral zone of a freshwater tidal river at low elevation (134 m) and another occurs in a densely vegetated, high elevation (1 100 m) alpine shallow pool. Significant difference sin pH and titratable acidity of the plant extract were detected between the morning and afternoon samples. These changes are associated with diurnal changes in water chemistry. Our results provide the first evidence for the existence of the CAM pathway in the East Asian endemic Isoetes sinensis Palmer.The magnitude of fluctuations in the titratable acidity of the plant extract may be correlated with the severe carbon limitation imposed on the plants by its aquatic habitat.

  17. Metabolism and transport of gamma-carboxyglutamic acid.

    Science.gov (United States)

    Shah, D V; Tews, J K; Harper, A E; Suttie, J W

    1978-03-01

    gamma-Carboxyglutamic acid residues have beeh shown to be present in prothrombin, the other vitamin K-dependent clotting factors, and more recently in bone and kidney proteins. This amino acid is formed by a posttranslational vitamin K-dependent carboxylation of glutamyl residues in polypeptide precursors of these protens. It has now been demonstrated that this amino acid, either in the free or peptide-bound form, is not metabolically degraded by the rat, but is quantitatively excreted in the urine. In nephrectomized rats, the tissue concentration of intravenously administered gamma-carboxyglutamic acid is increased, but there is still no evidence of any oxidative metabolism of this amino acid. These amino acid is transported by kidney slices against a concentration gradient, but does not accumulate in liver, intestinal or brain tissues. Preliminary data suggest that gamma-carboxyglutamic acid may be concentrated by a carrier system different from that utilized by other amino acids. PMID:629998

  18. Citric acid cycle and role of its intermediates in metabolism.

    Science.gov (United States)

    Akram, Muhammad

    2014-04-01

    The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It is the most important metabolic pathway for the energy supply to the body. TCA is the most important central pathway connecting almost all the individual metabolic pathways. In this review article, introduction, regulation and energetics of TCA cycle have been discussed. The present study was carried out to review literature on TCA cycle.

  19. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    Directory of Open Access Journals (Sweden)

    Marko Kreft

    2012-04-01

    Full Text Available Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

  20. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

    NARCIS (Netherlands)

    Lefebvre, Philippe; Cariou, Bertrand; Lien, Fleur; Kuipers, Folkert; Staels, Bart

    2009-01-01

    Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation. Physiol Rev 89: 147-191,2009; doi: 10.1152/physrev.00010.2008. - The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an incre

  1. Natural toxins that affect plant amino acid metabolism

    Science.gov (United States)

    A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

  2. Engineering metabolic highways in Lactococci and other lactic acid bacteria

    NARCIS (Netherlands)

    Vos, de W.M.; Hugenholtz, J.

    2004-01-01

    Lactic acid bacteria (LAB) are widely used in industrial food fermentations and are receiving increased attention for use as cell factories for the production of food and pharmaceutical products. Glycolytic conversion of sugars into lactic acid is the main metabolic highway in these Gram-positive ba

  3. Specific fatty acids as metabolic modulators in the dairy cow

    Directory of Open Access Journals (Sweden)

    J.A.A. Pires

    2008-07-01

    Full Text Available This review summarizes recent developments on the utilization of specific fatty acids to modulate bovine energy metabolism, with emphasis on the periparturient dairy cow. A number of experiments have assessed the effects of polyunsaturated fatty acids on bovine hepatic energy metabolism using in vitro and in vivo models. Treatment of hepatocytes with specific fatty acids altered energy metabolism in vitro. For example, linolenic acid seemed to decrease hepatocyte triacylglycerol accumulation. This effect was confirmed in vivo, using parenteral infusions of emulsions derived from different fat sources to feed-restricted non-lactating cows. Additionally, polyunsaturated fatty acids can increase whole body response to insulin, potentially enhancing antilipolytic effects of insulin and muscle protein anabolism in the bovine. There is limited literature on the effects of feeding fat sources rich in omega-3 polyunsaturated fatty acids, such as fish oil and linseed oil, on metabolism of periparturient dairy cows. Available research has yielded conflicting results which need further clarification. On the other hand, specific isomers of conjugated linoleic acid consistently induce milk fat depression and are able to decrease energy export in milk by periparturient dairy cows. Nonetheless, research is still needed to assess whether these effects will ultimately benefit productivity and health status of periparturient dairy cows. Limitations of available methods to protect fatty acids from ruminal biohydrogenation are also addressed.

  4. Metabolic Response of Pakchoi Leaves to Amino Acid Nitrogen

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-li; YU Wen-juan; ZHOU Qian; HAN Rui-feng; HUANG Dan-feng

    2014-01-01

    Different nitrogen (N) forms may cause changes in the metabolic profiles of plants. However, few studies have been conducted on the effects of amino acid-N on plant metabolic proifles. The main objective of this study was to identify primary metabolites associated with amino acid-N (Gly, Gln and Ala) through metabolic proifle analysis using gas chromatography-mass spectrometry (GC-MS). Plants of pakchoi (Brassica campestris L. ssp. chinensis L.), Huawang and Wuyueman cultivars, were grown with different nitrogen forms (i.e., Gly, Gln, Ala, NO3--N, and N starvation) applied under sterile hydroponic conditions. The fresh weight and plant N accumulation of Huawang were greater than those of Wuyueman, which indicates that the former exhibited better N-use efficiency than the latter. The physiological performances of the applied N forms were generally in the order of NO3--N>Gln>Gly>Ala. The metabolic analysis of leaf polar extracts revealed 30 amino acid N-responsive metabolites in the two pakchoi cultivars, mainly consisting of sugars, amino acids, and organic acids. Changes in the carbon metabolism of pakchoi leaves under amino acid treatments occurred via the accumulation of fructose, glucose, xylose, and arabinose. Disruption of amino acid metabolism resulted in accumulation of endogenous Gly in Gly treatment, Pro in Ala treatment, and Asn in three amino acid (Gly, Gln and Ala) treatments. By contrast, the levels of endogenous Gln and Leu decreased. However, this reduction varied among cultivars and amino acid types. Amino acid-N supply also affected the citric acid cycle, namely, the second stage of respiration, where leaves in Gly, Gln and Ala treatments contained low levels of malic, citric and succinic acids compared with leaves in NO3--N treatments. No signiifcant difference in the metabolic responses was observed between the two cultivars which differed in their capability to use N. The response of primary metabolites in pakchoi leaves to amino acid-N supply

  5. Phytanic acid metabolism in health and disease.

    Science.gov (United States)

    Wanders, Ronald J A; Komen, Jasper; Ferdinandusse, Sacha

    2011-09-01

    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which cannot be beta-oxidized due to the presence of the first methyl group at the 3-position. Instead, phytanic acid undergoes alpha-oxidation to produce pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) plus CO(2). Pristanic acid is a 2-methyl branched-chain fatty acid which can undergo beta-oxidation via sequential cycles of beta-oxidation in peroxisomes and mitochondria. The mechanism of alpha-oxidation has been resolved in recent years as reviewed in this paper, although some of the individual enzymatic steps remain to be identified. Furthermore, much has been learned in recent years about the permeability properties of the peroxisomal membrane with important consequences for the alpha-oxidation process. Finally, we present new data on the omega-oxidation of phytanic acid making use of a recently generated mouse model for Refsum disease in which the gene encoding phytanoyl-CoA 2-hydroxylase has been disrupted.

  6. The relationship between turgor pressure and titratable acidity in mesophyll cells of intact leaves of a Crassulacean-acid-metabolism plant, Kalanchoe daigremontiana Hamet et Perr.

    Science.gov (United States)

    Rygol, J; Winter, K; Zimmermann, U

    1987-12-01

    Day/night changes in turgor pressure (P) and titratable acidity content were investigated in the (Crassulacean-acid-metabolism (CAM) plant Kalanchoe daigremontiana. Measurements of P were made on individual mesophyll cells of intact attached leaves using the pressure-probe technique. Under conditions of high relative humidity, when transpiration rates were minimal, changes in P correlated well with changes in the level of titratable acidity. During the standard 12 h light/12 h dark cycle, maximum turgor pressure (0.15 MPa) occurred at the end of the dark period when the level of titratable acidity was highest (about 300 μeq H(+)·g(-1) fresh weight). A close relationship between P and titratable acidity was also seen in leaves exposed to perturbations of the standard light/dark cycle. (The dark period was either prolonged, or else only CO2-free air was supplied in this period). In plants deprived of irrigation for five weeks, diurnal changes in titratable acidity of the leaves were reduced (ΔH=160 μeq H(+)·g(-1) fresh weight) and P increased from essentially zero at the end of the light period to 0.02 MPa at the end of the dark period. Following more severe water stress (experiments were made on leaves which had been detached for five weeks), P was zero throughout day and night, yet small diurnal changes in titratable acidity were still measured. These findings are discussed in relation to a hypothesis by Lüttge et al. 1975 (Plant Physiol. 56,613-616) for the role of P in the regulation of acidification/de-acidification cycles of plants exhibiting CAM. PMID:24226067

  7. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    Science.gov (United States)

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.

  8. Biobased organic acids production by metabolically engineered microorganisms

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2016-01-01

    expanded as organic acids constitute a key group among top building block chemicals that can be produced from renewable resources. Here we review the current status for production of citric acid and lactic acid, and we highlight the use of modern metabolic engineering technologies to develop high......Bio-based production of organic acids via microbial fermentation has been traditionally used in food industry. With the recent desire to develop more sustainable bioprocesses for production of fuels, chemicals and materials, the market for microbial production of organic acids has been further...... performance microbes for production of succinic acid and 3-hydroxypropionic acid. Also, the key limitations and challenges in microbial organic acids production are discussed...

  9. Fatty acids from diet and microbiota regulate energy metabolism

    OpenAIRE

    Joe Alcock; Lin, Henry C.

    2015-01-01

    A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly ...

  10. Role of brain glutamic acid metabolism changes in neurodegenerative pathologies

    OpenAIRE

    Nina Pavlovna Kanunnikova

    2012-01-01

    Glutamic acid is an essential participant of brain metabolism. It is known that the glutamate is a neurotransmitter in a numerous part of the brain synapses and acts through various ionotropic or metabotropic receptors. Multiple alterations of the brain glutamate system are observed in both acute and chronic brain injures. Glutamate metabolism changes take place in many neurodegenerative pathologies, such as brain ischemia, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyot...

  11. An isozyme of the NADP-malic enzyme of a CAM plant, Aloe arborescens, with variation on conservative amino acid residues.

    Science.gov (United States)

    Honda, H; Akagi, H; Shimada, H

    2000-02-01

    In Aloe arborescens, an obligate CAM plant, Western analysis detected three major isoforms of NADP-malic enzyme (NADP-ME), 72kDa with a pI of 6.0, 65kDa with a pI of 5.6 and 65kDa with a pI of 5.5. Among them, the 65kDa protein with a pI of 5.5 was leaf-specific, and the 65kDa protein with a pI of 5.6 was found only in roots, whereas the 72kDa protein was uniformly detected in both organs. Activity staining indicated enzyme activity of both 65kDa NADP-MEs but little activity of the 72kDa protein. A cDNA clone encoding a leaf-abundant NADP-ME, AME1, was isolated. Deduced amino acid sequence of AME1 showed a high degree of homology to known NADP-MEs, but it was also found that AME1 contained substitutions on five conservative amino acid residues, some of which have been predicted to be important for their enzyme activity. Transgenic rice carrying the aloe AME1 gene efficiently produced an additional 65kDa protein with a pI of 5.5 as an active NADP-ME. These results indicate that AME1 corresponds to the leaf-specific 65kDa NADP-ME, which may be involved in CAM photosynthesis. It was also shown that substitutions of these conservative amino acid residues identified in AME1 still allowed it to give enzyme activity. PMID:10675616

  12. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal;

    2005-01-01

    the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria.......Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...

  13. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  14. Metabolism of hydroxycinnamic acids and their tartaric acid esters by Brettanomyces and Pediococcus in red wines.

    Science.gov (United States)

    Caffeic, p-coumaric, and ferulic acids and their corresponding tartaric acid esters (caftaric, coutaric, and fertaric, respectively) are found in wines in varying concentrations. While Brettanomyces and Pediococcus can utilize the free acids, it is not known whether they can metabolize the correspon...

  15. N-13 labeled amino acids: biodistribution, metabolism and dosimetric considerations

    International Nuclear Information System (INIS)

    With the growing interest in metabolic imaging and with the increasing number of cyclotron/PET facilities, more studies are being performed in animal and humans using short-lived positron-emitting radionuclides. Amino acids labeled either with N-13 or C-11 are one group of compounds being used to study in vivo regional organ (i.e., brain and heart) or tumor metabolism. Of the studies previously reported using C-11 or N-13 labeled amino acids (methionine, alanine, valine, glutamate, glutamine and tryptophan), imaging was restricted mainly to the organ or tissue of interest with little information obtained about the whole-bode distribution of the label. Such data are important for studying interorgan transport of amino acids and for determining accurate dosimetric measurements after intravenous injection of labeled amino acids. The goals of the authors study were to compare the distribution of several N-13 L-amino acids and N-13 ammonia in tumor-bearing mice and to determine the metabolic fate of the label in vivo. The following amino acids were enzymatically labeled using N-13 ammonia: glutamine, glutamate, methionine, α-aminobutyric acid, valine and leucine. 30 references, 2 figures, 14 tables

  16. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S;

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pat......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.......Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy...

  17. The Role of Diet1 in Bile Acid Metabolism

    OpenAIRE

    Lee, Jessica Mei-Ping

    2013-01-01

    Elevated cholesterol levels are associated with increased risk for atherosclerosis, heart disease and stroke. Variations in plasma cholesterol levels among individuals are determined by the interaction of environmental and genetic factors, many of which remain to be identified. This dissertation presents the initial characterization of a novel gene Diet1, the product of which influences plasma cholesterol levels through its effects on bile acid metabolism. Bile acids are synthesized from c...

  18. A Review of the Metabolic Origins of Milk Fatty Acids

    Directory of Open Access Journals (Sweden)

    Anamaria COZMA

    2013-08-01

    Full Text Available Milk fat and its fatty acid profile are important determinants of the technological, sensorial, and nutritional properties of milk and dairy products. The two major processes contributing to the presence of fatty acids in ruminant milk are the mammary lipogenesis and the lipid metabolism in the rumen. Among fatty acids, 4:0 to 12:0, almost all 14:0 and about a half of 16:0 in milk fat derive from de novo synthesis within the mammary gland. De novo synthesis utilizes as precursors acetate and butyrate produced through carbohydrates ruminal fermentation and involves acetyl-CoA carboxylase and fatty acid synthetase as key enzymes. The rest of 16:0 and all of the long-chain fatty acids derive from mammary uptake of circulating lipoproteins and nonesterified fatty acids that originate from digestive absorption of lipids and body fat mobilization. Further, long-chain fatty acids as well as medium-chain fatty acids entering the mammary gland can be desaturated via Δ-9 desaturase, an enzyme that acts by adding a cis-9-double bond on the fatty acid chain. Moreover, ruminal biohydrogenation of dietary unsaturated fatty acids results in the formation of numerous fatty acids available for incorporation into milk fat. Ruminal biohydrogenation is performed by rumen microbial population as a means of protection against the toxic effects of polyunsaturated fatty acids. Within the rumen microorganisms, bacteria are principally responsible for ruminal biohydrogenation when compared to protozoa and anaerobic fungi.

  19. Transcriptional regulation of central amino acid metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Larsen, Rasmus

    2005-01-01

    This thesis describes the functional characterisation of the transcriptional regulators GlnR, ArgR and AhrC of Lactococcus lactis, which are responsible for the control of genes involved in the metabolism of the amino acids glutamine, glutamate and arginine. A chromosomal glnR deletion mutant was ma

  20. Oxygen-18 incorporation into malic acid during nocturnal carbon dioxide fixation in crassulacean acid metabolism plants: a new approach to estimating in vivo carbonic anhydrase activity

    Energy Technology Data Exchange (ETDEWEB)

    Holtum, J.A.M.; Summons, R.; Roeske, C.A.; Comins, H.N.; O' Leary, M.H.

    1984-01-01

    Crassulacean acid metabolism (CAM) plants fix carbon dioxide at night by the carboxylation of phosphoenolpyruvate. If CO2 fixation is conducted with TC YO2, then in the absence of carbonic anhydrase, the malate formed by dark CO2 fixation should also contain high levels of carbon-13 and oxygen-18. Conversely, if carbonic anhydrase is present and highly active, oxygen exchange between CO2 and cellular H2O will occur more rapidly than carboxylation, and the ( TC) malate formed will contain little or no oxygen-18 above the natural abundance level. The presence of oxygen-18 in these molecules can be detected either by nuclear magnetic resonance or by mass spectrometry. Studies of phosphoenolpyruvate carboxylase in the presence and absence of carbonic anhydrase in vitro confirm the validity of the method. When CAM plants are studied by this method, we find that most species show incorporation of a significant amount of oxygen-18. Comparison of these results with results of isotope fractionation and gas exchange studies permits calculation of the in vivo activity of carbonic anhydrase toward HCO3 compared with that of phosphoenolpyruvate carboxylase. The ratio (carbonic anhydrase activity/phosphoenolpyruvate carboxylase activity) is species dependent and varies from a low of about 7 for Ananas comosus to values near 20 for Hoya carnosa and Bryophyllum pinnatum, 40 for Kalanchoee daigremontiana, and 100 or greater for Bryophyllum tubiflorum, Kalanchoee serrata, and Kalanchoae tomentosa. Carbonic anhydrase activity increases relative to phosphoenolpyruvate carboxylase activity at higher temperature. 37 references, 2 figures, 8 tables.

  1. Role of mitochondrial transamination in branched chain amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hutson, S.M.; Fenstermacher, D.; Mahar, C.

    1988-03-15

    Oxidative decarboxylation and transamination of 1-/sup 14/C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso(1-/sup 14/C)valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and (1-/sup 14/C)KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha-keto acids was examined using 20 microM (1-/sup 14/C)KIV and alpha-ketoiso(1-/sup 14/C)caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto-glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using (1-/sup 14/C)leucine and (1-/sup 14/C)valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of (1-/sup 14/C)leucine or (1-/sup 14/C)valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized.

  2. Metabolic evolution of Escherichia coli strains that produce organic acids

    Science.gov (United States)

    Grabar, Tammy; Gong, Wei; Yocum, R Rogers

    2014-10-28

    This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.

  3. Contribution of carbon fixed by Rubisco and PEPC to phloem export in the Crassulacean acid metabolism plant Kalanchoe daigremontiana.

    Science.gov (United States)

    Wild, Birgit; Wanek, Wolfgang; Postl, Wolfgang; Richter, Andreas

    2010-03-01

    Crassulacean acid metabolism (CAM) plants exhibit a complex interplay between CO(2) fixation by phosphoenolpyruvate carboxylase (PEPC) and ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco), and carbon demand for CAM maintenance and growth. This study investigated the flux of carbon from PEPC and direct Rubisco fixation to different leaf carbon pools and to phloem sap over the diurnal cycle. Concentrations and carbon isotope compositions of starch, soluble sugars, and organic acids were determined in leaves and phloem exudates of Kalanchoë daigremontiana Hamet et Perr., and related to CO(2) fixation by PEPC and Rubisco. Three types of leaf carbon pools could be distinguished. (i) Starch and malate pools were dominant and showed a pattern of reciprocal mobilization and accumulation (85/54 and 13/48 mg C g(-1) DW, respective, at the beginning/end of phase I). The carbon isotope composition of these pools was compatible with predominant PEPC fixation (delta(13)C values of -13 and -11 per thousand for starch and malate compared to -11 per thousand of PEPC fixed carbon). (ii) Isotopic composition (-17 per thousand and -14 per thousand) and concentration of glucose and fructose (2 and 3 mg C g(-1) DW, respectively) were not affected by diurnal metabolism, suggesting a low turnover. (iii) Sucrose (1-3 mg C g(-1) DW), in contrast, exhibited large diurnal changes in delta(13)C values (from -17 per thousand in the evening to -12 per thousand in the morning), which were not matched by net changes in sucrose concentration. This suggests a high sucrose turnover, fed by nocturnal starch degradation and direct Rubisco fixation during the day. A detailed dissection of the carbon fixation and mobilization pattern in K. daigremontiana revealed that direct fixation of Rubisco during the light accounted for 30% of phloem sucrose, but only 15% of fixed carbon, indicating that carbon from direct Rubisco fixation was preferentially used for leaf export. PMID:20159885

  4. Reliable Metabolic Flux Estimation in Escherichia coli Central Carbon Metabolism Using Intracellular Free Amino Acids

    Directory of Open Access Journals (Sweden)

    Nobuyuki Okahashi

    2014-05-01

    Full Text Available 13C metabolic flux analysis (MFA is a tool of metabolic engineering for investigation of in vivo flux distribution. A direct 13C enrichment analysis of intracellular free amino acids (FAAs is expected to reduce time for labeling experiments of the MFA. Measurable FAAs should, however, vary among the MFA experiments since the pool sizes of intracellular free metabolites depend on cellular metabolic conditions. In this study, minimal 13C enrichment data of FAAs was investigated to perform the FAAs-based MFA. An examination of a continuous culture of Escherichia coli using 13C-labeled glucose showed that the time required to reach an isotopically steady state for FAAs is rather faster than that for conventional method using proteinogenic amino acids (PAAs. Considering 95% confidence intervals, it was found that the metabolic flux distribution estimated using FAAs has a similar reliability to that of the PAAs-based method. The comparative analysis identified glutamate, aspartate, alanine and phenylalanine as the common amino acids observed in E. coli under different culture conditions. The results of MFA also demonstrated that the 13C enrichment data of the four amino acids is required for a reliable analysis of the flux distribution.

  5. Metabolic engineering of Yarrowia lipolytica for itaconic acid production.

    Science.gov (United States)

    Blazeck, John; Hill, Andrew; Jamoussi, Mariam; Pan, Anny; Miller, Jarrett; Alper, Hal S

    2015-11-01

    Itaconic acid is a naturally produced organic acid with diverse applications as a replacement for petroleum derived products. However, its industrial viability as a bio-replacement has been restricted due to limitations with native producers. In this light, Yarrowia lipolytica is an excellent potential candidate for itaconic acid production due to its innate capacity to accumulate citric acid cycle intermediates and tolerance to lower pH. Here, we demonstrate the capacity to produce itaconic acid in Y. lipolytica through heterologous expression of the itaconic acid synthesis enzyme, resulting in an initial titer of 33 mg/L. Further optimizations of this strain via metabolic pathway engineering, enzyme localization, and media optimization strategies enabled 4.6g/L of itaconic acid to be produced in bioreactors, representing a 140-fold improvement over initial titer. Moreover, these fermentation conditions did not require additional nutrient supplementation and utilized a low pH condition that enabled the acid form of itaconic acid to be produced. Overall yields (0.058 g/g yield from glucose) and maximum productivity of 0.045 g/L/h still provide areas for future strain improvement. Nevertheless, this work demonstrates that Y. lipolytica has the potential to serve as an industrially relevant platform for itaconic acid production.

  6. Taurocholic acid metabolism by gut microbes and colon cancer.

    Science.gov (United States)

    Ridlon, Jason M; Wolf, Patricia G; Gaskins, H Rex

    2016-05-01

    Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID:27003186

  7. Regulation of intestinal protein metabolism by amino acids.

    Science.gov (United States)

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  8. Transcriptome Analysis of Drought-Tolerant CAM plants Agave deserti and Agave tequilana

    OpenAIRE

    Gross, Stephen M.

    2013-01-01

    Agaves are succulent monocotyledonous plants native to hot and arid environments of North America. Because of their adaptations to their environment, including crassulacean acid metabolism (CAM, a water-efficient form of photosynthesis) and existing technologies for ethanol production, agaves have gained attention both as potential lignocellulosic bioenergy feedstocks and models for exploring plant responses to abiotic stress. However, the lack of comprehensive Agave sequence datasets limits ...

  9. De novo transcriptome assembly of drought tolerant CAM plants, Agave deserti and Agave tequilana

    OpenAIRE

    Gross, Stephen M.; Martin, Jeffrey A.; Simpson, June; Abraham-Juarez, María Jazmín; Wang, Zhong; Visel, Axel

    2013-01-01

    Background Agaves are succulent monocotyledonous plants native to xeric environments of North America. Because of their adaptations to their environment, including crassulacean acid metabolism (CAM, a water-efficient form of photosynthesis), and existing technologies for ethanol production, agaves have gained attention both as potential lignocellulosic bioenergy feedstocks and models for exploring plant responses to abiotic stress. However, the lack of comprehensive Agave sequence datasets li...

  10. Metabolism and metabolic inhibition of gamboglc acid in rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    Yi-tong LIU; Kun HAO; Xiao-quan LIU; Guang-Ji WANG

    2006-01-01

    Aim: To study the metabolism of gambogic acid (GA) and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of GA in rat liver microsomes in vitro. Methods: Rat liver micrp,so,rn,e$ were used to perform metabolism studies. Various selective CYP450 inhibitors were used to investigate their effects on the metabolism of GA and the principal CYP450 isoform involved in the formation of major metabolite M1 in rat liver microsomes. Types of inhibition in an enzyme kinetics model were used to model the interaction. Results: GA was rapidly metabolized to two phase Ⅰ metabolites,, M1 and M2, in rat liver microsomes. M1 and M2 were tentatively presumed to be the hydration metabolite and epoxide metabolite of GA, respectively. α-Naphthoflavone uncompetitively inhibited the formation of M1 while ketoconazole, sulfophenazole, diethyl dithiocarbamate and quinidine had little or no inhibitory effects on the formation of M1. Conclusion: GA is rapidly metabolized in rat liver microsomes and M1 is crucial for the elimination of GA. Cytochrome P-450 1A2 is the major rat CYP involved in the metabolism of GA.

  11. Comparative functional genomics of amino acid metabolism of lactic acid bacteria

    NARCIS (Netherlands)

    Pastink, M.I.

    2009-01-01

    The amino acid metabolism of lactic acid bacteria used as starters in industrial fermentations has profound effects on the quality of the fermented foods. The work described in this PhD thesis was initiated to use genomics technologies and a comparative approach to link the gene content of some well

  12. Effect of acute acid loading on acid-base and calcium metabolism

    DEFF Research Database (Denmark)

    Osther, Palle J

    2006-01-01

    OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute non-carbonic acid loading in idiopathic calcium stone-formers and healthy males using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h ammonium chloride loading studies were performed in 12 m...

  13. Structurally modified fatty acids - clinical potential as tracers of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Dudczak, R.; Schmoliner, R.; Angelberger, P.; Knapp, F.F.; Goodman, M.M.

    1985-01-01

    Recently 15-p-iodophenyl-betamethyl-pentadecanoic acid (BMPPA) was proposed for myocardial scintigraphy, as possible probe of metabolic processes other than ..beta..-oxidation. In 19 patients myocardial scintigraphy was done after i.v. BMPPA (2 to 4 mCi). Data were collected (LAO 45/sup 0//14; anterior/5) for 100 minutes in the fasted patients. From heart (H) and liver (L) organ to background (BG) ratios were calculated, and the elimination (E) behavior was analyzed from BG (V. cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl/sub 3//MeOH extraction of plasma samples (90 min. pi) both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with benzoic acid, BMPPA and triglycerides. In urine (0 to 2h pi: 4.1% dose) hippuric acid was found. It is concluded that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. Rate of elimination and plasma analysis indicate the metabolic breakdown of BMPPA. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways. 19 refs., 5 tabs.

  14. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    Science.gov (United States)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  15. Arachidonic Acid-metabolizing Cytochrome P450 Enzymes Are Targets of ω-3 Fatty Acids*

    OpenAIRE

    Arnold, Cosima; Markovic, Marija; Blossey, Katrin; Wallukat, Gerd; Fischer, Robert; Dechend, Ralf; Konkel, Anne; von Schacky, Clemens; Luft, Friedrich C.; Muller, Dominik N.; Rothe, Michael; Schunck, Wolf-Hagen

    2010-01-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against cardiovascular disease by largely unknown mechanisms. We tested the hypothesis that EPA and DHA may compete with arachidonic acid (AA) for the conversion by cytochrome P450 (CYP) enzymes, resulting in the formation of alternative, physiologically active, metabolites. Renal and hepatic microsomes, as well as various CYP isoforms, displayed equal or elevated activities when metabolizing EPA or DHA instead of AA. CYP2C/2J...

  16. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel

    2016-01-01

    Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

  17. Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance.

    Science.gov (United States)

    Meesapyodsuk, Dauenpen; Chen, Yan; Ng, Siew Hon; Chen, Jianan; Qiu, Xiao

    2015-11-01

    Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a "push" (synthesis) and "pull" (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fatty acid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses.

  18. Fatty Acids in Energy Metabolism of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Alexander Panov

    2014-01-01

    Full Text Available In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain’s energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

  19. VARIABLE-THROW CAM

    Science.gov (United States)

    Godsil, E.C.; Robinson, E.Y.

    1963-07-16

    A variable-throw cam comprising inner and outer eccentric sleeves which are adjustably locked together is described. The cam throw is varied by unlocking the inner and outer sleeves, rotating the outer sleeve relative to the inner one until the desired throw is obtained, and locking the sleeves together again. The cam is useful in applications wherein a continuously-variable throw is required, e.g., ram-and-die pressing operations, cyclic fatigue testing of materials, etc. (AEC)

  20. Orchestration of carbohydrate processing for crassulacean acid metabolism.

    Science.gov (United States)

    Borland, Anne M; Guo, Hao-Bo; Yang, Xiaohan; Cushman, John C

    2016-06-01

    The production of phosphoenolpyruvate as a substrate for nocturnal CO2 uptake represents a significant sink for carbohydrate in CAM plants which has to be balanced with the provisioning of carbohydrate for growth and maintenance. In starch-storing CAM species, diversification in chloroplast metabolite transporters, and the deployment of both phosphorolytic and hydrolytic routes of starch degradation accommodate a division of labour in directing C-skeletons towards nocturnal carboxylation or production of sucrose for growth. In soluble-sugar storing CAM plants, the vacuole plays a central role in managing carbon homeostasis. The molecular identities of various types of vacuolar sugar transporters have only been identified for C3 species within the last 10 years. The recent availability of CAM genomes enables the identification of putative orthologues of vacuolar sugar transporters which represent strategic targets for orchestrating the diel provisioning of substrate for nocturnal carboxylation and growth. PMID:27101569

  1. Metabolism of Cholesterol and Bile Acids by the Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Philippe Gérard

    2013-12-01

    Full Text Available The human gastro-intestinal tract hosts a complex and diverse microbial community, whose collective genetic coding capacity vastly exceeds that of the human genome. As a consequence, the gut microbiota produces metabolites from a large range of molecules that host’s enzymes are not able to convert. Among these molecules, two main classes of steroids, cholesterol and bile acids, denote two different examples of bacterial metabolism in the gut. Therefore, cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Moreover, this conversion occurs in a part of the human population only. Conversely, the primary bile acids (cholic and chenodeoxycholic acids are converted to over twenty different secondary bile acid metabolites by the gut microbiota. The main bile salt conversions, which appear in the gut of the whole human population, include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation. If the metabolisms of cholesterol and bile acids by the gut microbiota are known for decades, their consequences on human health and disease are poorly understood and only start to be considered.

  2. Transport and metabolism of glycolic acid by Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    In order to understand the excretion of glycolate from Chlamydomonas reinhardtii, the conditions affecting glycolate synthesis and metabolism were investigated. Although glycolate is synthesized only in the light, the metabolism occurs in the light and dark with greater metabolism in the light due to refixation of photorespiratory CO2. The amount of internal glycolate will affect the metabolism of externally added glycolate. When glycolate synthesis exceeds the metabolic capacity, glycolate is excreted from the cell. The transport of glycolate into the cells occurs very rapidly. Equilibrium is achieved at 40C within the time cells are pelleted by the silicone oil centrifugation technique through a layer of [14C] glycolate. Glycolate uptake does not show the same time, temperature and pH dependencies as diffusion of benzoate. Uptake can be inhibited by treatment of cells with N-ethylmaleimide and stimulated in the presence of valino-mycin/KCl. Acetate and lactate are taken up as quickly as glycolate. The hypothesis was made that glycolate is transported by a protein carrier that transports monocarboxylic acids. The equilibrium concentration of glycolate is dependent on the cell density, implying that there may be a large number of transporter sites and that uptake is limited by substrate availability

  3. Spatial patterns of photosynthesis in thin- and thick-leaved epiphytic orchids: unravelling C3–CAM plasticity in an organ-compartmented way

    Science.gov (United States)

    Rodrigues, Maria Aurineide; Matiz, Alejandra; Cruz, Aline Bertinatto; Matsumura, Aline Tiemi; Takahashi, Cassia Ayumi; Hamachi, Leonardo; Félix, Lucas Macedo; Pereira, Paula Natália; Latansio-Aidar, Sabrina Ribeiro; Aidar, Marcos Pereira Marinho; Demarco, Diego; Freschi, Luciano; Mercier, Helenice; Kerbauy, Gilberto Barbante

    2013-01-01

    Background and Aims A positive correlation between tissue thickness and crassulacean acid metabolism (CAM) expression has been frequently suggested. Therefore, this study addressed the question of whether water availability modulates photosynthetic plasticity in different organs of two epiphytic orchids with distinct leaf thickness. Methods Tissue morphology and photosynthetic mode (C3 and/or CAM) were examined in leaves, pseudobulbs and roots of a thick-leaved (Cattleya walkeriana) and a thin-leaved (Oncidium ‘Aloha’) epiphytic orchid. Morphological features were studied comparing the drought-induced physiological responses observed in each organ after 30 d of either drought or well-watered treatments. Key Results Cattleya walkeriana, which is considered a constitutive CAM orchid, displayed a clear drought-induced up-regulation of CAM in its thick leaves but not in its non-leaf organs (pseudobulbs and roots). The set of morphological traits of Cattleya leaves suggested the drought-inducible CAM up-regulation as a possible mechanism of increasing water-use efficiency and carbon economy. Conversely, although belonging to an orchid genus classically considered as performing C3 photosynthesis, Oncidium ‘Aloha’ under drought seemed to express facultative CAM in its roots and pseudobulbs but not in its leaves, indicating that such photosynthetic responses might compensate for the lack of capacity to perform CAM in its thin leaves. Morphological features of Oncidium leaves also indicated lower efficiency in preventing water and CO2 losses, while aerenchyma ducts connecting pseudobulbs and leaves suggested a compartmentalized mechanism of nighttime carboxylation via phosphoenolpyruvate carboxylase (PEPC) (pseudobulbs) and daytime carboxylation via Rubisco (leaves) in drought-exposed Oncidium plants. Conclusions Water availability modulated CAM expression in an organ-compartmented manner in both orchids studied. As distinct regions of the same orchid could perform

  4. How closely do the delta(13)C values of Crassulacean Acid metabolism plants reflect the proportion of CO(2) fixed during day and night?

    Science.gov (United States)

    Winter, Klaus; Holtum, Joseph A M

    2002-08-01

    The extent to which Crassulacean acid metabolism (CAM) plant delta(13)C values provide an index of the proportions of CO(2) fixed during daytime and nighttime was assessed. Shoots of seven CAM species (Aloe vera, Hylocereus monocanthus, Kalanchoe beharensis, Kalanchoe daigremontiana, Kalanchoe pinnata, Vanilla pauciflora, and Xerosicyos danguyi) and two C(3) species (teak [Tectona grandis] and Clusia sp.) were grown in a cuvette, and net CO(2) exchange was monitored for up to 51 d. In species exhibiting net dark CO(2) fixation, between 14% and 73.3% of the carbon gain occurred in the dark. delta(13)C values of tissues formed inside the cuvette ranged between -28.7 per thousand and -11.6 per thousand, and correlated linearly with the percentages of carbon gained in the light and in the dark. The delta(13)C values for new biomass obtained solely during the dark and light were estimated as -8.7 per thousand and -26.9 per thousand, respectively. For each 10% contribution of dark CO(2) fixation integrated over the entire experiment, the delta(13)C content of the tissue was, thus, approximately 1.8 per thousand less negative. Extrapolation of the observations to plants previously surveyed under natural conditions suggests that the most commonly expressed version of CAM in the field, "the typical CAM plant," involves plants that gain about 71% to 77% of their carbon by dark fixation, and that the isotopic signals of plants that obtain one-third or less of their carbon in the dark may be confused with C(3) plants when identified on the basis of carbon isotope content alone. PMID:12177497

  5. Altered cholesterol and fatty acid metabolism in Huntington disease.

    Science.gov (United States)

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  6. Exploring De Novo metabolic pathways from pyruvate to propionic acid.

    Science.gov (United States)

    Stine, Andrew; Zhang, Miaomin; Ro, Soo; Clendennen, Stephanie; Shelton, Michael C; Tyo, Keith E J; Broadbelt, Linda J

    2016-03-01

    Industrial biotechnology provides an efficient, sustainable solution for chemical production. However, designing biochemical pathways based solely on known reactions does not exploit its full potential. Enzymes are known to accept non-native substrates, which may allow novel, advantageous reactions. We have previously developed a computational program named Biological Network Integrated Computational Explorer (BNICE) to predict promiscuous enzyme activities and design synthetic pathways, using generalized reaction rules curated from biochemical reaction databases. Here, we use BNICE to design pathways synthesizing propionic acid from pyruvate. The currently known natural pathways produce undesirable by-products lactic acid and succinic acid, reducing their economic viability. BNICE predicted seven pathways containing four reaction steps or less, five of which avoid these by-products. Among the 16 biochemical reactions comprising these pathways, 44% were validated by literature references. More than 28% of these known reactions were not in the BNICE training dataset, showing that BNICE was able to predict novel enzyme substrates. Most of the pathways included the intermediate acrylic acid. As acrylic acid bioproduction has been well advanced, we focused on the critical step of reducing acrylic acid to propionic acid. We experimentally validated that Oye2p from Saccharomyces cerevisiae can catalyze this reaction at a slow turnover rate (10(-3) s(-1) ), which was unknown to occur with this enzyme, and is an important finding for further propionic acid metabolic engineering. These results validate BNICE as a pathway-searching tool that can predict previously unknown promiscuous enzyme activities and show that computational methods can elucidate novel biochemical pathways for industrial applications. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:303-311, 2016. PMID:26821575

  7. Fatty-acid metabolism is involved in stress-resistance mechanisms of Caenorhabditis elegans

    OpenAIRE

    Horikawa, Makoto; Sakamoto, Kazuichi

    2009-01-01

    Fatty acids are the major components of the phospholipid bilayer and are involved in several functions of cell membrane. We previously reported that fatty-acid metabolism is involved in the regulation of DAF-2/insulin signal in Caenorhabditis elegans. In this study, we investigate the role of fatty-acid metabolism in stress resistance with respect to daf-16 in nematode. We found that fatty-acid metabolism regulates heat, osmotic, and oxidative-stress resistance in C. elegans. RNA interference...

  8. Metabolic engineering of lactic acid bacteria for the production of nutraceuticals

    NARCIS (Netherlands)

    Hugenholtz, J.; Sybesma, W.; Groot, M.N.; Wisselink, W.; Ladero, V.; Burgess, K.; Sinderen, van D.; Piard, J.C.; Eggink, G.; Smid, E.J.; Savoy, G.; Sesma, F.; Jansen, T.; Hols, P.; Kleerebezem, M.

    2002-01-01

    Lactic acid bacteria display a relatively simple and well-described metabolism where the sugar source is converted mainly to lactic acid. Here we will shortly describe metabolic engineering strategies on the level of sugar metabolism, that lead to either the efficient re-routing of the lactococcal s

  9. Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: Advances and prospects.

    Science.gov (United States)

    Yin, Xian; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian

    2015-11-01

    Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketoglutaric acid, succinic acid, fumaric acid, l-malic acid, and oxaloacetate, which are building-block chemicals with wide applications and huge markets. In this review, we summarize the synthesis pathways of these organic acids and review recent advances in metabolic engineering strategies that enhance organic acid production. We also propose further improvements for the production of organic acids with systems and synthetic biology-guided metabolic engineering strategies.

  10. Amino acid supplementation alters bone metabolism during simulated weightlessness

    Science.gov (United States)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  11. Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

    DEFF Research Database (Denmark)

    Mourtzakis, Marina; Saltin, B.; Graham, T.;

    2006-01-01

    with pyruvate metabolism, and they comprised 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism......During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline...... at 3 h 23 min ± 11 min). Femoral arterial and venous blood, blood flow measurements, and muscle samples were obtained hourly during exercise and recovery (3 h). Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased for the remainder of the exercise bout (P

  12. Metabolism of Flavone-8-acetic Acid in Mice.

    Science.gov (United States)

    Pham, Minh Hien; Auzeil, Nicolas; Regazzetti, Anne; Scherman, Daniel; Seguin, Johanne; Mignet, Nathalie; Dauzonne, Daniel; Chabot, Guy G

    2016-08-01

    Flavone-8-acetic acid (FAA) is a potent antivascular agent in mice but not in humans. Assuming that FAA was bioactivated in mice, we previously demonstrated that 6-OH-FAA was formed from FAA by mouse microsomes but not by human microsomes; its antivascular activity was 2.1- to 15.9-fold stronger than that of FAA, and its antivascular activity was mediated through the Ras homolog gene family (Rho) protein kinase A (RhoA) pathway. The present work aimed to study FAA metabolism in order to verify if 6-OH-FAA is formed in mice. Using synthesized standards and high-performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection and mass spectrometry (MS) analysis, we herein demonstrated, for the first time, that in vitro FAA and its monohydroxylated derivatives could directly undergo phase II metabolism forming glucuronides, and two FAA epoxides were mostly scavenged by NAC and GSH forming corresponding adducts. FAA was metabolized in mice. Several metabolites were formed, in particular 6-OHFAA. The antitumor activity of 6-OH-FAA in vivo is worthy of investigation. PMID:27466491

  13. Oxygen-18 incorporation into malic acid during nocturnal carbon dioxide fixation in crassulacean acid metabolism plants. A new approach to estimating in vivo carbonic anhydrase activity.

    Science.gov (United States)

    Holtum, J A; Summons, R; Roeske, C A; Comins, H N; O'Leary, M H

    1984-06-10

    Crassulacean acid metabolism (CAM) plants fix carbon dioxide at night by the carboxylation of phosphoenolpyruvate. If CO2 fixation is conducted with 13C18O2 , then in the absence of carbonic anhydrase, the malate formed by dark CO2 fixation should also contain high levels of carbon-13 and oxygen-18. Conversely, if carbonic anhydrase is present and highly active, oxygen exchange between CO2 and cellular H2O will occur more rapidly than carboxylation, and the [13C] malate formed will contain little or no oxygen-18 above the natural abundance level. The presence of oxygen-18 in these molecules can be detected either by nuclear magnetic resonance (using the oxygen-18 effect on the carbon-13 chemical shift of the carboxyl carbon) or by mass spectrometry (comparing the ions at three and five units above the molecular weight with that one unit above). Studies of phosphoenolpyruvate carboxylase in the presence and absence of carbonic anhydrase in vitro confirm the validity of the method. When CAM plants are studied by this method, we find that most species show incorporation of a significant amount of oxygen-18. Comparison of these results with results of isotope fractionation and gas exchange studies permits calculation of the in vivo activity of carbonic anhydrase toward HCO-3 compared with that of phosphoenolpyruvate carboxylase. The ratio (carbonic anhydrase activity/phosphoenolpyruvate carboxylase activity) is species dependent and varies from a low of about 7 for Ananas comosus to values near 20 for Hoya carnosa and Bryophyllum pinnatum , 40 for Kalancho ë daigremontiana , and 100 or greater for Bryophyllum tubiflorum , Kalancho ë serrata, and Kalancho ë tomentosa. Carbonic anhydrase activity increases relative to phosphoenolpyruvate carboxylase activity at higher temperature. PMID:6427227

  14. Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

    NARCIS (Netherlands)

    van Straten, Esther M. E.; Bloks, Vincent W.; van Dijk, Theo H.; Baller, Julius F. W.; Huijkman, Nicolette C. A.; Kuipers, Irma; Verkade, Henkjan J.; Plosch, Torsten

    2012-01-01

    Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. Objective: We aim

  15. Metabolically engineered cells for the production of polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    2005-01-01

    The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves improvem......The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves...... improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and/or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other...... enzymes involved in biosynthesis of the precursor for PUFAs, or codon optimization of the heterologous genes, or expression of heterologous enzymes involved in the biosynthesis of the precursor for PUFAs....

  16. Dietary trans-fatty acids and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Zdzisław Kochan

    2010-12-01

    Full Text Available Trans-fatty acids (TFAs, products of partial hydrogenation of vegetable oils, have become more prevalent in our diet since the 1960s, when they replaced animal fats. TFAs also occur naturally in meat and dairy products from ruminants. There is growing evidence that dietary trans-fatty acids may increase the risk of metabolic syndrome. Several studies have demonstrated adverse effects of TFAs on plasma lipids and lipoproteins. In dietary trials, trans-fatty acids have been shown to raise the total cholesterol/HDL cholesterol ratio and Lp(a levels in blood. Moreover, a high intake of TFAs has been associated with an increased risk of coronary heart disease. Prospective cohort studies have shown that dietary trans-fatty acids promote abdominal obesity and weight gain. In addition, it appears that TFA consumption may be associated with the development of insulin resistance and type 2 diabetes. The documented adverse health effects of TFAs emphasise the importance of efforts to reduce the content of partially hydrogenated vegetable oils in foods.

  17. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera, G.A.; Schop, D.; Spitters, T.W.; Dijkhuizen, R.; Bracke, M.; Bruijn, J.D.; Martens, D.E.; Karperien, M.; Boxtel, van A.J.B.; Blitterswijk, van C.A.

    2012-01-01

    The nutritional requirements of stem cells have not been determined; in particular, the amino acid metabolism of stem cells is largely unknown. In this study, we investigated the amino acid metabolism of human mesenchymal stem cells (hMSCs), with focus on two questions: Which amino acids are consume

  18. Defining meal requirements for protein to optimize metabolic roles of amino acids

    Science.gov (United States)

    Dietary protein provides essential amino acids (EAAs) for the synthesis of new proteins plus an array of other metabolic functions; many of these functions are sensitive to postprandial plasma and intracellular amino acid concentrations. Recent research has focused on amino acids as metabolic signal...

  19. CAM and NK Cells

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Takeda

    2004-01-01

    Full Text Available It is believed that tumor development, outgrowth and metastasis are under the surveillance of the immune system. Although both innate and acquired immune systems play roles, innate immunity is the spearhead against tumors. Recent studies have revealed the critical role of natural killer (NK cells in immune surveillance and that NK cell activity is considerably influenced by various agents, such as environmental factors, stress, foods and drugs. Some of these NK cell stimulants have been used in complementary and alternative medicine (CAM since ancient times. Therefore, the value of CAM should be re-evaluated from this point of view. In this review, we overview the intimate correlation between NK cell functions and CAM agents, and discuss possible underlying mechanisms mediating this. In particular, neuro-immune crosstalk and receptors for CAM agents are the most important and interesting candidates for such mechanisms.

  20. Synthetic biology as it relates to CAM photosynthesis: challenges and opportunities.

    Science.gov (United States)

    DePaoli, Henrique C; Borland, Anne M; Tuskan, Gerald A; Cushman, John C; Yang, Xiaohan

    2014-07-01

    To meet future food and energy security needs, which are amplified by increasing population growth and reduced natural resource availability, metabolic engineering efforts have moved from manipulating single genes/proteins to introducing multiple genes and novel pathways to improve photosynthetic efficiency in a more comprehensive manner. Biochemical carbon-concentrating mechanisms such as crassulacean acid metabolism (CAM), which improves photosynthetic, water-use, and possibly nutrient-use efficiency, represent a strategic target for synthetic biology to engineer more productive C3 crops for a warmer and drier world. One key challenge for introducing multigene traits like CAM onto a background of C3 photosynthesis is to gain a better understanding of the dynamic spatial and temporal regulatory events that underpin photosynthetic metabolism. With the aid of systems and computational biology, vast amounts of experimental data encompassing transcriptomics, proteomics, and metabolomics can be related in a network to create dynamic models. Such models can undergo simulations to discover key regulatory elements in metabolism and suggest strategic substitution or augmentation by synthetic components to improve photosynthetic performance and water-use efficiency in C3 crops. Another key challenge in the application of synthetic biology to photosynthesis research is to develop efficient systems for multigene assembly and stacking. Here, we review recent progress in computational modelling as applied to plant photosynthesis, with attention to the requirements for CAM, and recent advances in synthetic biology tool development. Lastly, we discuss possible options for multigene pathway construction in plants with an emphasis on CAM-into-C3 engineering.

  1. Myocardial metabolism of pantothenic acid in chronically diabetic rats.

    Science.gov (United States)

    Beinlich, C J; Naumovitz, R D; Song, W O; Neely, J R

    1990-03-01

    Transport and metabolism of [3H]pantothenic acid ([3H]Pa) was investigated in hearts from control and streptozotocin-induced diabetic rats. In isolated perfused hearts from control animals, the transport of [3H]Pa was linear over 3 h of perfusion when 11 mM glucose was the only exogenous substrate. The in vitro transport of [3H]Pa by hearts from 48-h diabetic rats was reduced by 65% compared to controls and was linear over 2 h of perfusion with no further accumulation of Pa during the third hour. The defect in transport observed in vitro could be corrected by in vivo treatment with 4 U Lente insulin/day for 2 days. In vitro addition of insulin in the presence of 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate had no effect on [3H]Pa transport in hearts from 48-h diabetic rats during 3 h of perfusion. Accumulation of [3H]Pa was not inhibited by inclusion of 0.7 mM amino acids, 1 mM carnitine, 50 microM mersalic acid or 1 mM panthenol, pantoyllactone or pantoyltaurine. Uptake was inhibited by 1 mM nonanoic, octanoic or heptanoic acid, 0.1 mM biotin or 0.25 mM probenecid, suggesting a requirement for the terminal carboxyl group for transport. Transport of pantothenic acid was reduced in hearts from diabetic rats within 24 h of injection of streptozotocin. In vitro accumulation of [3H]Pa decreased to 10% of control 1 week after streptozotocin injection and then remained at 30% of the control value over 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141362

  2. Metabolism of hydroxycinnamic acids and esters by Brettanomyces in different red wines

    Science.gov (United States)

    Depending on the cultivars and other factors, differing concentrations of hydroxycinnamic acids (caffeic, p-coumaric, and ferulic acids) and their corresponding tartaric acid esters (caftaric, coutaric, and fertaric acid, respectively) are found in red wines. Hydroxycinnamic acids are metabolized by...

  3. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    Science.gov (United States)

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  4. Dynamics of human whole body amino acid metabolism

    International Nuclear Information System (INIS)

    The mechanism of regulation of the nitrogen metabolism in humans under various nutritional and physiological states was examined using stable isotopes. In the simultaneous continuous infusion of 1- [13] - leucine and α- [15N]- lysine, their fluxed decreased when individuals received lower protein intake. The rates of oxidation and incorporation into body proteins of leucine changed in parallel with the protein intake. Such effects of diet on whole body leucine kinetics were modified by the energy state and dietary energy level. The nitrogen balance was also improved by an excess level of dietary energy. When the intake of dietary protein was lowered below the maintenance level, the whole body flux and de novo synthesis of glycine were lowered, but alanine synthesis was clearly increased. The intravenous infusion of glucose at 4 mg/kg.min, which causes increase in excess blood sugar and plasma insulin, increased the alanine flux, but had no effect on the glycine flux. The rate of albumin synthesis, determined by giving 15N-glycine orally every 3 hr, decreased with the lowered intake of dietary protein in young men, but not in elderly men. This explains why the serum albumin synthesis increases with the increase in the intake of dietary protein in young men, but not in elderly men. The rate of whole body protein synthesis in young men receiving the L-amino acid diets providing with the required intake of specific amino acid was much lower than that in the men receiving the diets providing with generous intake of specific amino acid. Thus the control mechanism to maintain the homeostasis of body nitrogen and amino acids is related in some unknown way to the nutritional requirement of the hosts. (Kaihara, S.)

  5. Leaf anatomical traits which accommodate the facultative engagement of crassulacean acid metabolism in tropical trees of the genus Clusia.

    Science.gov (United States)

    Barrera Zambrano, V Andrea; Lawson, Tracy; Olmos, Enrique; Fernández-García, Nieves; Borland, Anne M

    2014-07-01

    Succulence and leaf thickness are important anatomical traits in CAM plants, resulting from the presence of large vacuoles to store organic acids accumulated overnight. A higher degree of succulence can result in a reduction in intercellular air space which constrains internal conductance to CO2. Thus, succulence presents a trade-off between the optimal anatomy for CAM and the internal structure ideal for direct C3 photosynthesis. This study examined how plasticity for the reversible engagement of CAM in the genus Clusia could be accommodated by leaf anatomical traits that could facilitate high nocturnal PEPC activity without compromising the direct day-time uptake of CO2 via Rubisco. Nine species of Clusia ranging from constitutive C3 through C3/CAM intermediates to constitutive CAM were compared in terms of leaf gas exchange, succulence, specific leaf area, and a range of leaf anatomical traits (% intercellular air space (IAS), length of mesophyll surface exposed to IAS per unit area, cell size, stomatal density/size). Relative abundances of PEPC and Rubisco proteins in different leaf tissues of a C3 and a CAM-performing species of Clusia were determined using immunogold labelling. The results indicate that the relatively well-aerated spongy mesophyll of Clusia helps to optimize direct C3-mediated CO2 fixation, whilst enlarged palisade cells accommodate the potential for C4 carboxylation and nocturnal storage of organic acids. The findings provide insight on the optimal leaf anatomy that could accommodate the bioengineering of inducible CAM into C3 crops as a means of improving water use efficiency without incurring detrimental consequences for direct C3-mediated photosynthesis.

  6. Metabolism of food phenolic acids by Lactobacillus plantarum CECT 748T

    OpenAIRE

    Rodríguez, Héctor; Landete, José María; Rivas, Blanca de las; Muñoz, Rosario

    2008-01-01

    Phenolic acids account for almost one third of the dietary phenols and are associated with organoleptic, nutritional and antioxidant properties of foods. This study was undertaken to assess the ability of Lactobacillus plantarum CECT 748T to metabolize 19 food phenolic acids. Among the hydroxycinnamic acids studied, only p-coumaric, caffeic, ferulic and m-coumaric acids were metabolized by L. plantarum. Cultures of L. plantarum produced ethyl and vinyl derivatives from p-coumaric and...

  7. PreCam

    Energy Technology Data Exchange (ETDEWEB)

    Allam, Sahar S. [Fermilab; Tucker, Douglas L. [Fermilab

    2015-01-01

    The Dark Energy Survey (DES) will be taking the next step in probing the properties of Dark Energy and in understanding the physics of cosmic acceleration. A step towards the photometric calibration of DES is to have a quick, bright survey in the DES footprint (PreCam), using a pre-production set of the Dark Energy Camera (DECam) CCDs and a set of 100 mm×100 mm DES filters. The objective of the PreCam Survey is to create a network of calibrated DES grizY standard stars that will be used for DES nightly calibrations and to improve the DES global relative calibrations. Here, we describe the first year of PreCam observation, results, and photometric calibrations.

  8. Effects of Butter and Phytanic acid intake on metabolic parameters and T-cell polarization

    DEFF Research Database (Denmark)

    Drachmann, Tue

    e.g. fatty acid composition of the diet, are important factors with regard to development of metabolic syndrome. There is a controversy between the fact that several studies has shown that intake of saturated fatty acids are strongly correlated to the development of metabolic related diseases......The still growing obesity epidemic is a major risk for our society, as it is associated with the development of the so called metabolic syndrome, which is a clinical diagnosis correlated to development of metabolic disorders. Lack of physical activity, excess energy intake, and nutritional factors...... dairy fat in general and phytanic acid on metabolic parameters, we performed several studies. First, we investigated effects on hepatic lipid metabolism, glucose homeostasis, and circulating metabolic markers, of high fat diets based on butter from high- or low-yield production, a diet based on high...

  9. CAMS achievements in 1995

    Energy Technology Data Exchange (ETDEWEB)

    Berg, Oe.; Fantoni, P.; Iguchi, Y.; Meyer, G.; Soerensen, A.; Dyck, C. van

    1996-01-01

    CAMS (Computerized Accident Management Support) is a system being developed as a joint research activity at the Halden Reactor Project with additional financing from the Swedish Nuclear Inspectorate (SKI) and the Nordic NKS/RAK-2 project. Three types of users are envisaged: the staff in the control room, the staff in the technical support centre and the staff at a national emergency centre. It is still an experimental system. The Swedish Nuclear Inspectorate kindly accepted to test CAMS at a safety exercise on the 4th of May, 1995. CAMS is designed assuming automatic data transfer from the plant. Missing the data link, a simulator running in the next room was updated now and then with data received by phone. As seen from CAMS, it did not matter if the data came from a fake plant or from a real plant, except that the data were delayed. Overall, it seemed that CAMS can be a very important tool for a national authority. A data link from the plant would increase its usefulness. Several comments on design features were collected and will be used to improve the system. The model needs more inputs to control the main parameters, and a larger repertoire of fault conditions should be put into the model. In the second half of 1995 the work on CAMS has concentrated upon designing new modules for signal validation, tracking simulation and state identification. This will provide better capabilities for on-line monitoring and assessment of the plant state. Further, it has been proposed to introduce Probabilistic Safety Assessment (PSA) to assist in risk monitoring. A first prototype has been made on a personal computer showing the main features of such a PSA module. (au).

  10. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    Directory of Open Access Journals (Sweden)

    Seher Balaban

    2015-01-01

    Full Text Available Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

  11. Targeting amino acid metabolism in cancer growth and anti-tumor immune response

    Institute of Scientific and Technical Information of China (English)

    Elitsa; Ananieva

    2015-01-01

    Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.

  12. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  13. Metabolism of nonesterified and esterified hydroxycinnamic acids in red wines by Brettanomyces bruxellensis

    Science.gov (United States)

    While Brettanomyces can metabolize non–esterified hydroxycinnamic acids found in grape musts/wines (caffeic, p–coumaric, and ferulic acids), it was not known whether this yeast could utilize the corresponding tartaric acid esters (caftaric, p–coutaric, and fertaric acids, respectively). Red wines fr...

  14. Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels.

    Science.gov (United States)

    Glawischnig, E; Gierl, A; Tomas, A; Bacher, A; Eisenreich, W

    2001-03-01

    Information on metabolic networks could provide the basis for the design of targets for metabolic engineering. To study metabolic flux in cereals, developing maize (Zea mays) kernels were grown in sterile culture on medium containing [U-(13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and sitosterol were isolated from kernels as well as from the cobs, and their (13)C isotopomer compositions were determined by quantitative nuclear magnetic resonance spectroscopy. The highly specific labeling patterns were used to analyze the metabolic pathways leading to amino acids and the triterpene on a quantitative basis. The data show that serine is generated from phosphoglycerate, as well as from glycine. Lysine is formed entirely via the diaminopimelate pathway and sitosterol is synthesized entirely via the mevalonate route. The labeling data of amino acids and sitosterol were used to reconstruct the labeling patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate, phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed quantitative information about carbon flux in the intermediary metabolism of developing maize kernels. Exogenous acetate served as an efficient precursor of sitosterol, as well as of amino acids of the aspartate and glutamate family; in comparison, metabolites formed in the plastidic compartments showed low acetate incorporation. PMID:11244098

  15. Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes.

    Science.gov (United States)

    Ow, Yin-Yin; Stupans, Ieva

    2003-06-01

    Gallic acid and its structurally related compounds are found widely distributed in fruits and plants. Gallic acid, and its catechin derivatives are also present as one of the main phenolic components of both black and green tea. Esters of gallic acid have a diverse range of industrial uses, as antioxidants in food, in cosmetics and in the pharmaceutical industry. In addition, gallic acid is employed as a source material for inks, paints and colour developers. Studies utilising these compounds have found them to possess many potential therapeutic properties including anti-cancer and antimicrobial properties. In this review, studies of the effects of gallic acid, its esters, and gallic acid catechin derivatives on Phase I and Phase II enzymes are examined. Many published reports of the effects of the in vitro effects of gallic acid and its derivatives on drug metabolising enzymes concern effects directly on substrate (generally drug or mutagen) metabolism or indirectly through observed effects in Ames tests. In the case of the Ames test an antimutagenic effect may be observed through inhibition of CYP activation of indirectly acting mutagens and/or by scavenging of metabolically generated mutagenic electrophiles. There has been considerable interest in the in vivo effects of the gallate esters because of their incorporation into foodstuffs as antioxidants and in the catechin gallates with their potential role as chemoprotective agents. Principally an induction of Phase II enzymes has been observed however more recent studies using HepG2 cells and primary cultures of human hepatocytes provide evidence for the overall complexity of actions of individual components versus complex mixtures, such as those in food. Further systematic studies of mechanisms of induction and inhibition of drug metabolising enzymes by this group of compounds are warranted in the light of their distribution and consequent ingestion, current uses and suggested therapeutic potential. However, it

  16. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism.

    Science.gov (United States)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich; Bäckhed, Fredrik

    2016-07-12

    The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition. PMID:27320064

  17. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants). Final report

    Energy Technology Data Exchange (ETDEWEB)

    Loewus, F.A. [Washington State Univ., Pullman, WA (United States). Inst. of Biological Chemistry; Seib, P.A. [Kansas State Univ., Manhattan, KS (United States). Dept. of Grain Science and Industry

    1991-12-31

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  18. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants)

    Energy Technology Data Exchange (ETDEWEB)

    Loewus, F.A. (Washington State Univ., Pullman, WA (United States). Inst. of Biological Chemistry); Seib, P.A. (Kansas State Univ., Manhattan, KS (United States). Dept. of Grain Science and Industry)

    1991-01-01

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  19. Metabolic carbon fluxes and biosynthesis of polyhydroxyalkanoates in Ralstonia eutropha on short chain fatty acids.

    Science.gov (United States)

    Yu, Jian; Si, Yingtao

    2004-01-01

    Short chain fatty acids such as acetic, propionic, and butyric acids can be synthesized into polyhydroxyalkanoates (PHAs) by Ralstonia eutropha. Metabolic carbon fluxes of the acids in living cells have significant effect on the yield, composition, and thermomechanical properties of PHA bioplastics. Based on the general knowledge of central metabolism pathways and the unusual metabolic pathways in R. eutropha, a metabolic network of 41 bioreactions is constructed to analyze the carbon fluxes on utilization of the short chain fatty acids. In fed-batch cultures with constant feeding of acid media, carbon metabolism and distribution in R. eutropha were measured involving CO2, PHA biopolymers, and residual cell mass. As the cells underwent unsteady state metabolism and PHA biosynthesis under nitrogen-limited conditions, accumulative carbon balance was applied for pseudo-steady-state analysis of the metabolic carbon fluxes. Cofactor NADP/NADPH balanced between PHA synthesis and the C3/C4 pathway provided an independent constraint for solution of the underdetermined metabolic network. A major portion of propionyl-CoA was directed to pyruvate via the 2-methylcitrate cycle and further decarboxylated to acetyl-CoA. Only a small amount of propionate carbon (acetic acid in the medium. Malate is the node of the C3/C4 pathway and TCA cycle and its decarboxylation to dehydrogenation ranges from 0.33 to 1.28 in response to the demands on NADPH and oxaloacetate for short chain fatty acids utilization. PMID:15296425

  20. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available OBJECTIVE: Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. METHODS: The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. RESULTS: The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. CONCLUSION: Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  1. Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus.

    Science.gov (United States)

    Kulkarni, Sameer S; Salehzadeh, Firoozeh; Fritz, Tomas; Zierath, Juleen R; Krook, Anna; Osler, Megan E

    2012-02-01

    The delicate homeostatic balance between glucose and fatty acid metabolism in relation to whole-body energy regulation is influenced by mitochondrial function. We determined expression and regulation of mitochondrial enzymes including pyruvate dehydrogenase kinase (PDK) 4, PDK2, carnitine palmitoyltransferase 1b, and malonyl-coenzyme A decarboxylase in skeletal muscle from people with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM). Vastus lateralis biopsies were obtained from NGT (n = 79) or T2DM (n = 33) men and women matched for age and body mass index. A subset of participants participated in a 4-month lifestyle intervention program consisting of an unsupervised walking exercise. Muscle biopsies were analyzed for expression and DNA methylation status. Primary myotubes were derived from biopsies obtained from NGT individuals for metabolic studies. Cultured skeletal muscle was exposed to agents mimicking exercise activation for messenger RNA (mRNA) expression analysis. The mRNA expression of PDK4, PDK2, and malonyl-coenzyme A decarboxylase was increased in skeletal muscle from T2DM patients. Methylation of the PDK4 promoter was reduced in T2DM and inversely correlated with PDK4 expression. Moreover, PDK4 expression was positively correlated with body mass index, blood glucose, insulin, C peptide, and hemoglobin A(1c). A lifestyle intervention program resulted in increased PDK4 mRNA expression in NGT individuals, but not in those with T2DM. Exposure to caffeine or palmitate increased PDK4 mRNA in a cultured skeletal muscle system. Our findings reveal that skeletal muscle expression of PDK4 and related genes regulating mitochondrial function reflects alterations in substrate utilization and clinical features associated with T2DM. Furthermore, hypomethylation of the PDK4 promoter in T2DM coincided with an impaired response of PDK4 mRNA after exercise. PMID:21816445

  2. Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

    Science.gov (United States)

    Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-07-01

    It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

  3. Eicosapentaenoic acid modulates fatty acid metabolism and inflammation in Psammomys obesus.

    Science.gov (United States)

    Atek-Mebarki, Feriel; Hichami, Aziz; Abdoul-Azize, Souleymane; Bitam, Arezki; Koceïr, Elhadj Ahmed; Khan, Naim Akhtar

    2015-02-01

    The desert gerbil, Psammomys obesus, is a unique polygenic animal model of metabolic syndrome (insulin resistance, obesity and type 2 diabetes), and these pathological conditions resemble to those in human beings. In this study, the animals were fed ad libitum either a natural diet (ND) which contained desertic halophile plants or a standard laboratory diet (STD) or a diet which contained eicosapentaenoic acid (EPA), hence, termed as EPA diet (EPAD). In EPAD, 50% of total lipid content was replaced by EPA oil. By employing real-time PCR, we assessed liver expression of key genes involved in fatty acid metabolism such as PPAR-α, SREBP-1c, LXR-α and CHREBP. We also studied the expression of two inflammatory genes, i.e., TNF-α and IL-1β, in liver and adipose tissue of these animals. The STD, considered to be a high caloric diet for this animal, triggered insulin resistance and high lipid levels, along with high hepatic SREBP-1c, LXR-α and CHREBP mRNA expression. TNF-α and IL-1β mRNA were also high in liver of STD fed animals. Feeding EPAD improved plasma glucose, insulin and triacylglycerol levels along with hepatic lipid composition. These observations suggest that EPA exerts beneficial effects in P. obesus.

  4. L-Lactic acid production from glycerol coupled with acetic acid metabolism by Enterococcus faecalis without carbon loss.

    Science.gov (United States)

    Murakami, Nao; Oba, Mana; Iwamoto, Mariko; Tashiro, Yukihiro; Noguchi, Takuya; Bonkohara, Kaori; Abdel-Rahman, Mohamed Ali; Zendo, Takeshi; Shimoda, Mitsuya; Sakai, Kenji; Sonomoto, Kenji

    2016-01-01

    Glycerol is a by-product in the biodiesel production process and considered as one of the prospective carbon sources for microbial fermentation including lactic acid fermentation, which has received considerable interest due to its potential application. Enterococcus faecalis isolated in our laboratory produced optically pure L-lactic acid from glycerol in the presence of acetic acid. Gas chromatography-mass spectrometry analysis using [1, 2-(13)C2] acetic acid proved that the E. faecalis strain QU 11 was capable of converting acetic acid to ethanol during lactic acid fermentation of glycerol. This indicated that strain QU 11 restored the redox balance by oxidizing excess NADH though acetic acid metabolism, during ethanol production, which resulted in lactic acid production from glycerol. The effects of pH control and substrate concentration on lactic acid fermentation were also investigated. Glycerol and acetic acid concentrations of 30 g/L and 10 g/L, respectively, were expected to be appropriate for lactic acid fermentation of glycerol by strain QU 11 at a pH of 6.5. Furthermore, fed-batch fermentation with 30 g/L glycerol and 10 g/L acetic acid wholly exhibited the best performance including lactic acid production (55.3 g/L), lactic acid yield (0.991 mol-lactic acid/mol-glycerol), total yield [1.08 mol-(lactic acid and ethanol)]/mol-(glycerol and acetic acid)], and total carbon yield [1.06 C-mol-(lactic acid and ethanol)/C-mol-(glycerol and acetic acid)] of lactic acid and ethanol. In summary, the strain QU 11 successfully produced lactic acid from glycerol with acetic acid metabolism, and an efficient fermentation system was established without carbon loss.

  5. Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells.

    Science.gov (United States)

    Masur, F; Benesch, F; Pfannkuche, H; Fuhrmann, H; Gäbel, G

    2016-04-01

    Conjugated linoleic acids (CLA), particularly cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12), are used as feed additives to adapt to constantly increasing demands on the performance of lactating cows. Under these feeding conditions, the rumen wall, and the rumen epithelial cells (REC) in particular, are directly exposed to high amounts of CLA. This study determined the effect of CLA on the fatty acid (FA) metabolism of REC and expression of genes known to be modulated by FA. Cultured REC were incubated with c9t11, t10c12, and the structurally similar FA linoleic acid (LA), oleic acid (OA), and trans-vaccenic acid (TVA) for 48 h at a concentration of 100µM. Cellular FA levels were determined by gas chromatography. Messenger RNA expression levels of stearoyl-CoA desaturase (SCD) and monocarboxylate transporter (MCT) 1 and 4 were quantified by reverse transcription-quantitative PCR. Fatty acid evaluation revealed significant effects of CLA, LA, OA, and TVA on the amount of FA metabolites of β-oxidation and elongation and of metabolites related to desaturation by SCD. The observed changes in FA content point (among others) to the ability of REC to synthesize c9t11 from TVA endogenously. The mRNA expression levels of SCD identified a decrease after CLA, LA, OA, or TVA treatment. In line with the changes in mRNA expression, we found reduced amounts of C16:1n-7 cis-9 and C18:1n-9 cis-9, the main products of SCD. The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) α antagonist suggested that activation of PPARα is involved in the changes of MCT1, MCT4, and SCD mRNA expression induced by c9t11. Participation of PPARγ in the changes of MCT1 and SCD mRNA expression was shown by the application of the respective antagonist. The study demonstrates that exposure to CLA affects both FA metabolism and regulatory pathways within REC. PMID

  6. Fatty acid digestion, synthesis and metabolism in broiler chickens and pigs

    NARCIS (Netherlands)

    Smink, W.

    2012-01-01


    The impact of variation in the composition of dietary fat on digestion, metabolism and synthesis of fatty acids was studied in broiler chickens and in pigs. In young broiler chickens, digestion of unsaturated fatty acids was substantially higher compared with that of saturated fatty acids. Po

  7. Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition.

    Science.gov (United States)

    Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-07-01

    Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle "quality" decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies. PMID:27422520

  8. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Directory of Open Access Journals (Sweden)

    Roze Ludmila V

    2010-08-01

    Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

  9. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Science.gov (United States)

    2010-01-01

    Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary

  10. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin;

    2015-01-01

    (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants. CONCLUSIONS/INTERPRETATION: Type 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate......AIMS/HYPOTHESIS: The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite...... showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH, GATM, NOS1 and GLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation...

  11. Effect of Dietary Fatty Acids on Human Lipoprotein Metabolism: A Comprehensive Update

    Directory of Open Access Journals (Sweden)

    Esther M.M. Ooi

    2015-06-01

    Full Text Available Dyslipidemia is a major risk factor for cardiovascular disease (CVD. Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA consumption diminished hepatic triglyceride-rich lipoprotein (TRL secretion and enhanced TRL to low-density lipoprotein (LDL conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids.

  12. The ins and outs of maternal-fetal fatty acid metabolism.

    Science.gov (United States)

    Bobiński, Rafał; Mikulska, Monika

    2015-01-01

    Fatty acids (FAs) are one the most essential substances in intrauterine human growth. They are involved in a number of energetic and metabolic processes, including the growth of cell membranes, the retina and the nervous system. Fatty acid deficiency and disruptions in the maternal-placental fetal metabolism of FAs lead to malnutrition of the fetus, hypotrophy and preterm birth. What is more, metabolic diseases and cardiovascular conditions may appear later in life. Meeting a fetus' need for FAs is dependent on maternal diet and on the efficiency of the placenta in transporting FAs to fetal circulation. "Essential fatty acids" are among the most important FAs during the intrauterine growth period. These are α-linolenic acid, which is a precursor of the n-3 series, linoleic acid, which is a precursor of the n-6 series and their derivatives, represented by docosahexaenoic acid and arachidonic acid. The latest studies have shown that medium-chain fatty acids also play a significant role in maternal-fetal metabolism. These FAs have significant effect on the transformation of the precursors into DHA, which may contribute to a relatively stable supply of DHA - even in pregnant women whose diet is low in FAs. The review discusses the problem of fatty acid metabolism at the intersection between a pregnant woman and her child with reference to physiological pregnancy, giving birth to a healthy child, intrauterine growth restriction, preterm birth and giving birth to a small for gestational age child. PMID:26345097

  13. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Directory of Open Access Journals (Sweden)

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  14. Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production.

    Directory of Open Access Journals (Sweden)

    Caroline Colijn

    2009-08-01

    Full Text Available Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression, extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB. Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data.

  15. Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

    Science.gov (United States)

    Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

    2016-04-01

    In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short

  16. Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

    OpenAIRE

    Smith, D. M.; Walsh, C E; DeChatelet, L R; Waite, M.

    1983-01-01

    The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A2318...

  17. Visualizing digestive organ morphology and function using differential fatty acid metabolism in live zebrafish

    OpenAIRE

    Carten, Juliana Debrito; Bradford, Mary Katherine; Farber, Steven Arthur

    2011-01-01

    Lipids are essential for cellular function as sources of fuel, critical signaling molecules and membrane components. Deficiencies in lipid processing and transport underlie many metabolic diseases. To better understand metabolic function as it relates to disease etiology, a whole animal approach is advantageous, one in which multiple organs and cell types can be assessed simultaneously in vivo. Towards this end, we have developed an assay to visualize fatty acid (FA) metabolism in larval zebr...

  18. Gut microbiota and nuclear receptors in bile acid and lipid metabolism : bile acids, more than soaps

    NARCIS (Netherlands)

    Out, Carolien

    2014-01-01

    Metabolic syndrome refers to the combination of obesity, hypertension, dyslipidemia and insulin resistance. Metabolic syndrome increases the chance on cardiovascular disease and type 2 diabetes. Strategies to prevent and treat these metabolic derangements are therefore urgently needed. For this purp

  19. BIOCONCENTRATION AND METABOLISM OF ALL-TRANS RETINOIC ACID BY RANA SYLVATICA AND RANA CLAMITANS TADPOLES

    Science.gov (United States)

    Retinoids, which are Vitamin A derivatives, are important signaling molecules that regulate processes critical for development in all vertebrates. The objective of our study was to examine uptake and metabolism of all-trans retinoic acid...

  20. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  1. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites.

    Science.gov (United States)

    Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

    2011-08-23

    Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a "one pot" suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using (13)C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems.

  2. Systems biology and metabolic engineering of lactic acid bacteria for improved fermented foods

    NARCIS (Netherlands)

    Flahaut, N.A.L.; Vos, de W.M.

    2014-01-01

    Lactic acid bacteria have long been used in industrial dairy and other food fermentations that make use of their metabolic activities leading to products with specific organoleptic properties. Metabolic engineering is a rational approach to steer fermentations toward the production of desired compou

  3. Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis.

    Science.gov (United States)

    Halama, Anna; Horsch, Marion; Kastenmüller, Gabriele; Möller, Gabriele; Kumar, Pankaj; Prehn, Cornelia; Laumen, Helmut; Hauner, Hans; Hrabĕ de Angelis, Martin; Beckers, Johannes; Suhre, Karsten; Adamski, Jerzy

    2016-01-01

    Fat cell metabolism has an impact on body homeostasis and its proper function. Nevertheless, the knowledge about simultaneous metabolic processes, which occur during adipogenesis and in mature adipocytes, is limited. Identification of key metabolic events associated with fat cell metabolism could be beneficial in the field of novel drug development, drug repurposing, as well as for the discovery of patterns predicting obesity risk. The main objective of our work was to provide comprehensive characterization of metabolic processes occurring during adipogenesis and in mature adipocytes. In order to globally determine crucial metabolic pathways involved in fat cell metabolism, metabolomics and transcriptomics approaches were applied. We observed significantly regulated metabolites correlating with significantly regulated genes at different stages of adipogenesis. We identified the synthesis of phosphatidylcholines, the metabolism of even and odd chain fatty acids, as well as the catabolism of branched chain amino acids (BCAA; leucine, isoleucine and valine) as key regulated pathways. Our further analysis led to identification of an enzymatic switch comprising the enzymes Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase) and Auh (AU RNA binding protein/enoyl-CoA hydratase) which connects leucine degradation with cholesterol synthesis. In addition, propionyl-CoA, a product of isoleucine degradation, was identified as a putative substrate for odd chain fatty acid synthesis. The uncovered crosstalks between BCAA and lipid metabolism during adipogenesis might contribute to the understanding of molecular mechanisms of obesity and have potential implications in obesity prediction. PMID:26408941

  4. Engineering Escherichia Coli Fatty Acid Metabolism for the Production of Biofuel Precursors

    OpenAIRE

    Ford, Tyler John

    2015-01-01

    Medium chain fatty acids (MCFAs, 6-12 carbons) are potential precursors to biofuels with properties similar to gasoline and diesel fuel but are not native products of Escherichia coli fatty acid synthesis. Herein we engineer E. coli to produce, metabolize, and activate MCFAs for their future reduction into alcohols and alkanes (potential biofuels). We develop an E. coli strain with an octanoate (8-carbon MCFA) producing enzyme (a thioesterase), metabolic knockouts, and the capa...

  5. HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy

    OpenAIRE

    Lee, Ting-I; Kao, Yu-Hsun; Tsai, Wen-Chin; Chung, Cheng-Chih; Chen, Yao-Chang; Chen, Yi-Jen

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) regulate cardiac glucose and lipid homeostasis. Histone deacetylase (HDAC) inhibitor has anti-inflammatory effects which may play a key role in modulating PPARs and fatty acid metabolism. The aim of this study was to investigate whether HDAC inhibitor, MPT0E014, can modulate myocardial PPARs, inflammation, and fatty acid metabolism in diabetes mellitus (DM) cardiomyopathy. Electrocardiography, echocardiography, and western blotting were used...

  6. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    OpenAIRE

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas; Mattijssen, Frits; Evers-van Gogh, Inkie; Schaart, Gert; Jeppesen, Jacob; Kneppers, Anita; Mensink, Marco; Voshol, Peter J.; Olivecrona, Gunilla; Tan, Nguan Soon; Hesselink, Matthijs K. C.; Berbée, Jimmy F.; Rensen, Patrick C N

    2014-01-01

    Physical exercise causes profound changes in energy metabolism in humans. In this study we show that resting skeletal muscle has a crucial role in the metabolic response to acute exercise. During endurance exercise, selective induction of the protein angiopoietin-like 4 (ANGPTL4) in nonexercising muscle reduces local fatty acid uptake, presumably to prevent fat overload, while directing fatty acids to the active skeletal muscle as fuel. Our data thus suggest that nonexercising muscle has a ke...

  7. The gut microbiota modulates host amino acid and glutathione metabolism in mice

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias;

    2015-01-01

    The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from......, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism...... conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon...

  8. Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C-metabolic flux analysis.

    Science.gov (United States)

    He, Lian; Xiao, Yi; Gebreselassie, Nikodimos; Zhang, Fuzhong; Antoniewiez, Maciek R; Tang, Yinjie J; Peng, Lifeng

    2014-03-01

    We engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull-push-block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions. Metabolic fluxes were determined for the engineered E. coli and its control strain using tracer ([1,2-13C]glucose) experiments and 13C-metabolic flux analysis. Cofactor (NADPH) and energy (ATP) balances were also investigated for both strains based on estimated fluxes. Compared to the control strain, fatty acid overproduction led to significant metabolic responses in the central metabolism: (1) Acetic acid secretion flux decreased 10-fold; (2) Pentose phosphate pathway and Entner–Doudoroff pathway fluxes increased 1.5- and 2.0-fold, respectively; (3) Biomass synthesis flux was reduced 1.9-fold; (4) Anaplerotic phosphoenolpyruvate carboxylation flux decreased 1.7-fold; (5) Transhydrogenation flux converting NADH to NADPH increased by 1.7-fold. Real-time quantitative RT-PCR analysis revealed the engineered strain increased the transcription levels of pntA (encoding the membrane-bound transhydrogenase) by 2.1-fold and udhA (encoding the soluble transhydrogenase) by 1.4-fold, which is in agreement with the increased transhydrogenation flux. Cofactor and energy balances analyses showed that the fatty acid overproducing E. coli consumed significantly higher cellular maintenance energy than the control strain. We discussed the strategies to future strain development and process improvements for fatty acid production in E. coli.

  9. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    Science.gov (United States)

    Xie, Guoxiang; Zhong, Wei; Li, Houkai; Li, Qiong; Qiu, Yunping; Zheng, Xiaojiao; Chen, Huiyuan; Zhao, Xueqing; Zhang, Shucha; Zhou, Zhanxiang; Zeisel, Steven H.; Jia, Wei

    2013-01-01

    Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids in multiple body compartments (liver, gastrointestinal tract, and serum) of rats. Rats were fed a modified Lieber-DeCarli liquid diet with 38% of calories as ethanol (the amount equivalent of 4–5 drinks in humans). While conjugated bile acids predominated in the liver (98.3%), duodenum (97.8%), and ileum (89.7%), unconjugated bile acids comprised the largest proportion of measured bile acids in serum (81.2%), the cecum (97.7%), and the rectum (97.5%). In particular, taurine-conjugated bile acids were significantly decreased in the liver and gastrointestinal tract of ethanol-treated rats, while unconjugated and glycine-conjugated species increased. Ethanol consumption caused increased expression of genes involved in bile acid biosynthesis, efflux transport, and reduced expression of genes regulating bile acid influx transport in the liver. These results provide an improved understanding of the systemic modulations of bile acid metabolism in mammals through the gut-liver axis.—Xie, G., Zhong, W., Li, H., Li, Q., Qiu, Y., Zheng, X., Chen, H., Zhao, X., Zhang, S., Zhou, Z., Zeisel, S. H., Jia, W. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. PMID:23709616

  10. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    OpenAIRE

    Nielsen, Ole H.; Bouchelouche, Pierre N.; Dag Berild

    1992-01-01

    Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l) was as potent as the calcium ionophore A23187 (10 μmol/l) for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the de...

  11. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  12. Fatty Acid Biosynthesis Revisited: Structure Elucidation and Metabolic Engineering

    OpenAIRE

    Beld, Joris; Lee, D. John; Burkart, Michael D.

    2014-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. ...

  13. Hyaluronic acid metabolism is increased in unstable plaques

    NARCIS (Netherlands)

    P.T. Bot; G. Pasterkamp; M.J. Goumans; C. Strijder; F.L. Moll; J.P. de Vries; S.T. Pals; D.P. de Kleijn; J.J. Piek; I.E. Hoefer

    2010-01-01

    P>Background Hyaluronic acid is expressed in atherosclerotic lesions, but its exact role in atherosclerotic disease remains unknown. As degradation of hyaluronic acid by hyaluronidase into low molecular weight hyaluronic acid (LMW-HA) is associated with inflammation and Matrix Metalloproteinase (MMP

  14. Metabolic engineering of Saccharomyces cerevisiae microbial cell factories for succinic acid production

    DEFF Research Database (Denmark)

    Otero, José Manuel; Olsson, Lisbeth; Nielsen, Jens

    2007-01-01

    deletions and over-expression, mutants that overproduce succinic acid have been engineered and thoroughly characterised. Metabolic engineering approaches developed promise to have broad applicability to industrial biotechnology platforms, as well as enhancing fundamental understanding of central carbon...... products is 18, 14, 54, and 9 C-mol/C-mol-glucose, respectively, with biotechnology production is C4 organic acids, encompassing fumaric, malic, and succinic acid. Succinic acid is a key building block molecule...... of systems biology tools to drive C6 carbon flux to succinic acid by enhancement of the two native pathways for succinic acid production: the TCA and glyoxylate cycles. S. cerevisiae does not naturally accumulate succinic acid; however, through the use of in silico metabolic predictions guiding targeted gene...

  15. Occurrence and metabolism of 7-hydroxy-2-indolinone-3-acetic acid in Zea mays

    Science.gov (United States)

    Lewer, P.; Bandurski, R. S.

    1987-01-01

    7-Hydroxy-2-indolinone-3-acetic acid was identified as a catabolite of indole-3-acetic acid in germinating kernels of Zea mays and found to be present in amounts of ca 3.1 nmol/kernel. 7-Hydroxy-2-indolinone-3-acetic acid was shown to be a biosynthetic intermediate between 2-indolinone-3-acetic acid and 7-hydroxy-2-indolinone-3-acetic acid-7'-O-glucoside in both kernels and roots of Zea mays. Further metabolism of 7-hydroxy-2-[5-3H]-indolinone-3-acetic acid-7'-O-glucoside occurred to yield tritiated water plus, as yet, uncharacterized products.

  16. Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: overview and application.

    Science.gov (United States)

    Yoshii, Yukie; Furukawa, Takako; Saga, Tsuneo; Fujibayashi, Yasuhisa

    2015-01-28

    Understanding cancer-specific metabolism is important for identifying novel targets for cancer diagnosis and therapy. Induced acetate/acetyl CoA metabolism is a notable feature that is related to fatty acid synthesis supporting tumor growth. In this review, we focused on the recent findings related to cancer acetate/acetyl CoA metabolism. We also introduce [1-¹¹C]acetate positron emission tomography (PET), which is a useful tool to visualize up-regulation of acetate/acetyl CoA metabolism in cancer, and discuss the utility of [1-¹¹C]acetate PET in cancer diagnosis and its application to personalized medicine.

  17. Hydraulic involute cam actuator

    Science.gov (United States)

    Love, Lonnie J.; Lind, Randall F.

    2011-11-01

    Mechanical joints are provided in which the angle between a first coupled member and a second coupled member may be varied by mechanical actuators. In some embodiments the angle may be varied around a pivot axis in one plane and in some embodiments the angle may be varied around two pivot axes in two orthogonal planes. The joints typically utilize a cam assembly having two lobes with an involute surface. Actuators are configured to push against the lobes to vary the rotation angle between the first and second coupled member.

  18. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

    Directory of Open Access Journals (Sweden)

    Luigi Fontana

    2016-07-01

    Full Text Available Protein-restricted (PR, high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

  19. Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean.

    Directory of Open Access Journals (Sweden)

    Charles Kanobe

    Full Text Available The soybean aphid (Aphis glycines Matsumura is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of "metabolic hijacking" by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor.

  20. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    Science.gov (United States)

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.

  1. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M;

    2016-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohep......The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  2. Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    2015-06-01

    Full Text Available Retinoic acid (RA, an active metabolite of vitamin A (VA, is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs and retinoid X receptors (RXRs. RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor β/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism.

  3. Branched chain amino acids requirements and metabolism in pigs

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham

    2015-01-01

    reasons: first, BCAA share the same enzymes in their catabolic pathways, and there is an interaction among them in a way that excess Leu for example increases the catabolism of them all and changes the requirements. Second, BCAA are not only building blocks of protein biosynthesis, but are also involved......, and Leu requirements in ratio to Lys for pigs after weaning and second, to study the metabolic profile in blood and urine of pigs fed with different BCAA in the diet, and finally, to identify the biomarkers of BCAA, when pigs were fed with the optimum dietary BCAA level to support the best growth...... of the last “-omics”, is a global analysis and interpretation of metabolome in specific health or nutritional status. Non-targeted metabolomics is used for screening the metabolic profile, and the metabolic signature could be used for hypothesis generation. The results of a non-targeted LC-MS metabolomics...

  4. Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study.

    NARCIS (Netherlands)

    Bovenschen, H.J.; Kooijmans-Otero, M.E.; Langewouters, A.M.G.; Vlijmen-Willems, I.M.J.J. van; Rens, D.W.A. van; Seyger, M.M.B.; Kerkhof, P.C.M. van de

    2007-01-01

    BACKGROUND: The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalizatio

  5. Metabolic Effects of Bile Acids in the Gut in Health and Disease

    NARCIS (Netherlands)

    Boesjes, Marije; Brufau Dones, Gemma

    2014-01-01

    In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bil

  6. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett;

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  7. No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

    NARCIS (Netherlands)

    Werner, A; Bongers, MEJ; Bijvelds, MJ; de Jonge, HR; Verkade, HJ

    2004-01-01

    A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes

  8. Microbial transglutaminase production by Streptoverticillium mobaraense: Analysis of amino acid metabolism using mass balances

    NARCIS (Netherlands)

    Zhu, Y.; Rinzema, A.; Bonarius, H.P.J.; Tramper, J.; Bol, J.

    1998-01-01

    Metabolic flows, especially those of amino acids, were determined and analyzed at different stages of a batch fermentation for microbial transglutaminase production by Streptoverticillium mobaraense. The method is mainly based on mass balances and measurements of amino acids and other metabolites. T

  9. Metabolism of fatty acids in rat brain in microsomal membranes

    International Nuclear Information System (INIS)

    Using a technique in which substrate fatty acids are incorporated into microsomal membranes followd by comparison of their rates of desaturation or elongation with those of exogenous added fatty acids it has been found that the desaturation rate is more rapid for the membrane-bound substrate than for the added fatty acid. Moreover, the product of the membrane-bound substrate is incorporated into membrane phospholipid whereas the product of the exogenous substrate is found in di- and triacyl glycerols and in free fatty acids as well. These and other findings point to a normal sequence of reaction of membrane liqids with membrane-bound substrates involving transfer of fatty acid from phospholipid to the coupled enzyme systems without ready equilibration with the free fatty acid pool

  10. Phytanic acid and docosahexaenoic acid increase the metabolism of all-trans-retinoic acid and CYP26 gene expression in intestinal cells.

    Science.gov (United States)

    Lampen, A; Meyer, S; Nau, H

    2001-10-31

    Retinoids are essential for growth and cell differentiation of epithelial tissues. The effects of the food compounds phytol, the phytol metabolite phytanic acid, and the fatty acid docosahexaenoic acid (DHA) on the retinoid signaling pathway in intestinal cells were studied. Phytol inhibited the formation of all-trans-retinoic acid (RA) from dietary retinol in intestinal cells. Phytanic acid, a known retinoic X receptor (RXRalpha) and peroxisome proliferator activating receptor (PPARalpha) activator, also activated PPARdelta, and to a lesser degree PPARgamma, in a transactivation assay. Phytanic acid had no effect on intestinal RA hydroxylase CYP26 (also named P450RAI) gene expression and metabolism of all-trans-RA in intestinal Caco-2 cells. However, in combination with retinoic acid receptor (RAR)-ligands (all-trans-RA or synthetic Am580) phytanic acid enhanced the induction of CYP26 and RA-metabolism in comparison to treatments with all-trans-RA or Am580 alone. Also treatment with DHA did not affect CYP26 gene expression and RA-metabolism but cotreatment of the cells with DHA and all-trans-RA or Am580 enhanced the induction of CYP26, in comparison to the induction caused by all-trans-RA or Am580 alone. This study indicates that food compounds such as phytanic acid and DHA that are RXR-agonists and have an impact on intestinal CYP26 gene expression and metabolism of all-trans-RA in intestinal cells.

  11. Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival.

    Science.gov (United States)

    Fillmore, Natasha; Huqi, Alda; Jaswal, Jagdip S; Mori, Jun; Paulin, Roxane; Haromy, Alois; Onay-Besikci, Arzu; Ionescu, Lavinia; Thébaud, Bernard; Michelakis, Evangelos; Lopaschuk, Gary D

    2015-01-01

    Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo.

  12. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    Directory of Open Access Journals (Sweden)

    Carlotta Lassandro

    2015-08-01

    Full Text Available Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF criteria has been suggested in children. Docosahexaenoic acid (DHA has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  13. AMINO ACID METABOLISM IN COWS DURING THE TRANSITION PERIOD IN BALANCING DIET ON THE EXCHANGE PROTEIN AND DIGESTIBLE AMINO ACIDS

    Directory of Open Access Journals (Sweden)

    Ryadchikov V. G.

    2014-02-01

    Full Text Available Application of a factorial method for determining the needs in metabolic protein and essential amino acids, helps to deepen knowledge on physiology of protein and amino acid supply and allow to improve the standards for dairy cows during the transition period; in insufficient of metabolic protein and essential amino acids increased coefficients of their transformation into net protein and absorptive amino acids as a result of mobilization of body of cows; with an optimal protein nutrition their transformation in net milk protein, lysine and methionine accordingly amounted to 0.67, 0,83 and 0,82. The most significant changes in the concentration of methionine, proline, glutamate, glutamine, glycine were observed in cows before calving and immediately after birth, stabilization of their level starts with a 24 lactation day, that is connected with the peculiarities of the feeding behavior of the cows and the gradual intensification of the processes of metabolism and milk production. To control the status of protein metabolism we have offered benchmarks compositions of free amino acids in cows’ blood plasma phases: 21-0 days before calving, 0-21 and 22-120 days after calving

  14. Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Saltin, B; Wagenmakers, A J

    1999-01-01

    acid production was also 10-fold higher during exercise compared with that at rest (difference not significant). The net production rates of threonine, glycine and tyrosine and of the sum of the non-metabolized amino acids were about 1.5-2.5-fold higher during exercise with the leg with a low glycogen...... in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60......-65% of maximal one-leg power output, starting either with the normal-glycogen or the low-glycogen leg, at random. The net production of threonine, lysine and tyrosine and the sum of the non-metabolized amino acids were 9-20-fold higher (Prest. Total amino...

  15. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats.

    Science.gov (United States)

    Khaire, Amrita; Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2015-08-01

    Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (pomega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.

  16. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder.

    Science.gov (United States)

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Stanford, Kevin E; Hahn, Chang-Gyu; Richtand, Neil M

    2008-09-30

    Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder. PMID:18715653

  17. Organic Acid Metabolism by Isolated Rhizobium japonicum Bacteroids

    Science.gov (United States)

    Stovall, Iris; Cole, Michael

    1978-01-01

    Rhizobium japonicum bacteroids isolated from soybean (Glycine max L.) nodules oxidized 14C-labeled succinate, pyruvate, and acetate in a manner consistent with operation of the tricarboxylic acid cycle and a partial glyoxylate cycle. Substrate carbon was incorporated into all major cellular components (cell wall + membrane, nucleic acids, and protein). PMID:16660386

  18. Physiological and biochemical studies of bacterial amino acid amide metabolism

    NARCIS (Netherlands)

    Hermes, Hubertus Franciscus Maria

    2008-01-01

    Amino acids represent a class of versatile chiral building blocks for a whole range of fine chemicals, used in the pharmaceutical and agro-chemical industry. Considerable experience currently is available with a wide variety of chemo-enzymatic processes for the synthesis of amino acids, which is app

  19. Nitrogen and amino acid metabolism in dairy cows

    NARCIS (Netherlands)

    Tamminga, S.

    1981-01-01

    For the process of milk production, the dairy cow requires nutrients of which energy supplying nutrients and protein or amino acid supplying nutrients are the most important. Amino acid supplying nutrients have to be absorbed from the small intestine and the research reported in this thesis mainly c

  20. Optimisation Methods for Cam Mechanisms

    Directory of Open Access Journals (Sweden)

    Claudia–Mari Popa

    2010-01-01

    Full Text Available In this paper we present the criteria which represent the base of optimizing the cam mechanisms and also we perform the calculations for several types of mechanisms. We study the influence of the constructive parameters in case of the simple machines with rotation cam and follower (flat or curve of translation on the curvature radius and that of the transmission angle. As it follows, we present the optimization calculations of the cam and flat rotation follower mechanisms, as well as the calculations for optimizing the cam mechanisms by circular groove followers’ help. For an easier interpretation of the results, we have visualized the obtained cam in AutoCAD according to the script files generated by a calculation program.

  1. Phytic acid and raffinose series oligosaccharides metabolism in developing chickpea seeds

    OpenAIRE

    Zhawar, Vikramjit Kaur; Kaur, Narinder; Gupta, Anil Kumar

    2011-01-01

    Phytic acid and raffinose series oligosaccharides (RFOs) have anti-nutritional properties where phytic acid chelates minerals and reduces their bioavailability to humans and other animals, and RFOs cause flatulence. Both phytic acid and RFOs cannot be digested by monogastric animals and are released as pollutant-wastes. Efforts are being made to reduce the contents of these factors without affecting the viability of seeds. This will require a thorough understanding of their metabolism in diff...

  2. Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids.

    Science.gov (United States)

    Kondo, Natsuki; Ohno, Yusuke; Yamagata, Maki; Obara, Takashi; Seki, Naoya; Kitamura, Takuya; Naganuma, Tatsuro; Kihara, Akio

    2014-01-01

    The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized. PMID:25345524

  3. Contributions of Cell Metabolism and H+ Diffusion to the Acidic pH of Tumors

    Directory of Open Access Journals (Sweden)

    Paul A. Schornack

    2003-03-01

    Full Text Available The tumor microenvironment is hypoxic and acidic. These conditions have a significant impact on tumor progression and response to therapies. There is strong evidence that tumor hypoxia results from inefficient perfusion due to a chaotic vasculature. Consequently, some tumor regions are well oxygenated and others are hypoxic. It is commonly believed that hypoxic regions are acidic due to a stimulation of glycolysis through hypoxia, yet this is not yet demonstrated. The current study investigates the causes of tumor acidity by determining acid production rates and the mechanism of diffusion for H+ equivalents through model systems. Two breast cancer cell lines were investigated with divergent metabolic profiles: nonmetastatic MCF-7/s and highly metastatic MDA-mb-435 cells. Glycolysis and acid production are inhibited by oxygen in MCF-7/s cells, but not in MDA-mb-435 cells. Tumors of MDAmb-435 cells are significantly more acidic than are tumors of MCF-7/s cells, suggesting that tumor acidity is primarily caused by endogenous metabolism, not the lack of oxygen. Metabolically produced protons are shown to diffuse in association with mobile buffers, in concordance with previous studies. The metabolic and diffusion data were analyzed using a reaction-diffusion model to demonstrate that the consequent pH profiles conform well to measured pH values for tumors of these two cell lines.

  4. Metabolically Engineered Fungal Cells With Increased Content Of Polyunsaturated Fatty Acids

    DEFF Research Database (Denmark)

    2008-01-01

    This invention relates to the production of fatty acids and particularly to the production of the polyunsaturated fatty acids (PUFAs) arachidonic acid (ARA) and eicosapentaenoic acid (EPA) in genetically engineered fungal cells, in particular, to metabolically engineered Saccharomyces cerevisiae...... cells with increased content of ARA and EPA. The invention especially involves improvement of the PUFA content in the host organism through various over-expression of e.g. cytochrome b5 and cytochrome b5 reductase involved in fatty acid desaturation, and heterologous expression of cytochrome b5...

  5. Metabolism of Aromatic Amino Acids during the Growth Cycle of Batch Suspension Cultures of Catharanthus roseus

    OpenAIRE

    Nagaoka, Noriko; ASHIHARA, Hiroshi

    1988-01-01

    Profiles of the levels and metabolism of aromatic compounds in suspension-cultured cells of Catharanthus roseus during the growth cycle were determined. The level of total protein-amino acids, i.e., sum of the amounts of amino acids in hydrolyzates of proteins, and the level of total phenolic acids increased after transfer of the cells in the stationary phase to fresh Murashige-Skoog medium. The maximum levels of the proteinamino acids and those of the phenolic acids were observed on days 3-5...

  6. Effect of salicylic acid on the growth photosynthesis and carbohydrate metabolism in salt stressed maize plants

    International Nuclear Information System (INIS)

    Aqueous solutions of salicylic acid as a spray to Na CI-treated corn (Zea mays L,) significantly increased the growth of shoots and roots as measured after seven days of treatment. Spraying of salicylic acid caused significant increases in the activity of both ribulose 1,5 bisphosphate carboxylase (rubisco) enzyme and photosynthetic pigments. Moreover, salicylic acid treatment induced high values of soluble carbohydrate fractions in salt stressed plants as compared with salicylic acid treated samples. These data suggest that salicylic acid might improve the growth pattern of NaCl-treated maize plants via increasing the rate of photosynthesis and carbohydrate metabolism

  7. Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Eoin Barrett

    Full Text Available The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15 were orally gavaged with either B. breve DPC6330 (10(9 microorganisms/day alone or in combination with 0.5% (w/w linoleic acid & 0.5% (w/w α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11 in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05. Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11 in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05, whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05 compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01 and α-linolenic acid in adipose tissue (p<0.001, whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05, and α-linolenic acid in adipose tissue (p<0.001. B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated

  8. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    Science.gov (United States)

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26683700

  9. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    Science.gov (United States)

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  10. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    Directory of Open Access Journals (Sweden)

    Ole H. Nielsen

    1992-01-01

    Full Text Available Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l was as potent as the calcium ionophore A23187 (10 μmol/l for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the decreases in radioactivity by 15.4% and 30.5%, respectively. The mechanism responsible for the release of arachidonate from cellular membranes is closely coupled to cellular calcium metabolism, and melittin was found to promote calcium entry through receptor gated calcium channels, probably due to an activation of phospholipase A2. Furthermore, a down-regulation of leukotriene B4 receptors was seen. The maximal number of binding sites per cell was reduced from a median of 1520 to 950 with melittin (1 μmol/l. The study has revealed some factors important for the inflammatory mechanisms mediated by melittin.

  11. Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis.

    OpenAIRE

    Guichardant, Michel; Calzada, Catherine; Bernoud-Hubac, Nathalie; Lagarde, Michel; Véricel, Evelyne

    2014-01-01

    International audience; Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoprote...

  12. Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism.

    Science.gov (United States)

    Ma, Yu; Bao, Yongrui; Wang, Shuai; Li, Tianjiao; Chang, Xin; Yang, Guanlin; Meng, Xiansheng

    2016-08-01

    Inflammation is an important immune response; however, excessive inflammation causes severe tissue damages and secondary inflammatory injuries. The long-term and ongoing uses of routinely used drugs such as non-steroidal anti-inflammatory drugs (NSAIDS) are associated with serious adverse reactions, and not all patients have a well response to them. Consequently, therapeutic products with more safer and less adverse reaction are constantly being sought. Radix Bupleuri, a well-known traditional Chinese medicine (TCM), has been reported to have anti-inflammatory effects. However, saikosaponins (SS) as the main pharmacodynamic active ingredient, their pharmacological effects and action mechanism in anti-inflammation have not been reported frequently. This study aimed to explore the anti-inflammatory activity of SS and clarify the potential mechanism in acute inflammatory mice induced by subcutaneous injection of formalin in hind paws. Paw edema was detected as an index to evaluate the anti-inflammatory efficacy of SS. Then, a metabolomic method was used to investigate the changed metabolites and potential mechanism of SS. Metabolite profiling was performed by high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The detection and identification of the changed metabolites were systematically analyzed by multivariate data and pathway analysis. As a result, 12 different potential biomarkers associated with SS in anti-inflammation were identified, including nicotinate, niacinamide, arachidonic acid (AA), and 20-carboxy-leukotriene B4, which are associated with nicotinate and nicotinamide metabolism and arachidonic acid metabolism. The expression levels of biomarkers were effectively modulated towards the normal range by SS. It indicated that SS show their effective anti-inflammatory effects through regulating nicotinate and nicotinamide metabolism and arachidonic acid metabolism. PMID:27251379

  13. Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria

    Institute of Scientific and Technical Information of China (English)

    Purnima Guda; Chittibabu Guda; Shankar Subramaniam

    2007-01-01

    We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochon- dria. Human mitochondrial proteins determined by experimental and computa- tional methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mito- chondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which pre- dicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we recon- structed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.

  14. Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia.

    Science.gov (United States)

    Siekmeyer, Manuela; Petzold-Quinque, Stefanie; Terpe, Friederike; Beblo, Skadi; Gebhardt, Rolf; Schlensog-Schuster, Franziska; Kiess, Wieland; Siekmeyer, Werner

    2013-01-01

    The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism.

  15. Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis

    NARCIS (Netherlands)

    Hoefnagel, M.H.N.; Starrenburg, M.J.C.; Martens, D.E.; Hugenholtz, J.; Kleerenbezem, M.; Swam, van I.; Bongers, R.

    2002-01-01

    Everyone who has ever tried to radically change metabolic fluxes knows that it is often harder to determine which enzymes have to be modified than it is to actually implement these changes. In the more traditional genetic engineering approaches ’bottle-necks’ are pinpointed using qualitative, intuit

  16. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Hao, Qin; Jørgensen, Henry Johs. Høgh;

    2011-01-01

    with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1a, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited...

  17. Synthesis and Metabolism of Carbonyl-C14 Pyruvic andHydroxypyruvic Acids in Algae

    Energy Technology Data Exchange (ETDEWEB)

    Milhaud, Gerhard; Benson, Andrew A.; Calvin, M.

    1955-03-30

    1. Pyruvic and hydroxypyruvic acids a r e metabolized by Scenedesmus. 2. The products of metabolism of pyruvic -2 -C{sup 14} and hydroxypyruvic-2 -C{sup 14} acids a r e essentially identical to those of C{sup 14}-O fixations. 3. Lipids a r e rapidly formed i n the light from both substrates. In the dark the major products a r e intermediates of the tricarboxylic acid cycle. 4. Zt does not appear likely that f r e e hydroxypyruvic acid is a photosynthetic intermediate, 5 . Tricarboxylic acid cycle intermediates a r e formed from exogenous pyruvate a s fast in the light a s in the dark.

  18. Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis

    OpenAIRE

    Yasunori Konno; Shigeharu Ueki; Masahide Takeda; Yoshiki Kobayashi; Mami Tamaki; Yuki Moritoki; Hajime Oyamada; Masamichi Itoga; Hiroyuki Kayaba; Ayumi Omokawa; Makoto Hirokawa

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR1...

  19. Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis

    OpenAIRE

    Shriver, Leah P.; Manchester, Marianne

    2011-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and a leading cause of neurological disability. The complex immunopathology and variable disease course of multiple sclerosis have limited effective treatment of all patients. Altering the metabolism of immune cells may be an attractive strategy to modify their function during autoimmunity. We examined the effect of inhibiting fatty acid metabolism in experimental autoimmune encephalomyelitis (EAE), a mo...

  20. Fatty acids from diet and microbiota regulate energy metabolism [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Joe Alcock

    2015-09-01

    Full Text Available A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

  1. Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chao; Cao, Yujin; Zou, Huibin; Xian, Mo [Chinese Academy of Sciences, Qingdao (China). Key Lab. of Biofuels

    2011-02-15

    Confronted with the gradual and inescapable exhaustion of the earth's fossil energy resources, the bio-based process to produce platform chemicals from renewable carbohydrates is attracting growing interest. Escherichia coli has been chosen as a workhouse for the production of many valuable chemicals due to its clear genetic background, convenient to be genetically modified and good growth properties with low nutrient requirements. Rational strain development of E. coli achieved by metabolic engineering strategies has provided new processes for efficiently biotechnological production of various high-value chemical building blocks. Compared to previous reviews, this review focuses on recent advances in metabolic engineering of the industrial model bacteria E. coli that lead to efficient recombinant biocatalysts for the production of high-value organic acids like succinic acid, lactic acid, 3-hydroxypropanoic acid and glucaric acid as well as alcohols like 1,3-propanediol, xylitol, mannitol, and glycerol with the discussion of the future research in this area. Besides, this review also discusses several platform chemicals, including fumaric acid, aspartic acid, glutamic acid, sorbitol, itaconic acid, and 2,5-furan dicarboxylic acid, which have not been produced by E. coli until now. (orig.)

  2. Influence of organic acids and organochlorinated insecticides on metabolism of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Pejin Dušanka J.

    2005-01-01

    Full Text Available Saccharomyces cerevisiae is exposed to different stress factors during the production: osmotic, temperature, oxidative. The response to these stresses is the adaptive mechanism of cells. The raw materials Saccharomyces cerevisiae is produced from, contain metabolism products of present microorganisms and protective agents used during the growth of sugar beet for example the influence of acetic and butyric acid and organochlorinated insecticides, lindan and heptachlor, on the metabolism of Saccharomyces cerevisiae was investigated and presented in this work. The mentioned compounds affect negatively the specific growth rate, yield, content of proteins, phosphorus, total ribonucleic acids. These compounds influence the increase of trechalose and glycogen content in the Saccharomyces cerevisiae cells.

  3. Myocardial fatty acid metabolism and lipotoxicity in the setting of insulin resistance.

    Science.gov (United States)

    Kok, Bernard P C; Brindley, David N

    2012-10-01

    Management of diabetes and insulin resistance in the setting of cardiovascular disease has become an important issue in an increasingly obese society. Besides the development of hypertension and buildup of atherosclerotic plaques, the derangement of fatty acid and lipid metabolism in the heart plays an important role in promoting cardiac dysfunction and oxidative stress. This review discusses the mechanisms by which metabolic inflexibility in the use of fatty acids as the preferred cardiac substrate in diabetes produces detrimental effects on mechanical efficiency, mitochondrial function, and recovery from ischemia. Lipid accumulation and the consequences of toxic lipid metabolites are also discussed. PMID:22999246

  4. Studies of citric acid metabolism in heart muscle

    NARCIS (Netherlands)

    Meduski, J.W.

    1950-01-01

    1. The pentabromoacetone method for the determination of citric acid was studied; a modification of the procedure of Natelson, Lugovoy and Pincus was used. 2. Two tissue preparations were obtained. The first by washing with water, the second by washing with water and then with 0.5% sodium bicarbo

  5. Neridronic acid for the treatment of bone metabolic diseases.

    Science.gov (United States)

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Adami, Silvano

    2009-10-01

    Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns ( 75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance. PMID:19761412

  6. Engineering the fatty acid metabolic pathway in Saccharomyces cerevisiae for advanced biofuel production

    Directory of Open Access Journals (Sweden)

    Xiaoling Tang

    2015-12-01

    Full Text Available Fatty acid-derived fuels and chemicals have attracted a great deal of attention in recent decades, due to their following properties of high compatibility to gasoline-based fuels and existing infrastructure for their direct utilization, storage and distribution. The yeast Saccharomyces cerevisiae is the ideal biofuel producing candidate, based on the wealth of available genetic information and versatile tools designed to manipulate its metabolic pathways. Engineering the fatty acid metabolic pathways in S. cerevisiae is an effective strategy to increase its fatty acid biosynthesis and provide more pathway precursors for production of targeted products. This review summarizes the recent progress in metabolic engineering of yeast cells for fatty acids and fatty acid derivatives production, including the regulation of acetyl-CoA biosynthesis, NADPH production, fatty acid elongation, and the accumulation of activated precursors of fatty acids for converting enzymes. By introducing specific enzymes in the engineered strains, a powerful platform with a scalable, controllable and economic route for advanced biofuel production has been established.

  7. Investigations into selective metabolic aspects of bifidobacteria: carbohydrate metabolism, fatty acid biosynthesis and plasmid biology

    OpenAIRE

    O'Connell, Kerry Joan

    2014-01-01

    The gastrointestinal tract (GIT) is a diverse ecosystem, and is colonised by a diverse array of bacteria, of which bifidobacteria are a significant component. Bifidobacteria are Gram-positive, saccharolytic, non-motile, non-sporulating, anaerobic, Y-shaped bacteria, which possess a high GC genome content. Certain bifidobacteria possess the ability to produce conjugated linoleic acid (CLA) from linoleic acid (LA) by a biochemical pathway that is hypothesised to be achieved via a linoleic isome...

  8. Metabollic Engineering of Saccharomyces Cereviae a,omi acid metabolism for production of products of industrial interest

    DEFF Research Database (Denmark)

    Chen, Xiao

    -based processes. This study has focused on metabolic engineering of the amino acid metabolism in S. cerevisiae for production of two types of chemicals of industrial interest. The first chemical is δ-(L-α-aminoadipyl)–L-cysteinyl–D-valine (LLD-ACV). ACV belongs to non-ribosomal peptides (NRPs), which...... of one type of NRPs – ACV. Production of ACV was achieved by introducing the Penicillium chrysogenum gene pcbAB, which encodes ACV synthetase (ACVS), and the Aspergillus nidulans gene npgA, which encodes phosphopantetheinyl transferase (PPTase) required for activation of ACVS, into S. cerevisiae...... on a high-copy plasmid. Several possible factors that could improve ACV production were investigated. Lowering the cultivation temperature from 30 to 20 oC led to a 30-fold enhancement. The ACVS and PPTase encoding genes were also integrated into the yeast genome. The second chemical is isobutanol, which...

  9. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    DEFF Research Database (Denmark)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner;

    2016-01-01

    OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related t...... catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D....... methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. RESULTS: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate...... fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. CONCLUSIONS: Our data indicate that impaired muscle BCAA...

  10. Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

    Science.gov (United States)

    Vangaveti, Venkat N; Jansen, Holger; Kennedy, Richard Lee; Malabu, Usman H

    2016-08-15

    Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo

  11. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Yukino Hatazawa

    Full Text Available Peroxisome proliferator-activated receptor (PPAR γ coactivator 1α (PGC-1α is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT 2, branched-chain α-keto acid dehydrogenase (BCKDH, which catabolize BCAA. The expression of BCKDH kinase (BCKDK, which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  12. Metabolic engineering of chloroplasts for artemisinic acid biosynthesis and impact on plant growth

    Indian Academy of Sciences (India)

    Bhawna Saxena; Mayavan Subramaniyan; Karan Malhotra; Neel Sarovar Bhavesh; Shobha Devi Potlakayala; Shashi Kumar

    2014-03-01

    Chloroplasts offer high-level transgene expression and transgene containment due to maternal inheritance, and are ideal hosts for biopharmaceutical biosynthesis via multigene engineering. To exploit these advantages, we have expressed 12 enzymes in chloroplasts for the biosynthesis of artemisinic acid (precursor of artemisinin, antimalarial drug) in an alternative plant system. Integration of transgenes into the tobacco chloroplast genome via homologous recombination was confirmed by molecular analysis, and biosynthesis of artemisinic acid in plant leaf tissues was detected with the help of 13C NMR and ESI-mass spectrometry. The excess metabolic flux of isopentenyl pyrophosphate generated by an engineered mevalonate pathway was diverted for the biosynthesis of artemisinic acid. However, expression of megatransgenes impacted the growth of the transplastomic plantlets. By combining two exogenous pathways, artemisinic acid was produced in transplastomic plants, which can be improved further using better metabolic engineering strategies for commercially viable yield of desirable isoprenoid products.

  13. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana;

    2014-01-01

    in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.......i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma...

  14. New insights into the regulation of plant immunity by amino acid metabolic pathways.

    Science.gov (United States)

    Zeier, Jürgen

    2013-12-01

    Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity.

  15. Metabolism of nonparticulate phosphorus in an acid bog lake

    Energy Technology Data Exchange (ETDEWEB)

    Koenings, J. P.

    1977-01-01

    In North Gate Lake, an acid bog lake located on the northern Michigan-Wisconsin border, U.S.A., the algal nutrient inorganic phosphate (FRP) is not detectable by chemical means. Organic phosphorus (FUP) represents 100% of the detectable filterable phosphorus. The availability and cycling of this organic fraction are of considerable interest in regard to the primary productivity of this system. To clarify these relationships, the cycling of nonparticulate forms of phosphorus found in the epilimnion of this lake was studied.

  16. Metabolism of nonparticulate phosphorus in an acid bog lake

    International Nuclear Information System (INIS)

    In North Gate Lake, an acid bog lake located on the northern Michigan-Wisconsin border, U.S.A., the algal nutrient inorganic phosphate (FRP) is not detectable by chemical means. Organic phosphorus (FUP) represents 100% of the detectable filterable phosphorus. The availability and cycling of this organic fraction are of considerable interest in regard to the primary productivity of this system. To clarify these relationships, the cycling of nonparticulate forms of phosphorus found in the epilimnion of this lake was studied

  17. Metabolic regulation of amino acid uptake in marine waters

    Energy Technology Data Exchange (ETDEWEB)

    Kirchman, D.L.; Hodson, R.E.

    1986-03-01

    To determine the relationships among the processes of uptake, intracellular pool formation, and incorporation of amino acids into protein, the authors measured the uptake of dipeptides and free amino acids by bacterial assemblages in estuarine and coastal waters of the southeast US. The dipeptide phenylalanyl-phenylalanine (phe-phe) lowered V/sub max/ of phenylalanine uptake when the turnover rate of phenylalanine was relatively high. When the turnover rate was relatively low, phe-phe either had no effect or increased V/sub max/ of phenylalanine uptake. An analytical model was developed and tested to measure the turnover time of the intracellular pool of phenylalanine. The results suggested that the size of the intracellular pool is regulated, which precludes high assimilation rates of both phenylalanine and phe-phe. In waters with relatively low phenylalanine turnover rates, bacterial assemblages appear to have a greater capacity to assimilate phenylalanine and phe-phe simultaneously. Marine bacterial assemblages do not substantially increase the apparent respiration of amino acids when concentrations increase. The authors conclude that sustained increases in uptake rates and mineralization by marine bacterial assemblages in response to an increase in the concentrations of dissolved organic nitrogen is determined by the rate of protein synthesis.

  18. Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways

    OpenAIRE

    Gomes, Ana; Fernandes, Eduarda; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Lima, José Costa

    2009-01-01

    Abstract Cyclooxygenases (COXs) are the key enzymes in the biosynthesis of prostanoids. COX-1 is a constitutive enzyme while the expression of COX-2 is highly stimulated in the event of inflammatory processes, leading to the production of large amounts of prostaglandins (PGs), in particular PGE2 and PGI2, which are pro-inflammatory mediators. Lipoxygenases (LOXs) are enzymes that produce hydroxy acids and leukotrienes (LTs). 5-LOX metabolizes arachidonic acid to yield, a...

  19. Abnormal Unsaturated Fatty Acid Metabolism in Cystic Fibrosis: Biochemical Mechanisms and Clinical Implications

    OpenAIRE

    Seegmiller, Adam C.

    2014-01-01

    Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely increased expression and activity of fatty acid desaturases. Among other effects, this drives metabolism of linoeate to arachidonate. Increased desaturase expression appears to be ...

  20. TRANSLATIONAL STUDIES ON REGULATION OF BRAIN DOCOSAHEXAENOIC ACID (DHA) METABOLISM IN VIVO

    OpenAIRE

    Rapoport, Stanley I.

    2012-01-01

    One goal in the field of brain polyunsaturated fatty acid (PUFA) metabolism is to translate the many studies that have been conducted in vitro and in animal models to the clinical setting. Doing so should elucidate the role of PUFAs in the human brain, and effects of diet, drugs, disease and genetics. This review briefly discusses new in vivo radiotracer kinetic and neuroimaging techniques that allow us to do this, with a focus on docosahexaenoic acid (DHA). We illustrate how brain PUFA metab...

  1. Liarozole, an Inhibitor of Retinoic Acid Metabolism, Retarded Atherogenesis in LDLR-/- Mice

    OpenAIRE

    Zolberg Relevy, Noa; Harari, Ayelet; Kamari, Yehuda; Harats, Dror; Shaish, Aviv

    2015-01-01

    Liarozole is a Retinoic Acid Metabolism Blocking Agent (RAMBA). As retinoic acid (RA) and its precursor, beta-carotene (BC), have been shown to inhibit atherosclerosis development in mouse models, in the present study we investigated whether liarozole can mimic the anti-atherogenic effect of RA. We demonstrate, by using the LDL receptor-knockout mouse model fed a high-fat diet, that liarozole significantly reduces by 50% the aortic sinus atherosclerotic lesion area.    

  2. Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution.

    Science.gov (United States)

    Liu, Jianguo; Wang, Qunhui; Zou, Hui; Liu, Yingying; Wang, Juan; Gan, Kemin; Xiang, Juan

    2013-11-01

    The (13) C isotope tracer method was used to investigate the glucose metabolic flux distribution and regulation in Lactobacillus amylophilus to improve lactic acid production using kitchen waste saccharified solution (KWSS). The results demonstrate that L. amylophilus is a homofermentative bacterium. In synthetic medium, 60.6% of the glucose entered the Embden-Meyerhof-Parnas (EMP) to produce lactic acid, whereas 36.4% of the glucose entered the pentose phosphate metabolic pathway (HMP). After solid-liquid separation of the KWSS, the addition of Fe(3+) during fermentation enhanced the NADPH production efficiency and increased the NADH content. The flux to the EMP was also effectively increased. Compared with the control (60.6% flux to EMP without Fe(3+) addition), the flux to the EMP with the addition of Fe(3+) (74.3%) increased by 23.8%. In the subsequent pyruvate metabolism, Fe(3+) also increased lactate dehydrogenase activity, and inhibited alcohol dehydrogenase, pyruvate dehydrogenase and pyruvate carboxylase, thereby increasing the lactic acid production to 9.03 g l(-1) , an increase of 8% compared with the control. All other organic acid by-products were lower than in the control. However, the addition of Zn(2+) showed an opposite effect, decreasing the lactic acid production. In conclusion it is feasible and effective means using GC-MS, isotope experiment and MATLAB software to integrate research the metabolic flux distribution of lactic acid bacteria, and the results provide the theoretical foundation for similar metabolic flux distribution. PMID:23489617

  3. Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum.

    Science.gov (United States)

    Amador-Noguez, Daniel; Feng, Xiao-Jiang; Fan, Jing; Roquet, Nathaniel; Rabitz, Herschel; Rabinowitz, Joshua D

    2010-09-01

    Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways of Clostridium acetobutylicum, a soil bacterium whose major fermentation products include the biofuels butanol and hydrogen. While genome annotation suggests the absence of most tricarboxylic acid (TCA) cycle enzymes, our results demonstrate that this bacterium has a complete, albeit bifurcated, TCA cycle; oxaloacetate flows to succinate both through citrate/alpha-ketoglutarate and via malate/fumarate. Our investigations also yielded insights into the pathways utilized for glucose catabolism and amino acid biosynthesis and revealed that the organism's one-carbon metabolism is distinct from that of model microbes, involving reversible pyruvate decarboxylation and the use of pyruvate as the one-carbon donor for biosynthetic reactions. This study represents the first in vivo characterization of the TCA cycle and central metabolism of C. acetobutylicum. Our results establish a role for the full TCA cycle in an obligatory anaerobic organism and demonstrate the importance of complementing genome annotation with isotope tracer studies for determining the metabolic pathways of diverse microbes.

  4. Effects of the oestrous cycle on the metabolism of arachidonic acid in rat isolated lung.

    Science.gov (United States)

    Bakhle, Y S; Zakrzewski, J T

    1982-01-01

    1. The metabolism of exogenous arachidonic acid perfused through the pulmonary circulation was investigated in lungs taken from rats at different stages of the oestrous cycle. 2. Following perfusion with [14C]arachidonic acid there was more radioactivity associated with cyclo-oxygenase products in general at pro-oestrus than at any other stage of the cycle. 3. Production of 6-oxo-prostaglandin F1 alpha and hence of prostacyclin (PGI2) was also highest at pro-oestrus. 4. Production of thromboxane B2 was highest at pro-oestrus although it was never greater than PGI2 production at any stage. 5. Radioactivity retained in lung tissue was mostly present in phospholipid and free fatty acid fractions with the distribution at pro-oestrus being different from the other stages. 6. Following perfusion with [14C]oleic acid (which is not a substrate for cyclooxygenase), variations in the distribution of label in radioactivity in lung were also observed. However, these were not related to the stages of the oestrous cycle in the same way as those associated with arachidonic acid. 7. We conclude that both pathways of arachidonic acid metabolism in lung--oxidation via cyclo-oxygenase and incorporation into phospholipid - are affected by the progress of the oestrous cycle. 8. Altered arachidonate metabolism appeared to be associated chiefly with pro-oestrus and may be linked to those hormones involved in this stage of the oestrous cycle. PMID:6809935

  5. Quantitatively metabolic profiles of salvianolic acids in rats after gastric-administration of Salvia miltiorrhiza extract.

    Science.gov (United States)

    Liu, Zhanli; Zheng, Xunyang; Guo, Yanlei; Qin, Weihan; Hua, Lei; Yang, Yong

    2016-09-01

    Salvianolic acids, the well-known active components in Salvia miltiorrhiza, have been shown to possess markedly pharmacological activities. However, due to the complex in vivo course after administration, the pharmacologically active forms are still poorly understood. In present study, we evaluated the stability of eight major salvianolic acids from Danshen extract under different chemical and physiological conditions. We also quantitatively explained the absorption, metabolism and excretion of these salvianolic acids in rats after gastric-administration, which was carried out by simultaneously determining the amounts of salvianolic acids and their metabolites in the rat gastrointestinal contents, gastrointestinal mucosa, plasma, bile and urine. We found that: 1) protocatechuic aldehyde (PAL) was much stable whether in acidic environment (pH4.0) or in alkaline environment (pH8.0), while other salvianolic acids were stable in acidic environment and instable in alkaline environment; 2) PAL, salvianoli acid A (SAA) and salvianolic acid B (SAB) were instable whether in rat stomach or in small intestine, while other salvianolic acids were stable in rat stomach and instable in small intestine; 3) after gastric-administration, except PAL and Danshensu (DSS), other phenolic acids would be metabolized into DSS and caffeic acid (CA) in the rat gastrointestinal tract before absorption, and only free and glucuronidated PAL, CA and DSS were detected in rat plasma, bile and urine. In conclusion, it was the free and glucuronidated PAL, CA and DSS rather than the prototypes of other salvianolic acids that were present in plasma with considerable concentrations after gastric-administration. PMID:27370098

  6. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  7. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-07-26

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis.

  8. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-01-01

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis. PMID:27455877

  9. Urine acidification and mineral metabolism in growing pigs feddiets supplemented with dietary methionine and benzoic acid

    DEFF Research Database (Denmark)

    Nørgaard, Jan Værum; Fernández, José Adalberto; Eriksen, Jørgen;

    2010-01-01

    Benzoic acid (BA) reduces pH of urine and thereby reduces the emission of ammonia and possibly also odorous sulphur-compounds from slurry. The effect of BA on mineral metabolism in growing pigs is not clear. The objective was therefore to study the effect of BA and methionine (Met) as a sulphur (S...

  10. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression

    NARCIS (Netherlands)

    Mocking, Roel J T; Ruhe, Eric; Assies, Johanna; Lok, Anja; Koeter, Maarten W J; Visser, Ieke; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity and fatty acid (FA)-metabolism have been observed in (recurrent) major depressive disorder (MDD). Through the pathophysiological roles of FAs in the brain and cardiovascular system, a hypothesized relationship between HPA-axis activit

  11. A dynamic mechanistic model of lactic acid metabolism in the rumen

    NARCIS (Netherlands)

    Mills, J.A.N.; Crompton, L.A.; Ellis, J.L.; Dijkstra, J.; Bannink, A.; Hook, S.E.; Benchaar, C.; France, J.

    2014-01-01

    Current feed evaluation systems for ruminants are too imprecise to describe diets in terms of their acidosis risk. The dynamic mechanistic model described herein arises from the integration of a lactic acid (La) metabolism module into an extant model of whole-rumen function. The model was evaluated

  12. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Knudsen, Karen Birgitte Moos; Kondrup, Jens;

    2001-01-01

    BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine...

  13. Role of Free Fatty Acid Receptor 2 (FFAR2) in the Regulation of Metabolic Homeostasis.

    Science.gov (United States)

    Mohammad, Sameer

    2015-01-01

    Besides being an important source of fuel and structural components of biological membranes, free fatty acids (FFAs) are known to display a wide variety of roles that include modulation of receptor signaling and regulation of gene expression among many. FFAs play a significant role in maintaining metabolic homeostasis by activating specific G-Protein Coupled Receptors (GPCRs) in pancreatic β cells, immune cells, white adipose tissue, intestine and several other tissues. Free Fatty acid receptor 2 (FFAR2) also known as GPR43 belongs to this group of GPCRs and has been shown to participate in a number of important biological activities. FFAR2 is activated by short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate. SCFAs are formed in the distal gut by bacterial fermentation of macro-fibrous material that escapes digestion in the upper gastrointestinal tract and enters the colon and have been shown to play vital role in the immune regulation and metabolic homeostasis. FFAR2 and other free fatty acid receptors are considered key components of the body's nutrient sensing mechanism and targeting these receptors is assumed to offer novel therapies for the management of diabetes and other metabolic disorders. This review aims to summarize the current state of our understanding of FFAR2 biology with a particular focus on its role in metabolic homeostasis. PMID:25850624

  14. Inhibition of aconitase in citrus fruit callus results in a metabolic shift towards amino acid biosynthesis

    NARCIS (Netherlands)

    Degu, A.; Hatew, B.; Nunes-Nesi, A.; Shlizerman, L.; Zur, N.; Fernie, A.R.; Blumwald, E.; Sadka, A.

    2011-01-01

    Citrate, a major determinant of citrus fruit quality, accumulates early in fruit development and declines towards maturation. The isomerization of citrate to isocitrate, catalyzed by aconitase is a key step in acid metabolism. Inhibition of mitochondrial aconitase activity early in fruit development

  15. Effect of acute metabolic acid/base shifts on the human airway calibre.

    NARCIS (Netherlands)

    Brijker, F.; Elshout, F.J.J. van den; Heijdra, Y.F.; Bosch, F.H.; Folgering, H.T.M.

    2001-01-01

    Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined b

  16. UPTAKE AND METABOLISM OF ALL-TRANS RETINOIC ACID BY THREE NATIVE NORTH AMERICAN RANIDS

    Science.gov (United States)

    Retinoids, which are Vvitamin A derivatives, are important signaling molecules that regulate processes critical for development in all vertebrates. The objective of our study was to examine uptake and metabolism of the model retinoid, all-trans retinoic acid (all-trans RA), by th...

  17. Change of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism

    Institute of Scientific and Technical Information of China (English)

    Hua-Ling Ruan; Li Zhao; Kun-Quan Guo; Kun Yang; Lin-Xiu Ye; Xue Sun

    2016-01-01

    Objective:To study the change situation of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism.Methods:Eighty-one patients with hyperthyroidism who were treated in our hospital from May 2013 to October 2014 were selected as the observation group, while 81 healthy persons with health examination at the same period were the control group. Then, the serum oxygen free radical indexes and free amino acids of the two groups were respectively detected and compared, and the detection results of patients in the observation group with different etiologic types and basal metabolic rate were also compared. Results:The serum oxygen free radical related indexes of the observation group were all higher than those of the control group; the serum antioxidant related indexes were all lower than those of the control group; and the serum free amino acids levels were all obviously lower than those of the control group. Besides, the detection results of patients with severe hyperthyroidism in the observation group were worse than those of patients with mild and moderate disease, while the detection results of the observation group with different types of hyperthyroidism had no significant differences.Conclusions:The fluctuation of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism are obvious, and the detection results of patients with different basal metabolic rates are also quite obvious.

  18. Endogenous surfactant metabolism in critically ill infants measured with stable isotope labeled fatty acids

    NARCIS (Netherlands)

    Cogo, PE; Carnielli, VP; Bunt, JEH; Badon, T; Giordano, G; Zacchello, F; Sauer, PJJ; Zimmermann, LJI

    1999-01-01

    Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids.

  19. Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology.

    Science.gov (United States)

    Pedersen, Martin B; Gaudu, Philippe; Lechardeur, Delphine; Petit, Marie-Agnès; Gruss, Alexandra

    2012-01-01

    The lactic acid bacteria (LAB) are essential for food fermentations and their impact on gut physiology and health is under active exploration. In addition to their well-studied fermentation metabolism, many species belonging to this heterogeneous group are genetically equipped for respiration metabolism. In LAB, respiration is activated by exogenous heme, and for some species, heme and menaquinone. Respiration metabolism increases growth yield and improves fitness. In this review, we aim to present the basics of respiration metabolism in LAB, its genetic requirements, and the dramatic physiological changes it engenders. We address the question of how LAB acquired the genetic equipment for respiration. We present at length how respiration can be used advantageously in an industrial setting, both in the context of food-related technologies and in novel potential applications.

  20. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    Science.gov (United States)

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes. PMID:25966259

  1. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    Science.gov (United States)

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes.

  2. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  3. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut

    Science.gov (United States)

    Ridlon, Jason M.; Kang, Dae-Joong; Hylemon, Phillip B.; Bajaj, Jasmohan S

    2015-01-01

    The understanding of the complex role of the bile acid-gut microbiome axis in health and disease processes is evolving rapidly. Our focus revolves around the interaction of the gut microbiota with liver diseases, especially cirrhosis. The bile acid pool size has recently been shown to be a function of microbial metabolism of bile acid and regulation of the microbiota by bile acids is important in the development and progression of several liver diseases. Humans produce a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of FXR in intestine and liver. Microbes use bile acids, and via FXR signaling this results in a smaller, unconjugated hydrophobic bile acid pool. This equilibrium is critical to maintain health. The challenge is to examine the manifold functions of gut bile acids as modulators of antibiotic, probiotic and disease progression in cirrhosis, metabolic syndrome and alcohol use. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. With advancing liver disease and cirrhosis, there is dysbiosis in the fecal, ileal and colonic mucosa, in addition to a decrease in bile acid concentration in the intestine due to the liver problems. This results in a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of deoxycholic acid (DCA). Alcohol intake speeds up these processes in the subjects with and without cirrhosis without significant FXR feedback. Taken together, these pathways can impact intestinal and systemic inflammation while worsening dysbiosis. The interaction between bile acids, alcohol, cirrhosis and dysbiosis is an important relationship that influences intestinal and systemic inflammation, which in turn determines progression of the overall disease process. These interactions and the impact of commonly used therapies for liver disease can provide insight into the pathogenesis

  4. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites

    OpenAIRE

    Cooper, George; Reed, Chris; Nguyen,Dang; Carter, Malika; Wang, Yi

    2011-01-01

    Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact ...

  5. Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition

    Directory of Open Access Journals (Sweden)

    Malaisse WJ

    2008-12-01

    Full Text Available Abstract Background There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA depletion on hepatic metabolism. Results n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPARγ, and an increased β-oxidation (CPT1, PPARα and PGC1α without modification of fatty acid esterification (DGAT2, GPAT1, secretion (MTTP or intracellular transport (L-FABP. Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. Conclusion n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between β-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

  6. Radioiodinated PHIPA`s; metabolically trapped fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhut, M. [Heidelberg Univ. (Germany). Radiopharmaceutical Chemistry Lab.

    1998-12-31

    Radioiodinated PHIPA 3-10 [13-(4`-iodophenyl)-3-(p-phenylene)tridecanoic acid] has been developed for nuclear-cardiological investigation of coronary artery disease or cardiomyopathies of various origin. The compound features a phenylene group located within the backbone of a long-chain fatty acid. In spite of its bulky structure [{sup 123}I]PHIPA 3-10 is extracted by the myocardium in a manner similar to that for the unmodified fatty acid analogue, [{sup 123}I]IPPA. The retention of PHIPA 3-10 in heart muscle results from the presence of the p-phenylene group which prevents more than one {beta}-oxidation cycle. Only one single, rapidly formed metabolite was found in rat-heart extracts. According to comparative HPLC with synthetic metabolites and mass spectrometric analysis this metabolite was identified as [{sup 123}I]PHIPA 1-10, a by two methylene groups shortened PHIPA derivative. Formation of this metabolite could be suppressed by Etomoxir, a carnitine palmitoyl fransferase I inhibitor, indicating {beta}-oxidation of [{sup 123}I]PHIPA 3-10 in mitochondria. Final evidence for the involvement of mitochondria in the degradation of [{sup 123}I]PHIPA 3-10 was obtained performing density-gradient centrifugation with homogenized rat heart tissue. Labeled free PHIPA 3-10 and free metabolite peaked with the fraction containing mitochondria. With respect to its biochemical characteristics, [{sup 123}I]PHIPA 3-10 may be considered as a useful tool for nuclear cardiological investigations. (orig.) [Deutsch] Radioiodierte PHIPA 3-10 [13-(4`-Iodophenyl)-3-(p-phenylene)tridecanoic acid] wurde fuer Untersuchungen von koronaren Herzerkrankungen und Kardiomyopathien unterschiedlicher Genese entwickelt. Die Verbindung enthaelt eine in der Fettsaeurekette lokalisierte Phenylengruppe. Obwohl dieses Strukturelement raumfordernd ist, wird [{sup 123}I]PHIPA 3-10 aehnlich gut vom Herzmuskel aufgenommen, wie die unmodifizierte Fettsaeure [{sup 123}I]IPPA. Die auffallende

  7. The association between concentration of Uric Acid and metabolic syndrome among adolescents

    Directory of Open Access Journals (Sweden)

    Homeira Rashidi

    2015-11-01

    Full Text Available Background: Metabolic syndromes are known as a set of risk factors for the development of cardio-vascular disease and diabetes in the individual. The association between concentration of uric acid and metabolic syndrome in adolescents has yet to be established thoroughly. The aim of this study was to investigate the relationship between uric acid and metabolic syndrome in a sample of adolescents. Methods: This cross-sectional study was conducted from September 23, 2009 to September 22, 2010 in Jundishapur University of Medical Sciences, Ahvaz, Iran. In this study, 240 individuals aged 10-19 years were randomly selected among participants of the Ahvaz MetS study (120 subjects normal and 120 subjects MetS. The serum levels of UA were measured by a colorimetric method. In the normal group, anyone with abdominal obesity, high systolic or diastolic blood pressure, High-density lipoprotein (HDL≤40 mg/dl, TG≤110 mg/dl, fasting blood sugar (FBS≤100 mg/dl or diabetes was excluded from the study. History of Anticonvulsive drugs or steroids use was the criteria for exclusion for both groups. Results: Of the 240 subjects aged a mean of 14.95±2.64 years, mean of uric acid in metabolic syndrome group was 4.8±1.4 mg/dl and in the control group was 4.18±1.01 mg/d (P=0.001. Participants were divided into three groups based on uric acid levels: ≤4.9 mg/dl, 4.9-5.7 mg/dl and >5.7 mg/dl. The risk of metabolic syndrome was significantly higher in third group of uric acid than the second and first group (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.70 - 8.04 and (OR, 5.9; 95% CI, 2.42-14.35, P<0.001. In addition, uric acid level was inversely associated with hyperglycemia. The ORs of hypertriglyceridemia for the second and third group of uric acid were 4.36 (95% CI, 2.01- 9.47 5.75 (95% CI, 2.43-13.61 respectively, compared with lowest group of UA. Conclusion: The results showed that hyperuricemia was significantly linked with increased risk for

  8. Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat.

    Science.gov (United States)

    Roda, Aldo; Pellicciari, Roberto; Gioiello, Antimo; Neri, Flavia; Camborata, Cecilia; Passeri, Daniela; De Franco, Francesca; Spinozzi, Silvia; Colliva, Carolina; Adorini, Luciano; Montagnani, Marco; Aldini, Rita

    2014-07-01

    We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (a selective farnesoid X receptor [FXR] receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (a specific Takeda G protein-coupled receptor 5 [TGR5] receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, water solubility, lipophilicity, detergency, and protein binding. Biliary secretion and metabolism and plasma and hepatic concentrations were evaluated by high-pressure liquid chromatography-electrospray-mass spectrometry/mass spectrometry in bile fistula rat and compared with natural analogs chenodeoxycholic, cholic acid, and taurochenodexycholic acid and intestinal bacteria metabolism was evaluated in terms of 7α-dehydroxylase substrate-specificity in anaerobic human stool culture. The semisynthetic derivatives detergency, measured in terms of their critical micellar concentration, was quite similar to the natural analogs. They were slightly more lipophilic than the corresponding natural analogs, evaluated by their 1-octanol water partition coefficient (log P), because of the ethyl group in 6 position, which makes these molecules very stable toward bacterial 7-dehydroxylation. The hepatic metabolism and biliary secretion were different: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid, as chenodeoxycholic acid, was efficiently conjugated with taurine in the liver and, only in this form, promptly and efficiently secreted in bile. 6α-Ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid was poorly conjugated with taurine because of the steric hindrance of the methyl at C23(S) position metabolized to the C23(R) isomer and partly conjugated with taurine. Conversely, 6

  9. Metabolism

    Science.gov (United States)

    ... also influenced by body composition — people with more muscle and less fat generally have higher BMRs. previous continue Things That Can Go Wrong With Metabolism Most of the time your metabolism works effectively ...

  10. [Practical diagnostics of acid-base disorders: part I: differentiation between respiratory and metabolic disturbances].

    Science.gov (United States)

    Deetjen, P; Lichtwarck-Aschoff, M

    2012-11-01

    The first part of this overview on diagnostic tools for acid-base disorders focuses on basic knowledge for distinguishing between respiratory and metabolic causes of a particular disturbance. Rather than taking sides in the great transatlantic or traditional-modern debate on the best theoretical model for understanding acid-base physiology, this article tries to extract what is most relevant for everyday clinical practice from the three schools involved in these keen debates: the Copenhagen, the Boston and the Stewart schools. Each school is particularly strong in a specific diagnostic or therapeutic field. Appreciating these various strengths a unifying, simplified algorithm together with an acid-base calculator will be discussed.

  11. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  12. Influence of trans fatty acids on linoleic acid metabolism in the rat

    NARCIS (Netherlands)

    J.L. Zevenbergen

    1988-01-01

    textabstractAt the start of the work described in this thesis, most reviewers on trans fatty acids agreed that these isomeric fatty acids did not induce undesirable effects, provided sufficient linoleic acid was present in the diet (Beare-Rogers, 1983; Emken, 1983; Gottenbos, 1983; Gurr, 1983). Howe

  13. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

    DEFF Research Database (Denmark)

    Hoeft, B.; Linseisen, J.; Beckmann, L.;

    2010-01-01

    Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

  14. Lysophosphatidic acid metabolism and elimination in cardiovascular disease

    Science.gov (United States)

    Salous, Abdelghaffar Kamal

    The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are present in human and mouse plasma at a concentration of ~0.1-1 microM and regulate physiological and pathophysiological processes in the cardiovascular system including atherothrombosis, intimal hyperplasia, and immune function, edema formation, and permeability. PPAP2B, the gene encoding LPP3, a broad activity integral membrane enzyme that terminates LPA actions in the vasculature, has a single nucleotide polymorphism that been recently associated with coronary artery disease risk. The synthesis and signaling of LPA and S1P in the cardiovascular system have been extensively studied but the mechanisms responsible for their elimination are less well understood. The broad goal of this research was to examine the role of LPP3 in the termination of LPA signaling in models of cardiovascular disease involving vascular wall cells, investigate the role of LPP3 in the elimination of plasma LPA, and further characterize the elimination of plasma LPA. The central hypothesis is that LPP3 plays an important role in attenuating the pathological responses to LPA signaling and that it mediates the elimination of exogenously applied bioactive lipids from the plasma. These hypotheses were tested using molecular biological approaches, in vitro studies, synthetic lysophospholipid mimetics, modified surgical procedures, and mass spectrometry assays. My results indicated that LPP3 played a critical role in attenuating LPA signaling mediating the pathological processes of intimal hyperplasia and vascular leak in mouse models of disease. Additionally, enzymatic inactivation of lysophospholipids by LPP and PLA enzymes in the plasma was not a primary mechanism for the rapid elimination of plasma LPA and S1P. Instead, evidence strongly suggested a transcellular uptake mechanism by hepatic non-parenchymal cells as the predominant mechanism for elimination of these molecules. These results support a model in

  15. Phytic acid and raffinose series oligosaccharides metabolism in developing chickpea seeds.

    Science.gov (United States)

    Zhawar, Vikramjit Kaur; Kaur, Narinder; Gupta, Anil Kumar

    2011-10-01

    Phytic acid and raffinose series oligosaccharides (RFOs) have anti-nutritional properties where phytic acid chelates minerals and reduces their bioavailability to humans and other animals, and RFOs cause flatulence. Both phytic acid and RFOs cannot be digested by monogastric animals and are released as pollutant-wastes. Efforts are being made to reduce the contents of these factors without affecting the viability of seeds. This will require a thorough understanding of their metabolism in different crops. Biosynthetic pathways of both metabolites though are interlinked but not well described. This study was made on metabolism of these two contents in developing chickpea (Cicer arietinum L cv GL 769) seeds. In this study, deposition of RFOs was found to occur before deposition of phytic acid. A decline in inorganic phosphorus and increase in phospholipid phosphorus and phytic acid was observed in seeds during development. Acid phosphatase was the major phosphatase in seed as well as podwall and its activity was highest at early stage of development, thereafter it decreased. Partitioning of (14) C label from (14) C-glucose and (14) C-sucrose into RFOs and phytic acid was studied in seeds in presence of inositol, galactose and iositol and galactose, which favored the view that galactinol synthase is not the key enzyme in RFOs synthesis.

  16. L-(4-/sup 11/C)aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, J.R.; Egbert, J.E.; Henze, E.; Schelbert, H.R.; Baumgartner, F.J.

    1982-01-01

    Sterile, pyrogen-free L-(4-/sup 11/C)aspartic acid was prepared from /sup 11/CO/sub 2/ using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-(4-/sup 11/C)aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of /sup 11/CO/sub 2/ 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of /sup 11/CO/sub 2/. Positron-computed tomography imaging showed that the /sup 11/C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-(4-/sup 11/C)aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-(4-/sup 11/C)aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism.

  17. Effect of Non-Esterified Fatty Acids on Fatty Acid Metabolism-Related Genes in Calf Hepatocytes Cultured in Vitro

    Directory of Open Access Journals (Sweden)

    Peng Li

    2013-11-01

    Full Text Available Background: NEFA plays numerous roles in the metabolism of glucose, lipids, and proteins. A number of experimental studies have shown that NEFA may have an important role in fatty acid metabolism in the liver, especially in dairy cows that experience negative energy balance (NEB during early lactation. Methods: In this study, using fluorescent quantitative RT-PCR, ELISA, and primary hepatocytes cultured in vitro, we examined the effect of NEFA (0, 0.2, 0.4, 0.8, 1.6, and 3.2 mmol/L on fatty acid metabolism by monitoring the mRNA and protein expression of the following key enzymes: long chain acyl-CoA synthetase (ACSL, carnitine palmitoyltransferase IA (CPT IA, long chain acyl-CoA dehydrogenase (ACADL, and acetyl-CoA carboxylase (ACC. Results: The mRNA and protein expression levels of ACSL and ACADL markedly increased as the concentration of NEFA in the media was increased. The mRNA and protein expression levels of CPT IA were enhanced significantly when the NEFA concentrations increased from 0 to 1.6 mmol/L and decreased significantly when the NEFA concentrations increased from 1.6 to 3.2 mmol/L. The mRNA and protein expression of ACC decreased gradually with increasing concentrations of NEFA. Conclusion: These findings indicate that increased NEFA significantly promote the activation and β-oxidation of fatty acids, but very high NEFA concentrations may inhibit the translocation of fatty acids into mitochondria of hepatocytes. This may explain the development of ketosis or liver lipidosis in dairy cows. CPT IA might be the key control enzyme of the fatty acid oxidation process in hepatocytes.

  18. Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120

    DEFF Research Database (Denmark)

    Ulven, Trond; Christiansen, Elisabeth

    2015-01-01

    for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also......It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides...

  19. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    Science.gov (United States)

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  20. Metabolic regulation of the plant hormone indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  1. Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

    Directory of Open Access Journals (Sweden)

    Kyle J. Burghardt

    2013-01-01

    Full Text Available Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1 and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226 or bipolar disorder (n=94 were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

  2. Influence of photoperiod on growth for three desert CAM species. [Agave deserti, Ferocactus acanthodes, Opuntia ficus-indica

    Energy Technology Data Exchange (ETDEWEB)

    Nobel, P.S. (Univ. of California, Los Angeles (USA))

    1989-03-01

    Agave deserti, Ferocactus acanthodes, and Opuntia ficus-indica were maintained in environmental growth chambers under a constant total daily photosynthetically active radiation (PAR) for 1 yr to investigate the effects of photoperiod on growth of these Crassulacean acid metabolism (CAM) species. As the photoperiod was increased from 6 h to 18 h, growth increased 33% for A. deserti, 81% for F. acanthodes, and 50% for O. ficus-indica. Such increases were explained based on PAR saturation of the C{sub 3} photosynthetic carbon reduction cycle utilized by CAM plants during the daytime. In particular, the highest instantaneous PAR occurred for the shortest photoperiod and led to less growth for the same total daily PAR. Also, the total daily net CO{sub 2} uptake which occurred primarily at night, increased 53% as the photoperiod was increased from 6 to 18 h for O. ficus-indica, even though the accompanying night length decreased. The only other observed morphological effect was the sevenfold increase in the number of new cladodes initiated as the photoperiod was increased from 6 h to 18 h for O. ficus-indica. The influence of photoperiod on the daily pattern of net CO{sub 2} uptake and lack of effect of drought on plant survival under long photoperiods for O. ficus-indica differ from previous reports on this and other CAM species.

  3. Myogenic and metabolic feedback in cerebral autoregulation: Putative involvement of arachidonic acid-dependent pathways.

    Science.gov (United States)

    Berg, Ronan M G

    2016-07-01

    The present paper presents a mechanistic model of cerebral autoregulation, in which the dual effects of the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) on vascular smooth muscle mediate the cerebrovascular adjustments to a change in cerebral perfusion pressure (CPP). 20-HETE signalling in vascular smooth muscle mediates myogenic feedback to changes in vessel wall stretch, which may be modulated by metabolic feedback through EETs released from astrocytes and endothelial cells in response to changes in brain tissue oxygen tension. The metabolic feedback pathway is much faster than 20-HETE-dependent myogenic feedback, and the former thus initiates the cerebral autoregulatory response, while myogenic feedback comprises a relatively slower mechanism that functions to set the basal cerebrovascular tone. Therefore, assessments of dynamic cerebral autoregulation, which may provide information on the response time of the cerebrovasculature, may specifically be used to yield information on metabolic feedback mechanisms, while data based on assessments of static cerebral autoregulation represent the integrated functionality of myogenic and metabolic feedback. PMID:27241246

  4. Effect of dietary fatty acids on metabolic rate and nonshivering thermogenesis in golden hamsters.

    Science.gov (United States)

    Jefimow, Małgorzata; Wojciechowski, Michał S

    2014-02-01

    Hibernating rodents prior to winter tend to select food rich in polyunsaturated fatty acids (PUFA). Several studies found that such diet may positively affect their winter energy budget by enhancing torpor episodes. However, the effect of composition of dietary fatty acids (FA) on metabolism of normothermic heterotherms is poorly understood. Thus we tested whether diets different in FA composition affect metabolic rate (MR) and the capacity for nonshivering thermogenesis (NST) in normothermic golden hamsters (Mesocricetus auratus). Animals were housed in outdoor enclosures from May 2010 to April 2011 and fed a diet enriched with PUFA (i.e., standard food supplemented weekly with sunflower and flax seeds) or with saturated and monounsaturated fatty acids (SFA/MUFA, standard food supplemented with mealworms). Since diet rich in PUFA results in lower MR in hibernating animals, we predicted that PUFA-rich diet would have similar effect on MR of normothermic hamsters, that is, normothermic hamsters on the PUFA diet would have lower metabolic rate in cold and higher NST capacity than hamsters supplemented with SFA/MUFA. Indeed, in winter resting metabolic rate (RMR) below the lower critical temperature was higher and NST capacity was lower in SFA/MUFA-supplemented animals than in PUFA-supplemented ones. These results suggest that the increased capacity for NST in PUFA-supplemented hamsters enables them lower RMR below the lower critical temperature of the thermoneural zone.

  5. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective.

    Science.gov (United States)

    Schönfeld, Peter; Wojtczak, Lech

    2016-06-01

    Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and anabolic processes in mammals. SCFAs are mostly generated by colonic bacteria and are predominantly metabolized by enterocytes and liver, whereas MCFAs arise mostly from dietary triglycerides, among them milk and dairy products. A common feature of SCFAs and MCFAs is their carnitine-independent uptake and intramitochondrial activation to acyl-CoA thioesters. Contrary to long-chain fatty acids, the cellular metabolism of SCFAs and MCFAs depends to a lesser extent on fatty acid-binding proteins. SCFAs and MCFAs modulate tissue metabolism of carbohydrates and lipids, as manifested by a mostly inhibitory effect on glycolysis and stimulation of lipogenesis or gluconeogenesis. SCFAs and MCFAs exert no or only weak protonophoric and lytic activities in mitochondria and do not significantly impair the electron transport in the respiratory chain. SCFAs and MCFAs modulate mitochondrial energy production by two mechanisms: they provide reducing equivalents to the respiratory chain and partly decrease efficacy of oxidative ATP synthesis. PMID:27080715

  6. Nucleic Acids and Protein Metabolism of Bone Marrow Cells Studied by Means of Tritiumlabelled Precursors

    International Nuclear Information System (INIS)

    The advantages of the use of tritium-labelled compounds in radioautographic technique are discussed. Tritium electrons have a maximal energy of 0.018 MeV, corresponding to about 1μm range in a photographic emulsion, and consequently they allow the highest possible resolution at a cellular and subcellular level. This is particularly useful for studying metabolic phenomena of tissues which are composed, as in the case of bone marrow, of different cellular types at various stages of differentiation. This technique has been used for investigating nucleic acids and protein metabolism of normal and leukaemic bone marrow cells. DNA metabolism has been studied utilizing a specific precursor, H3-thymidine. Some significant differences of the percentages of labelled cells have been detected by comparing the normal and leukaemic elements belonging to the same stage of maturation. In acute leukaemia cells, particularly, a strikingly lower incorporation of thymidine was found and these results have been taken as evidence of a decreased proliferative capacity of these cells, as compared to normal myeloblasts. With the same technique, RNA and protein metabolism have been investigated utilizing H3- uridine, H3-leucine and H3-phenylalanine as precursors. The existence of a strict interrelationship between RNA and protein metabolism is now fully accepted in cellular biology. The existence of a constant ratio between uridine and amino acids incorporation has also been demonstrated in normal bone marrow cells. In acute leukaemia cells the incorporation of RNA and protein precursors, although different from case to case, is constantly and significantly lower. Furthermore, the ratio between uridine and amino acids incorporation is constantly altered in these cells. The lower RNA and protein metabolism and its dissociation in acute leukaemia cells is discussed in relation to the well-known maturation defect of these cells. (author)

  7. Eddy covariance measurements of net C exchange in the CAM bioenergy crop, Agave tequiliana

    Science.gov (United States)

    Owen, Nick A.; Choncubhair, Órlaith Ní; Males, Jamie; del Real Laborde, José Ignacio; Rubio-Cortés, Ramón; Griffiths, Howard; Lanigan, Gary

    2016-04-01

    Bioenergy crop cultivation may focus more on low grade and marginal lands in order to avoid competition with food production for land and water resources. However, in many regions, this would require improvements in plant water-use efficiency that are beyond the physiological capacity of most C3 and C4 bioenergy crop candidates. Crassulacean acid metabolism (CAM) plants, such as Agave tequiliana, can combine high above-ground productivity with as little as 20% of the water demand of C3 and C4 crops. This is achieved through temporal separation of carboxylase activities, with stomata opening at night to allow gas exchange and minimise transpirational losses. Previous studies have employed 'bottom-up' methodologies to investigate carbon (C) accumulation and productivity in Agave, by scaling leaf-level gas exchange and titratable acidity (TA) with leaf area index or maximum productivity. We used the eddy covariance (EC) technique to quantify ecosystem-scale gas exchange over an Agave plantation in Mexico ('top-down' approach). Measurements were made over 252 days, including the transition from wet to dry periods. Results were cross-validated against diel changes in titratable acidity, leaf-unfurling rates, energy exchange fluxes and reported biomass yields. Net ecosystem exchange of CO2 displayed a CAM rhythm that alternated from a net C sink at night to a net C source during the day and partitioned canopy fluxes (gross C assimilation, FA,EC) showed a characteristic four-phase CO2 exchange pattern. The projected ecosystem C balance indicated that the site was a net sink of -333 ± 24 g C m-2 y-1, comprising cumulative soil respiration of 692 ± 7 g C m-2 y-1 and FA,EC of -1025 ± 25 g C m-2 y-1. EC-estimated biomass yield was 20.1 Mg ha-1 y-1. Average integrated daily FA,EC was -234 ± 5 mmol CO2 m-2 d-1 and persisted almost unchanged after 70 days of drought conditions. Our results suggest that the carbon acquisition strategy of drought avoidance employed by Agave

  8. Eddy covariance measurements of net C exchange in the CAM bioenergy crop, Agave tequiliana

    Science.gov (United States)

    Owen, Nick A.; Choncubhair, Órlaith Ní; Males, Jamie; del Real Laborde, José Ignacio; Rubio-Cortés, Ramón; Griffiths, Howard; Lanigan, Gary

    2016-04-01

    Bioenergy crop cultivation may focus more on low grade and marginal lands in order to avoid competition with food production for land and water resources. However, in many regions, this would require improvements in plant water-use efficiency that are beyond the physiological capacity of most C3 and C4 bioenergy crop candidates. Crassulacean acid metabolism (CAM) plants, such as Agave tequiliana, can combine high above-ground productivity with as little as 20% of the water demand of C3 and C4 crops. This is achieved through temporal separation of carboxylase activities, with stomata opening at night to allow gas exchange and minimise transpirational losses. Previous studies have employed 'bottom-up' methodologies to investigate carbon (C) accumulation and productivity in Agave, by scaling leaf-level gas exchange and titratable acidity (TA) with leaf area index or maximum productivity. We used the eddy covariance (EC) technique to quantify ecosystem-scale gas exchange over an Agave plantation in Mexico ('top-down' approach). Measurements were made over 252 days, including the transition from wet to dry periods. Results were cross-validated against diel changes in titratable acidity, leaf-unfurling rates, energy exchange fluxes and reported biomass yields. Net ecosystem exchange of CO2 displayed a CAM rhythm that alternated from a net C sink at night to a net C source during the day and partitioned canopy fluxes (gross C assimilation, FA,EC) showed a characteristic four-phase CO2 exchange pattern. The projected ecosystem C balance indicated that the site was a net sink of -333 ± 24 g C m‑2 y‑1, comprising cumulative soil respiration of 692 ± 7 g C m‑2 y‑1 and FA,EC of -1025 ± 25 g C m‑2 y‑1. EC-estimated biomass yield was 20.1 Mg ha‑1 y‑1. Average integrated daily FA,EC was -234 ± 5 mmol CO2 m‑2 d‑1 and persisted almost unchanged after 70 days of drought conditions. Our results suggest that the carbon acquisition strategy of drought avoidance

  9. Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica.

    Science.gov (United States)

    Xue, Zhixiong; Sharpe, Pamela L; Hong, Seung-Pyo; Yadav, Narendra S; Xie, Dongming; Short, David R; Damude, Howard G; Rupert, Ross A; Seip, John E; Wang, Jamie; Pollak, Dana W; Bostick, Michael W; Bosak, Melissa D; Macool, Daniel J; Hollerbach, Dieter H; Zhang, Hongxiang; Arcilla, Dennis M; Bledsoe, Sidney A; Croker, Kevin; McCord, Elizabeth F; Tyreus, Bjorn D; Jackson, Ethel N; Zhu, Quinn

    2013-08-01

    The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is currently limited because they are produced mainly by marine fisheries that cannot keep pace with the demands of the growing market for these products. A sustainable non-animal source of EPA and DHA is needed. Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a strain that produced EPA at 15% of dry cell weight. The engineered yeast lipid comprises EPA at 56.6% and saturated fatty acids at less than 5% by weight, which are the highest and the lowest percentages, respectively, among known EPA sources. Inactivation of the peroxisome biogenesis gene PEX10 was crucial in obtaining high EPA yields and may increase the yields of other commercially desirable lipid-related products. This technology platform enables the production of lipids with tailored fatty acid compositions and provides a sustainable source of EPA.

  10. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    Science.gov (United States)

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower ( 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  11. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Directory of Open Access Journals (Sweden)

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

  12. Metabolic engineering of lactic acid bacteria for the production of industrially important compounds

    Directory of Open Access Journals (Sweden)

    Maria Papagianni

    2012-10-01

    Full Text Available Lactic acid bacteria (LAB are receiving increased attention for use as cell factories for the production of metabolites with wide use by the food and pharmaceutical industries. The availability of efficient tools for genetic modification of LAB during the past decade permitted the application of metabolic engineering strategies at the levels of both the primary and the more complex secondary metabolism. The recent developments in the area with a focus on the production of industrially important metabolites will be discussed in this review.

  13. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia

    OpenAIRE

    Kaliannan, Kanakaraju; Wang, Bin; Li, Xiang-Yong; Kim, Kui-Jin; Kang, Jing X.

    2015-01-01

    Metabolic endotoxemia, commonly derived from gut dysbiosis, is a primary cause of chronic low grade inflammation that underlies many chronic diseases. Here we show that mice fed a diet high in omega-6 fatty acids exhibit higher levels of metabolic endotoxemia and systemic low-grade inflammation, while transgenic conversion of tissue omega-6 to omega-3 fatty acids dramatically reduces endotoxemic and inflammatory status. These opposing effects of tissue omega-6 and omega-3 fatty acids can be e...

  14. Metabolic engineering of lactic acid bacteria and characterization of novel enzymes for the production of industrially important compounds

    OpenAIRE

    Aarnikunnas, Johannes Sakari

    2006-01-01

    Lactic acid bacteria (LAB) are a heterogeneous group of gram-positive bacteria that produce lactic acid as their main end-product during sugar fermentation. Because the LAB are able to rapidly lower pH through acid formation and additionally produce many flavor compounds, they are commonly used in the food and feed industry. LAB are also attractive organisms for metabolic engineering because their energy metabolism is generally not connected to their biosynthetic activity. Therefore, their su...

  15. Cadmium Induces Retinoic Acid Signaling by Regulating Retinoic Acid Metabolic Gene Expression*

    OpenAIRE

    Cui, Yuxia; Freedman, Jonathan H.

    2009-01-01

    The transition metal cadmium is an environmental teratogen. In addition, cadmium and retinoic acid can act synergistically to induce forelimb malformations. The molecular mechanism underlying the teratogenicity of cadmium and the synergistic effect with retinoic acid has not been addressed. An evolutionarily conserved gene, β,β-carotene 15,15′-monooxygenase (BCMO), which is involved in retinoic acid biosynthesis, was studied in both Caenorhabditis elegans and murine Hepa 1–6 cells. In C. eleg...

  16. Trehalose 6-phosphate coordinates organic and amino acid metabolism with carbon availability.

    Science.gov (United States)

    Figueroa, Carlos M; Feil, Regina; Ishihara, Hirofumi; Watanabe, Mutsumi; Kölling, Katharina; Krause, Ursula; Höhne, Melanie; Encke, Beatrice; Plaxton, William C; Zeeman, Samuel C; Li, Zhi; Schulze, Waltraud X; Hoefgen, Rainer; Stitt, Mark; Lunn, John E

    2016-02-01

    Trehalose 6-phosphate (Tre6P) is an essential signal metabolite in plants, linking growth and development to carbon metabolism. The sucrose-Tre6P nexus model postulates that Tre6P acts as both a signal and negative feedback regulator of sucrose levels. To test this model, short-term metabolic responses to induced increases in Tre6P levels were investigated in Arabidopsis thaliana plants expressing the Escherichia coli Tre6P synthase gene (otsA) under the control of an ethanol-inducible promoter. Increased Tre6P levels led to a transient decrease in sucrose content, post-translational activation of nitrate reductase and phosphoenolpyruvate carboxylase, and increased levels of organic and amino acids. Radio-isotope ((14)CO2) and stable isotope ((13)CO2) labelling experiments showed no change in the rates of photoassimilate export in plants with elevated Tre6P, but increased labelling of organic acids. We conclude that high Tre6P levels decrease sucrose levels by stimulating nitrate assimilation and anaplerotic synthesis of organic acids, thereby diverting photoassimilates away from sucrose to generate carbon skeletons and fixed nitrogen for amino acid synthesis. These results are consistent with the sucrose-Tre6P nexus model, and implicate Tre6P in coordinating carbon and nitrogen metabolism in plants. PMID:26714615

  17. [Succinic acid production from sucrose and sugarcane molasses by metabolically engineered Escherichia coli].

    Science.gov (United States)

    Li, Feng; Ma, Jiangfeng; Wu, Mingke; Ji, Yaliang; Chen, Wufang; Ren, Xinyi; Jiang, Min

    2015-04-01

    Sugarcane molasses containing large amounts of sucrose is an economical substrate for succinic acid production. However, Escherichia coli AFP111 cannot metabolize sucrose although it is a promising candidate for succinic acid production. To achieve sucrose utilizing ability, we cloned and expressed cscBKA genes encoding sucrose permease, fructokinase and invertase of non-PTS sucrose-utilization system from E. coli W in E. coli AFP111 to generate a recombinant strain AFP111/pMD19T-cscBKA. After 72 h of anaerobic fermentation of the recombinant in serum bottles, 20 g/L sucrose was consumed and 12 g/L succinic acid was produced. During dual-phase fermentation comprised of initial aerobic growth phase followed by anaerobic fermentation phase, the concentration of succinic acid from sucrose and sugarcane molasses was 34 g/L and 30 g/L, respectively, at 30 h of anaerobic phase in a 3 L fermentor. The results show that the introduction of non-PTS sucrose-utilization system has sucrose-metabolizing capability for cell growth and succinic acid production, and can use cheap sugarcane molasses to produce succinic acid.

  18. The effect of the creatine analogue beta-guanidinopropionic acid on energy metabolism: a systematic review.

    Directory of Open Access Journals (Sweden)

    Inge Oudman

    Full Text Available BACKGROUND: Creatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands. METHODS: We performed a systematic review and searched the electronic databases Pubmed, EMBASE, the Cochrane Library, and LILACS from their inception through March 2011. Furthermore, we searched the internet and explored references from textbooks and reviews. RESULTS: After applying the inclusion criteria, we retrieved 131 publications, mainly considering the effect of chronic oral administration of beta-guanidinopropionic acid (0.5 to 3.5% on skeletal muscle, the cardiovascular system, and brain tissue in animals. Beta-guanidinopropionic acid decreased intracellular creatine and phosphocreatine in all tissues studied. In skeletal muscle, this effect induced a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake and increased fatigue tolerance. In heart tissue this shift to mitochondrial metabolism was less pronounced. Myocardial contractility was modestly reduced, including a decreased ventricular developed pressure, albeit with unchanged cardiac output. In brain tissue adaptations in energy metabolism resulted in enhanced ATP stability and survival during hypoxia. CONCLUSION: Chronic beta-guanidinopropionic acid increases fatigue tolerance of skeletal muscle and survival during ischaemia in animal studies, with modestly reduced myocardial contractility. Because it is marked as safe for human

  19. Effects of ascorbic acid and sodium ascorbate on cyclic nucleotide metabolism in human lymphocytes.

    Science.gov (United States)

    Atkinson, J P; Weiss, A; Ito, M; Kelly, J; Parker, C W

    1979-01-01

    L-ascorbic acid (LAA) augmented cGMP many-fold in highly purified human peripheral blood lymphocytes. The cGMP response occurred within 10 sec and persisted for at least 60 min. D-ascorbic acid (DAA) and dehydroascorbic acid (DHAA) were also equally active in enhancing cGMP concentrations but metabolic precursors of ascorbic acid and other inorganic acids did not increase cGMP levels. Determination of the amount of DHAA contaminating the LAA precluded the possibility that it was solely responsible for the enhanced cGMP levels. The sodium or calcium salts of ascorbic acid did not increase cGMP concentrations. If these neutralized preparations were acidified, increased cGMP concentrations were then noted. In broken cell preparations, LAA, DAA, and DHAA and to a lesser extent sodium ascorbate (NaA) enhanced guanylate cyclase activity while neither inhibited cAMP or cGMP phosphodiesterase (PDE) activity. The possible role of H2O2, fatty acid liberation, prostaglandin production, oxidizing-reducing agents, and free radical formation in mediating the effects of ascorbic acid on cGMP levels were evaluated, but none of these potential mechanisms were definitively proven to be a required intermediary for the cGMP enhancing activity of ascorbic acid. LAA, DHAA or NaA did not induce lymphocyte transformation or modulate lectin-induced mitogenesis. PMID:36416

  20. A central role of abscisic acid in stress-regulated carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Stefan Kempa

    Full Text Available BACKGROUND: Abiotic stresses adversely affect plant growth and development. The hormone abscisic acid (ABA plays a central role in the response and adaptation to environmental constraints. However, apart from the well established role of ABA in regulating gene expression programmes, little is known about its function in plant stress metabolism. PRINCIPAL FINDINGS: Using an integrative multiparallel approach of metabolome and transcriptome analyses, we studied the dynamic response of the model glyophyte Arabidopsis thaliana to ABA and high salt conditions. Our work shows that salt stress induces complex re-adjustment of carbohydrate metabolism and that ABA triggers the initial steps of carbon mobilisation. SIGNIFICANCE: These findings open new perspectives on how high salinity and ABA impact on central carbohydrate metabolism and highlight the power of iterative combinatorial approaches of non-targeted and hypothesis-driven experiments in stress biology.

  1. Genetic Investigation of Tricarboxylic Acid Metabolism during the Plasmodium falciparum Life Cycle

    Directory of Open Access Journals (Sweden)

    Hangjun Ke

    2015-04-01

    Full Text Available New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO lines that delete six of the eight mitochondrial tricarboxylic acid (TCA cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of 13C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development.

  2. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers.

    Science.gov (United States)

    Mayers, Jared R; Torrence, Margaret E; Danai, Laura V; Papagiannakopoulos, Thales; Davidson, Shawn M; Bauer, Matthew R; Lau, Allison N; Ji, Brian W; Dixit, Purushottam D; Hosios, Aaron M; Muir, Alexander; Chin, Christopher R; Freinkman, Elizaveta; Jacks, Tyler; Wolpin, Brian M; Vitkup, Dennis; Vander Heiden, Matthew G

    2016-09-01

    Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements. PMID:27609895

  3. IBD and Complementary and Alternative Medicine (CAM)

    Science.gov (United States)

    ... Alternative Medicine (CAM) Go Back Complementary and Alternative Medicine (CAM) Email Print + Share Crohn’s disease and ulcerative ... Energy Medicine, and Biologically-Based Practices. Mind-Body Medicine Mind-body medicine is a set of interventions ...

  4. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  5. The metabolism of L-[6-14C] ascorbic acid in detached grape leaves

    International Nuclear Information System (INIS)

    Grape leaves (Vitis labrusca L.) that are removed from the position opposite the flower cluster either 28 or 14 days before anthesis cleave L-ascorbic acid (AA) at the C4-C5 bond into a C4 and, presumably, a C2 fragment. Leaves taken from this position 14 days after anthesis fail to cleave AA. The C4 fragment is utilized for L(+)-tartaric acid (TA) biosynthesis while the C2 fragment is recycled into hexose and products of the hexose metabolism. When ( 6-14C ) AA is the source of the label, the sucrose-drived glucose from labeled leaves has a distribution of 14C in the carbon skeleton as follows: C1, 35%; C2, 14%; C3, 4%; C(4 + 5), 13% and C6, 34%. The effect of inhibitors of the glycolate pathway on ( 6-14C ) AA metabolism is examined. (author)

  6. The detection of EpCAM(+) and EpCAM(-) circulating tumor cells

    NARCIS (Netherlands)

    de Wit, Sanne; van Dalum, Guus; Lenferink, Aufried T. M.; Tibbe, Arjan G. J.; Hiltermann, T. Jeroen N.; Groen, Harry J. M.; van Rijn, Cees J. M.; Terstappen, Leon W. M. M.

    2015-01-01

    EpCAM expressing circulating tumor cells, detected by CellSearch, are predictive of short survival in several cancers and may serve as a liquid biopsy to guide therapy. Here we investigate the presence of EpCAM(+) CTC detected by CellSearch and EpCAM(-) CTC discarded by CellSearch, after EpCAM based

  7. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-08-01

    Full Text Available Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

  8. The Z CamPaign: Year Five

    CERN Document Server

    Simonsen, Mike

    2014-01-01

    Entering into the fifth year of the Z CamPaign, the author has developed a website summarizing our findings which will also act as a living catalog of bona fide Z Cam stars, suspected Z Cams and Z Cam impostors. In this paper we summarize the findings of the first four years of research, introduce the website and its contents to the public and discuss the way forward into year five and beyond.

  9. Research on Arachidonic Acid and Eicosapentaenoic Acid Anabolic Metabolism in Diasporangium sp.

    Institute of Scientific and Technical Information of China (English)

    DAI Chuan-chao; XU Yu-fen; XIA Shun-xiang; ZHAO Mo; YE Yu-cheng

    2010-01-01

    The fatty acids of a strain of Diasporangium sp.had been analyzed by using GC-MS.The fatty acids of twenty mutants were determined.Based on these results,the producing of eicosapentaenoic acid(EPA)supposed via 18∶2,18∶3,20∶3,20∶4 which all belong to ω-6 fatty acids.The ω-3 desaturation was undertaken at arachidonic acid(AA).In addition,mutant strains resulted in enhanced content of AA which could get two times more than initial strain,but no compact on EPA.

  10. Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cells

    International Nuclear Information System (INIS)

    The metabolism (chain elongation, desaturation, and incorporation into complex lipids) of thirteen different radiolabeled fatty acids and acetate was examined in N1E-115 neuroblastoma and C-6 glioma cell lines in culture. During 6-hr incubations, all fatty acids were extensively (14-80%) esterified to complex lipids, mainly choline phosphoglycerides and triacylglycerol. With trienoic and tetraenoic substrates, inositol and ethanolamine phosphoglycerides also contained up to 30% of the labeled fatty acids; plasmalogen contained up to half of the label in the ethanolamine phosphoglyceride fraction of neuroblastoma cells. Chain elongation and delta 9, delta 6, and delta 5 desaturation occurred in both cell lines; delta 4 desaturation was not observed. Seemingly anomalous utilization of arachidic acid and some selectivity based on the geometric configuration of double bonds was observed. These studies indicate that these cell lines are capable of modulating cellular membrane composition by a combination of selective exclusion and removal of inappropriate acyl chains and of modification of other acyl chains by desaturation and chain elongation. The time courses and patterns of modification and incorporation of exogenous substrates into phospholipids and triacylglycerol suggest that exogenous unsaturated fatty acid may be incorporated into triacylglycerol and later released for further metabolism and incorporation into phospholipids. This supports a role for triacylglycerol in the synthesis of membrane complex lipids in cell lines derived from neural tissue

  11. Proteomics-Based Metabolic Modeling Reveals That Fatty Acid Oxidation (FAO) Controls Endothelial Cell (EC) Permeability*

    Science.gov (United States)

    Patella, Francesca; Schug, Zachary T.; Persi, Erez; Neilson, Lisa J.; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R.; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-01-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability. PMID:25573745

  12. The chromatin remodeler DDM1 promotes hybrid vigor by regulating salicylic acid metabolism

    OpenAIRE

    Zhang, Qingzhu; Li, Yanqiang; Xu, Tao; Srivastava, Ashish Kumar; Dong WANG; Zeng, Liang; Yang, Lan; He, Li; Zhang, Heng; Zheng, Zhimin; Yang, Dong-Lei; Zhao, Cheng; Dong, Juan; Gong, Zhizhong; Liu, Renyi

    2016-01-01

    In plants, hybrid vigor is influenced by genetic and epigenetic mechanisms; however, the molecular pathways are poorly understood. We investigated the potential contributions of epigenetic regulators to heterosis in Arabidposis and found that the chromatin remodeler DECREASED DNA METHYLATION 1 (DDM1) affects early seedling growth heterosis in Col/C24 hybrids. ddm1 mutants showed impaired heterosis and increased expression of non-additively expressed genes related to salicylic acid metabolism....

  13. HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ting-I Lee

    2016-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs regulate cardiac glucose and lipid homeostasis. Histone deacetylase (HDAC inhibitor has anti-inflammatory effects which may play a key role in modulating PPARs and fatty acid metabolism. The aim of this study was to investigate whether HDAC inhibitor, MPT0E014, can modulate myocardial PPARs, inflammation, and fatty acid metabolism in diabetes mellitus (DM cardiomyopathy. Electrocardiography, echocardiography, and western blotting were used to evaluate the electrophysiological activity, cardiac structure, fatty acid metabolism, inflammation, and PPAR isoform expressions in the control and streptozotocin-nicotinamide-induced DM rats with or without MPT0E014. Compared to control, DM and MPT0E014-treated DM rats had elevated blood glucose levels and lower body weights. However, MPT0E014-treated DM and control rats had smaller left ventricular end-diastolic diameter and shorter QT interval than DM rats. The control and MPT0E014-treated DM rats had greater cardiac PPAR-α and PPAR-δ protein expressions, but less cardiac PPAR-γ than DM rats. Moreover, control and MPT0E014-treated DM rats had lower concentrations of 5′ adenosine monophosphate-activated protein kinase 2α, PPAR-γ coactivator 1α, phosphorylated acetyl CoA carboxylase, cluster of differentiation 36, diacylglycerol acyltransferase 1 (DGAT1, DGAT2, tumor necrosis factor-α, and interleukin-6 protein than DM rats. HDAC inhibition significantly attenuated DM cardiomyopathy through modulation of cardiac PPARS, fatty acid metabolism, and proinflammatory cytokines.

  14. Effects of Salinity: Calcium Interaction on Growth and Nucleic Acid Metabolism in Five Species of Chenopodiaceae

    OpenAIRE

    ABO-KASSEM, Essam El-Deen Mohaned

    2007-01-01

    Seed germination, seedling growth, and some enzyme activity of nucleic acid metabolism were studied in 5 members of Chenopodiaceae [Beta vulgaris L., Chenopodium quinoa Willd., Spinacea oleracea L., Allenrolfia occidentalis (S.Watson) Kuntze, Atriplex hortensis L.] under NaCl salinity alone or combined with 0.5 mM CaSO4. High salinity delayed radical emergence and decreased germination percentage in all plants. Combined CaSO4 reduced inhibition of seed germination in B. vulgaris, S. oleracea,...

  15. Characterization of the first enzyme in 2,4-dichlorophenoxyacetic acid metabolism.

    OpenAIRE

    Hausinger, R P; Fukumori, F

    1995-01-01

    This paper reviews the properties of the Alcaligenes eutrophus JMP134 tfdA gene product, the enzyme responsible for the first step in 2,4-dichlorophenoxyacetic acid (2,4-D) biodegradation. The gene was overexpressed in Escherichia coli and several of its enzymatic properties were characterized. Although this enzyme catalyzes a hydroxylation reaction, it is not a monooxygenase. Rather, TfdA is an Fe(II) and alpha-ketoglutarate-dependent dioxygenase that metabolizes the latter cosubstrate to su...

  16. Seasonal photosynthetic gas exchange and water-use efficiency in a constitutive CAM plant, the giant saguaro cactus (Carnegiea gigantea).

    Science.gov (United States)

    Bronson, Dustin R; English, Nathan B; Dettman, David L; Williams, David G

    2011-11-01

    Crassulacean acid metabolism (CAM) and the capacity to store large quantities of water are thought to confer high water use efficiency (WUE) and survival of succulent plants in warm desert environments. Yet the highly variable precipitation, temperature and humidity conditions in these environments likely have unique impacts on underlying processes regulating photosynthetic gas exchange and WUE, limiting our ability to predict growth and survival responses of desert CAM plants to climate change. We monitored net CO(2) assimilation (A(net)), stomatal conductance (g(s)), and transpiration (E) rates periodically over 2 years in a natural population of the giant columnar cactus Carnegiea gigantea (saguaro) near Tucson, Arizona USA to investigate environmental and physiological controls over carbon gain and water loss in this ecologically important plant. We hypothesized that seasonal changes in daily integrated water use efficiency (WUE(day)) in this constitutive CAM species would be driven largely by stomatal regulation of nighttime transpiration and CO(2) uptake responding to shifts in nighttime air temperature and humidity. The lowest WUE(day) occurred during time periods with extreme high and low air vapor pressure deficit (D(a)). The diurnal with the highest D(a) had low WUE(day) due to minimal net carbon gain across the 24 h period. Low WUE(day) was also observed under conditions of low D(a); however, it was due to significant transpiration losses. Gas exchange measurements on potted saguaro plants exposed to experimental changes in D(a) confirmed the relationship between D(a) and g(s). Our results suggest that climatic changes involving shifts in air temperature and humidity will have large impacts on the water and carbon economy of the giant saguaro and potentially other succulent CAM plants of warm desert environments. PMID:21822726

  17. Intestinal absorption and postabsorptive metabolism of linoleic acid in rats with short-term bile duct ligation

    NARCIS (Netherlands)

    Minich, DM; Havinga, R; Stellaard, F; Vonk, RJ; Kuipers, F; Verkade, HJ

    2000-01-01

    We investigated in bile duct-ligated (BDL) and sham-operated control rats whether the frequent presence of essential fatty acid deficiency in cholestatic liver disease could be related to linoleic acid malabsorption, altered linoleic acid metabolism, or both. In plasma of BDL rats, the triene-to-tet

  18. Combining rational metabolic engineering and flux optimization strategies for efficient production of fumaric acid.

    Science.gov (United States)

    Song, Chan Woo; Lee, Sang Yup

    2015-10-01

    Fumaric acid is an important C4-dicarboxylic acid widely used in chemical, food, and pharmaceutical industries. Rational metabolic engineering together with flux optimization were performed for the development of an Escherichia coli strain capable of efficiently producing fumaric acid. The initial engineered strain, CWF4N overexpressing phosphoenolpyruvate carboxylase (PPC), produced 5.30 g/L of fumaric acid. Optimization of PPC flux by examining 24 types of synthetic PPC expression vectors further increased the titer up to 5.72 g/L with a yield of 0.432 g/g·glucose. Overexpression of the succinate dehydrogenase complex (sdhCDAB) led to an increase in carbon yield up to 0.493 g/g·glucose. Based on this mutant strain, citrate synthase (CS) was combinatorially overexpressed and balanced with PPC using 48 types of synthetic expression vectors. As a result, 6.24 g/L of fumaric acid was produced with a yield of 0.500 g/g·glucose. Fed-batch culture of this final strain allowed production of 25.5 g/L of fumaric acid with a yield of 0.366 g/g·glucose. Deletion of the aspA gene encoding aspartase and supplementation of aspartic acid further increased the fumaric acid titer to 35.1 g/L with a yield of 0.490 g/g·glucose.

  19. Analysis of Growth Inhibition and Metabolism of Hydroxycinnamic Acids by Brewing and Spoilage Strains of Brettanomyces Yeast

    Directory of Open Access Journals (Sweden)

    Michael Lentz

    2015-10-01

    Full Text Available Brettanomyces yeasts are well-known as spoilage organisms in both the wine and beer industries, but also contribute important desirable characters to certain beer styles. These properties are mediated in large part by Brettanomyces’ metabolism of hydroxycinnamic acids (HCAs present in beverage raw materials. Here we compare growth inhibition by, and metabolism of, HCAs among commercial brewing strains and spoilage strains of B. bruxellensis and B. anomalus. These properties vary widely among the different strains tested and between the HCAs analyzed. Brewing strains showed more efficient metabolism of ferulic acid over p-coumaric acid, a trait not shared among the spoilage strains.

  20. Nocturnal uptake and assimilation of nitrogen dioxide by C3 and CAM plants.

    Science.gov (United States)

    Takahashi, Misa; Konaka, Daisuke; Sakamoto, Atsushi; Morikawa, Hiromichi

    2005-01-01

    In order to investigate nocturnal uptake and assimilation of NO2 by C3 and crassulacean acid metabolism (CAM) plants, they were fumigated with 4 microl l(-1) 15N-labeled nitrogen dioxide (NO2) for 8 h. The amount of NO2 and assimilation of NO2 by plants were determined by mass spectrometry and Kjeldahl-nitrogen based mass spectrometry, respectively. C3 plants such as kenaf (Hibiscus cannabinus), tobacco (Nicotiana tabacum) and ground cherry (Physalis alkekengi) showed a high uptake and assimilation during daytime as high as 1100 to 2700 ng N mg(-1) dry weight. While tobacco and ground cherry strongly reduced uptake and assimilation of NO2 during nighttime, kenaf kept high nocturnal uptake and assimilation of NO2 as high as about 1500 ng N mg(-1) dry weight. Stomatal conductance measurements indicated that there were no significant differences to account for the differences in the uptake of NO2 by tobacco and kenaf during nighttime. CAM plants such as Sedum sp., Kalanchoe blossfeldiana (kalanchoe) and Aloe arborescens exhibited nocturnal uptake and assimilation of NO2. However, the values of uptake and assimilation of NO2 both during daytime and nighttime was very low (at most about 500 ng N mg(-1) dry weight) as compared with those of above mentioned C3 plants. The present findings indicate that kenaf is an efficient phytoremediator of NO2 both during daytime and nighttime. PMID:15948596

  1. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID

  2. Uric Acid Metabolism in a Sample of Egyptian Hypertensive Patients With Normal Kidney Function

    Directory of Open Access Journals (Sweden)

    Adel Afifi, ¹ Iman Sarhan¹, Magdy El Sharkawy¹, Mostafa Kamel¹, Waleed Anwar ¹,

    2013-07-01

    Full Text Available Background: Hyperuricemia is commonly associated with hypertension. Also, it is well known to coincide with the metabolic syndrome but is still not recognized as a risk factor. So, we aimed to evaluate hyperuricemia among a sample of hypertensive Egyptians with normal renal function.Methods: this study was performed on 303 hypertensive patients aged 30-69 years. Patients were divided into 2 groups according to the level of uric acid: group 1 composed of 168 hypertensive hyperuricemic patient sand group2 composed of 135 hypertensive normouricemic patients. All patients were subjected to complete medical history and detailed clinical examination including body mass index (BMI, complete blood count (CBC, serum creatinine, BUN, FBS, cholesterol, triglycerides, uric acid, sodium, potassium, urinary uric acid, urinary creatinine, urinary uric acid to creatinine ratio and fractional excretion of uric acid(FEUA.Results: The overall prevalence of hyperuricemia was 55.4%. Uric acid correlated significantly with age (p0.05. Serum uric acid found to correlate significantly (p<0.001 with urinary uric acid, urinary creatinine and negatively with FEUA denoting early tubular defect of the kidney. Also, Urinary uric acid, urinary creatinine and urinary uric acid/creatinine ratio were higher in group 1than in group 2 (p values were<0.001, <0.001 and <0.05 respectively. FEUA was found to be significantly lower in group 1 than in group 2 (p<0.01. We found, also, that serum sodium level was significantly higher in the hyperuricemic group than in the normouricemic group (p<0.001 denoting the role of Na+ in the development of hypertension and defective renal excretion of uric acid.Conclusion: We conclude that the incidence hyperuricemia in our sample of Egyptian hypertensive patients was (55.4%. Impaired renal clearance of uric acid occurs before deterioration of GFR. Serum uric acid should be measured in all cases of hypertension together with BMI, total cholesterol

  3. Essential amino acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    Traditional methods used to evaluate protein metabolism left unanswered some of the relevant questions in public health in developing countries, such as growth retardation in children. Particularly, in developing countries, infection (clinical and subclinical) and malnutrition are still relevant problems, and the most important scientific issues for the application of stable isotope tracer methods are related to the impact of infection, such as the oxidative disposal of essential amino acids in well-nourished and malnourished children. The objectives of the present proposal are: (1) To simplify, make less expensive, less time-consuming, and less invasive, methods in clinical research on amino acid metabolism using stable-isotope tracers in children; and (2) To assess the effects of infection (clinical or subclinical) on whole-body protein turnover in children with and without malnutrition. The objectives involve the engineering and assessment of a portable instrument to be used in evaluations of protein oxidation in the developing world. Methodological issues such as intra- and inter-subject variability, which are of great importance for the interpretation of amino acid metabolism and protein turnover, will also be considered. 18 refs, 2 figs

  4. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    Directory of Open Access Journals (Sweden)

    Marijana Todorčević

    2015-12-01

    Full Text Available Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3 and docosahexaenoic acid (DHA; 22:6n-3. Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.

  5. The detection of EpCAM

    NARCIS (Netherlands)

    Wit, De Sanne; Dalum, Van Guus; Lenferink, Aufried T.M.; Tibbe, Arjan G.J.; Hiltermann, T.J.N.; Groen, Harry J.M.; Rijn, Van C.J.M.; Terstappen, Leon W.M.M.

    2015-01-01

    EpCAM expressing circulating tumor cells, detected by CellSearch, are predictive of short survival in several cancers and may serve as a liquid biopsy to guide therapy. Here we investigate the presence of EpCAM+ CTC detected by CellSearch and EpCAM- CTC discarded by CellSear

  6. Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets

    Directory of Open Access Journals (Sweden)

    John J. Shin

    2016-09-01

    Full Text Available A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV, mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln amidotransferase complex], histone methylation (Set1C–COMPASS, lysosome biogenesis (AP-3 adapter complex, and mRNA processing and P-body formation (PAN complex. We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial

  7. Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets.

    Science.gov (United States)

    Shin, John J; Aftab, Qurratulain; Austin, Pamela; McQueen, Jennifer A; Poon, Tak; Li, Shu Chen; Young, Barry P; Roskelley, Calvin D; Loewen, Christopher J R

    2016-09-01

    A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV), mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln) amidotransferase complex], histone methylation (Set1C-COMPASS), lysosome biogenesis (AP-3 adapter complex), and mRNA processing and P-body formation (PAN complex). We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial respiratory chain

  8. Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism.

    Science.gov (United States)

    Steffner, Robert J; Wu, Lan; Powers, Alvin C; May, James M

    2004-11-15

    Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells. PMID:15477012

  9. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  10. Modulation of tissue fatty acids by L-carnitine attenuates metabolic syndrome in diet-induced obese rats.

    Science.gov (United States)

    Panchal, Sunil K; Poudyal, Hemant; Ward, Leigh C; Waanders, Jennifer; Brown, Lindsay

    2015-08-01

    Obesity and dyslipidaemia are metabolic defects resulting from impaired lipid metabolism. These impairments are associated with the development of cardiovascular disease and non-alcoholic fatty liver disease. Correcting the defects in lipid metabolism may attenuate obesity and dyslipidaemia, and reduce cardiovascular risk and liver damage. L-Carnitine supplementation was used in this study to enhance fatty acid oxidation so as to ameliorate diet-induced disturbances in lipid metabolism. Male Wistar rats (8-9 weeks old) were fed with either corn starch or high-carbohydrate, high-fat diets for 16 weeks. Separate groups were supplemented with L-carnitine (1.2% in food) on either diet for the last 8 weeks of the protocol. High-carbohydrate, high-fat diet-fed rats showed central obesity, dyslipidaemia, hypertension, impaired glucose tolerance, hyperinsulinaemia, cardiovascular remodelling and non-alcoholic fatty liver disease. L-Carnitine supplementation attenuated these high-carbohydrate, high-fat diet-induced changes, together with modifications in lipid metabolism including the inhibition of stearoyl-CoA desaturase-1 activity, reduced storage of short-chain monounsaturated fatty acids in the tissues with decreased linoleic acid content and trans fatty acids stored in retroperitoneal fat. Thus, L-carnitine supplementation attenuated the signs of metabolic syndrome through inhibition of stearoyl-CoA desaturase-1 activity, preferential β-oxidation of some fatty acids and increased storage of saturated fatty acids and relatively inert oleic acid in the tissues.

  11. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  12. The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans.

    Science.gov (United States)

    Williams, Rebecca S; Kozan, Pinar; Samocha-Bonet, Dorit

    2016-05-01

    Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes. PMID:26363101

  13. The Relation between Photosynthesis, Respiration, and Crassulacean Acid Metabolism in Leaf Slices of Aloe arborescens Mill.

    Science.gov (United States)

    Denius, H R; Homann, P H

    1972-06-01

    Leaves and leaf slices from Aloe arborescens Mill. were used to study the interrelations between Crassulacean acid metabolism, photosynthesis, and respiration. Oxygen exchange of leaf slices was measured polarographically. It was found that the photosynthetic utilization of stored malic acid resulted in a net evolution of oxygen. This oxygen production, and the decrease in acid content of the leaf tissue, were completely inhibited by amytal, although the rate of respiratory oxygen uptake was hardly affected by the presence of this inhibitor of mitochondrial electron transport. Other poisons of respiration (cyanide) and of the tricarboxylic acid cycle (trifluoroacetate, 2-diethyl malonate) also were effective in preventing acid-dependent oxygen evolution. It is concluded that the mobilization of stored acids during light-dependent deacidification of the leaves depends on the operation of the tricarboxylic acid cycle and of the electron transport of the mitochondria.A comparison of enzyme activities in extracts from Aloe leaves and from other plants and studies of leaf anatomy and chloroplast morphology revealed typical characteristics of C(3)-, as well as C(4)-, plants in Aloe. PMID:16658075

  14. Metabolic Engineering of Yeast to Produce Fatty Acid-derived Biofuels: Bottlenecks and Solutions

    Directory of Open Access Journals (Sweden)

    Jiayuan eSheng

    2015-06-01

    Full Text Available Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles.

  15. Efficient fermentation of xylose to ethanol at high formic acid concentrations by metabolically engineered Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Hasunuma, Tomohisa; Yoshimura, Kazuya; Matsuda, Fumio [Kobe Univ., Hyogo (Japan). Organization of Advanced Science and Technology; Sung, Kyung-mo; Sanda, Tomoya; Kondo, Akihiko [Kobe Univ., Hyogo (Japan). Dept. of Chemical Science and Engineering

    2011-05-15

    Recombinant yeast strains highly tolerant to formic acid during xylose fermentation were constructed. Microarray analysis of xylose-fermenting Saccharomyces cerevisiae strain overexpressing endogenous xylulokinase in addition to xylose reductase and xylitol dehydrogenase from Pichia stipitis revealed that upregulation of formate dehydrogenase genes (FDH1 and FDH2) was one of the most prominent transcriptional events against excess formic acid. The quantification of formic acid in medium indicated that the innate activity of FDH was too weak to detoxify formic acid. To reinforce the capability for formic acid breakdown, the FDH1 gene was additionally overexpressed in the xylose-metabolizing recombinant yeast. This modification allowed the yeast to rapidly decompose excess formic acid. The yield and final ethanol concentration in the presence of 20 mM formic acid is as essentially same as that of control. The fermentation profile also indicated that the production of xylitol and glycerol, major by-products in xylose fermentation, was not affected by the upregulation of FDH activity. (orig.)

  16. On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism.

    Science.gov (United States)

    Ikon, Nikita; Ryan, Robert O

    2016-09-01

    3-methylglutaconic acid (3MGA)-uria occurs in numerous inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism. This organic acid arises from thioester cleavage of 3-methylglutaconyl CoA (3MG CoA), an intermediate in leucine catabolism. In individuals harboring mutations in 3MG CoA hydratase (i.e., primary 3MGA-uria), dietary leucine is the source of 3MGA. In secondary 3MGA-uria, however, no leucine metabolism defects have been reported. While others have suggested 3MGA arises from aberrant isoprenoid shunting from cytosol to mitochondria, an alternative route posits that 3MG CoA arises in three steps from mitochondrial acetyl CoA. Support for this biosynthetic route in IEMs is seen by its regulated occurrence in microorganisms. The fungus, Ustilago maydis, the myxobacterium, Myxococcus xanthus and the marine cyanobacterium, Lyngbya majuscule, generate 3MG CoA (or acyl carrier protein derivative) in the biosynthesis of iron chelating siderophores, iso-odd chain fatty acids and polyketide/nonribosomal peptide products, respectively. The existence of this biosynthetic machinery in these organisms supports a model wherein, under conditions of mitochondrial dysfunction, accumulation of acetyl CoA in the inner mitochondrial space as a result of inefficient fuel utilization drives de novo synthesis of 3MG CoA. Since humans lack the downstream biosynthetic capability of the organisms mentioned above, as 3MG CoA levels rise, thioester hydrolysis yields 3MGA, which is excreted in urine as unspent fuel. Understanding the metabolic origins of 3MGA may increase its utility as a biomarker. PMID:27091556

  17. CHARACTERIZATION OF CYPS IN THE METABOLISM OF ALL TRANS RETINOIC ACID BY LIVER MICROSOMES FROM MICE TREATED WITH CONAZOLES

    Science.gov (United States)

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may involve in conazole-...

  18. Independent fluctuations of malate and citrate in the CAM species Clusia hilariana Schltdl. under low light and high light in relation to photoprotection.

    Science.gov (United States)

    Miszalski, Zbigniew; Kornas, Andrzej; Rozpądek, Piotr; Fischer-Schliebs, Elke; Lüttge, Ulrich

    2013-03-15

    Clusia hilariana Schltdl. is described in literature as an obligate Crassulacean acid metabolism (CAM) species. In the present study we assessed the effect of irradiance with low light (LL, 200μmolm(-2)s(-1)) and high light (HL, 650-740μmolm(-2)s(-1)), on the interdependency of citrate and malate diurnal fluctuations. In plants grown at HL CAM-type oscillations of concentration of citrate and malate were obvious. However, at LL daily courses of both acids do not seem to indicate efficient utilization of these compounds as CO2 and NADPH sources. One week after transferring plants from LL to HL decarboxylation of malate was accelerated. Thus, in the CAM plant C. hilariana two independent rhythms of accumulation and decarboxylation of malate and citrate take place, which appear to be related to photosynthesis and respiration, respectively. Non photochemical quenching (NPQ) of photosystem II, especially well expressed during the evening hours was enhanced. Exposure to HL for 7 d activated oxidative stress protection mechanisms such as the interconversion of violaxanthin (V), antheraxanthin (A) and zeaxanthin (Z) (epoxydation/de-epoxydation) measured as epoxydation state (EPS). This was accompanied by a slight increase in the total amount of these pigments. However, all these changes were not observed in plants exposed to HL for only 2 d. Besides violaxanthin cycle components also lutein, which shows a small, but not significant increase, may be involved in dissipating excess light energy in C. hilariana.

  19. Characterization of Streptococcus oligofermentans sucrose metabolism demonstrates reduced pyruvic and lactic acid production

    Institute of Scientific and Technical Information of China (English)

    BAO Xu-dong; YUE Lin; GAO Xue-jun

    2011-01-01

    Background Streptococcus (S.) oligofermentans is a newly identified bacteria with a yet to be defined mechanism of sucrose metabolism that results in acid production.This study aimed to investigate the biochemical mechanisms of S.oligoferm-entans glucose metaolism.Methods The S.oligofermentans LMG21532,Lactobacillus (L.) fermentum 38 and the S.S.mutans UA140 were used to characterize sucrose metabolism by measuring lactate dehydrogenase (LDH) activity and lactic acid production.Continuous dynamics and high performance capillary electrophoresis were used to determine LDH activity and lactic acid production,respectively,from bacteria collected at 0,10 and 30 minutes after cultured in 10% sucrose.Results These analyses demonstrated that LDH activity of the three bacterial strains examined remained stable but significantly different throughout the sucrose fermentation process.The S.o/igofermentans LDH activity ((0.61±0.05) U/mg) was significantly lower than that of L.fermentum ((52.91+8.97) U/mg).In addition,the S.oligofermentans total lactate production ((0.048±0.021) mmol/L) was also significantly lower than that of L.fermentum ((0.958±0.201) mmol/L).Although the S.oligofermentans LDH production was almost double of that produced by S.mutans ((0.32±0.07) U/mg),lactic acid production was approximately one sixth that of S.mutans ((0.296±0.058) mmol/L).Additional tests examining pyruvic acid production (the LDH substrate) demonstrated that lactic acid concentrations correlated with pyruvic acid production.That is,pyruvic acid production by S.oligofermentans was undetectable following sucrose incubation,however,(0.074±t0.024) and (0.175±0.098) mmol/L pyruvic acid were produced by S.mutans and L.fermentum,respectively.Conclusion S.oligofermentans is incapable of fermenting carbohydrates to produce enough pyruvic acid,which results in reduced lactic acid production.

  20. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood ...

  1. Epidermal growth factor (EGF) sensitive phosphorylation of calmodulin (CAM) in A431 cell membrane

    International Nuclear Information System (INIS)

    A431, a transformed cell line, is known to contain a high concentration of EGF receptors (EGFR). Exogenous CAM, when combined with purified membrane from A431 is strongly phosphorylated in the presence of EGF. The EGF-dependent phosphorylation of CAM did not alter the normal profile of the A431 EGFR autophosphorylation, as demonstrated by SDS-PAGE and autoradiography. In addition to its EGF dependency, the presence of divalent cations is also critical for CAM phosphorylation. The presence of a divalent cation chelator, such as EGTA, caused a complete inhibition of CAM phosphorylation, which can be reversed with cations in the following order of effectiveness: Mg++ > Mn++ > Ca++. Divalent cations also break up CAM into four co-migrating bands as indicated by Coomassie Blue stained gels and the corresponding autoradiograms. Double antibody precipitation followed by phospho-amino acid analysis revealed that the EGF-sensitive CAM phosphorylation occurs exclusively on the serine residue. Using radioimmunoassay, purified A431 membrane was shown to contain a significant amount of endogenous CAM. The implications of the EGF-sensitive CAM phosphorylation are currently under investigation

  2. Role of phosphate in the central metabolism of two lactic acid bacteria-a comparative systems biology approach

    NARCIS (Netherlands)

    Levering, J.; Musters, M.W.J.M.; Bekker, M.; Bellomo, D.; Fiedler, T.; Vos, de W.M.; Hugenholtz, F.; Kreikemeyer, B.; Kummer, U.; Teusink, B.

    2012-01-01

    Lactic acid-producing bacteria survive in distinct environments, but show common metabolic characteristics. Here we studied the dynamic interactions of the central metabolism in Lactococcus lactis, extensively used as a starter culture in the dairy industry, and Streptococcus pyogenes, a human patho

  3. Role of phosphate in the central metabolism of two lactic acid bacteria - a comparative systems biology approach.

    NARCIS (Netherlands)

    J. Levering; M.W. Musters; M. Bekker; D. Bellomo; T. Fiedler; W.M. de Vos; J. Hugenholtz; B. Kreikemeyer; U. Kummer; B. Teusink

    2012-01-01

    Lactic acid-producing bacteria survive in distinct environments, but show common metabolic characteristics. Here we studied the dynamic interactions of the central metabolism in Lactococcus lactis, extensively used as a starter culture in the dairy industry, and Streptococcus pyogenes, a human patho

  4. Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

  5. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals.

    Science.gov (United States)

    Zhao, Linjing; Ni, Yan; Ma, Xiaojing; Zhao, Aihua; Bao, Yuqian; Liu, Jiajian; Chen, Tianlu; Xie, Guoxiang; Panee, Jun; Su, Mingming; Yu, Herbert; Wang, Congrong; Hu, Cheng; Jia, Weiping; Jia, Wei

    2016-01-01

    Increasing evidences support that metabolically healthy obese (MHO) is a transient state. However, little is known about the early markers associated with the development of metabolic abnormalities in MHO individuals. Serum free fatty acids (FFAs) profile is highlighted in its association with obesity-related insulin resistance, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). To examine the association of endogenous fatty acid metabolism with future development of metabolic abnormalities in MHO individuals, we retrospectively analyzed 24 [product FFA]/[precursor FFA] ratios in fasting sera and clinical data from 481 individuals who participated in three independent studies, including 131 metabolic healthy subjects who completed the 10-year longitudinal Shanghai Diabetes Study (SHDS), 312 subjects cross-sectionally sampled from the Shanghai Obesity Study (SHOS), and 38 subjects who completed an 8-week very low carbohydrate diet (VLCD) intervention study. Results showed that higher baseline level of oleic acid/stearic acid (OA/SA), and lower levels of stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with higher rate of MHO to MUO conversion in the longitudinal SHDS. Further, the finding was validated in the cross-sectional and interventional studies. This panel of FFA ratios could be used for identification and early intervention of at-risk obese individuals. PMID:27344992

  6. A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis

    Science.gov (United States)

    Dobbins, RL; O'Connor‐Semmes, RL; Young, MA

    2016-01-01

    A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. PMID:27537780

  7. Co-metabolic formation of substituted phenylacetic acids by styrene-degrading bacteria

    Directory of Open Access Journals (Sweden)

    Michel Oelschlägel

    2015-06-01

    The styrene-degrading strains Rhodococcus opacus 1CP, Pseudomonas fluorescens ST, and the novel isolates Sphingopyxis sp. Kp5.2 and Gordonia sp. CWB2 were investigated with respect to their applicability to co-metabolically produce substituted phenylacetic acids. Isolates were found to differ significantly in substrate tolerance and biotransformation yields. Especially, P. fluorescens ST was identified as a promising candidate for the production of several phenylacetic acids. The biotransformation of 4-chlorostyrene with cells of strain ST was shown to be stable over a period of more than 200 days and yielded about 38 mmolproduct gcelldryweight−1 after nearly 350 days. Moreover, 4-chloro-α-methylstyrene was predominantly converted to the (S-enantiomer of the acid with 40% enantiomeric excess.

  8. 科罗索酸的抗肿瘤作用及其对CAM和YS M血管生成的影响%Antitumor effect of corosolic acid and it’s impact on CAM and YSM angiogenesis

    Institute of Scientific and Technical Information of China (English)

    李标; 林伟民; 田树红; 李凡; 李富

    2014-01-01

    Objective To evaluate the antitumor effect of corosolic acid and its impact on CAM and YSM angiogenesis.Methods The effects of CRA on A549 proliferation was studied by MTT method in vitro.Tumor-bruden nude mice model were established by injecting A549 lung cancer cell marked with bioluminescent to nude mice,and the growth of tumor in mice were detected by IVIS small animal in vivo imaging system.Experiment of chicken embryos eggs are used to observe the role of drugs on CAMand YSMblood vessels. Results The value of IC50 of CRA for A549 in vitro was 26.8μg/mL.A tumor-burdened animal experiment results showed that the CRA to A549 solid tumor has a certain therapeutic effect.CAM and YSM blood vessels of chicken embryos eggs treated with CRA were decreased significantly than negative control group.Conclusion CRA has certain therapeutic effect for A549,which may be related to the inhibition of angiogenesis in tumor tissues.%目的:探究科罗索酸(corosolic acid,CRA)的抗肿瘤作用及其对鸡胚绒毛尿囊膜(chick chorioallantoic membrane,CAM)和卵黄囊膜(yolk sac membrane,YSM)血管生成的影响。方法 MTT法检测CRA对肺癌细胞A549增殖的影响。将生物发光标记的人肺癌细胞A549接种到裸小鼠体内,建立生物发光标记的裸小鼠荷瘤模型,采用IVIS小动物活体成像系统检测小鼠体内肿瘤生长情况。采用鸡胚孵化实验,观察CRA对CAM和YSM血管生成的影响。结果 CRA对A549增殖抑制的IC50值为26.8μg/mL。荷瘤动物试验结果表明:CRA对A549实体瘤有显著的抑制生长作用(P<0.01)。在鸡胚孵化实验中,CRA可明显降低CAM和YSM血管生成。结论 CRA对A549具有一定的治疗作用,其作用机制可能与抑制肿瘤组织中血管生成有关。

  9. Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

    Directory of Open Access Journals (Sweden)

    Pelletier Eric

    2010-10-01

    Full Text Available Abstract Background Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed. Results C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms. Conclusions Analysis of the C

  10. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    Directory of Open Access Journals (Sweden)

    Yasunori Konno

    Full Text Available Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4 is a G protein-coupled receptor (GPCR for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  11. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  12. Glyoxylate cycle and metabolism of organic acids in the scutellum of barley seeds during germination.

    Science.gov (United States)

    Ma, Zhenguo; Marsolais, Frédéric; Bernards, Mark A; Sumarah, Mark W; Bykova, Natalia V; Igamberdiev, Abir U

    2016-07-01

    During the developmental processes from dry seeds to seedling establishment, the glyoxylate cycle becomes active in the mobilization of stored oils in the scutellum of barley (Hordeum vulgare L.) seeds, as indicated by the activities of isocitrate lyase and malate synthase. The succinate produced is converted to carbohydrates via phosphoenolpyruvate carboxykinase and to amino acids via aminotransferases, while free organic acids may participate in acidifying the endosperm tissue, releasing stored starch into metabolism. The abundant organic acid in the scutellum was citrate, while malate concentration declined during the first three days of germination, and succinate concentration was low both in scutellum and endosperm. Malate was more abundant in endosperm tissue during the first three days of germination; before citrate became predominant, indicating that malate may be the main acid acidifying the endosperm. The operation of the glyoxylate cycle coincided with an increase in the ATP/ADP ratio, a buildup of H2O2 and changes in the redox state of ascorbate and glutathione. It is concluded that operation of the glyoxylate cycle in the scutellum of cereals may be important not only for conversion of fatty acids to carbohydrates, but also for the acidification of endosperm and amino acid synthesis. PMID:27181945

  13. Selected regulation of gastrointestinal acid-base secretion and tissue metabolism for the diamondback water snake and Burmese python.

    Science.gov (United States)

    Secor, Stephen M; Taylor, Josi R; Grosell, Martin

    2012-01-01

    Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI) performance with feeding and fasting; frequently feeding species modestly regulate intestinal function whereas infrequently feeding species rapidly upregulate and downregulate intestinal function with the start and completion of each meal, respectively. The downregulatory response with fasting for infrequently feeding snakes is hypothesized to be a selective attribute that reduces energy expenditure between meals. To ascertain the links between feeding habit, whole-animal metabolism, and GI function and metabolism, we measured preprandial and postprandial metabolic rates and gastric and intestinal acid-base secretion, epithelial conductance and oxygen consumption for the frequently feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding Burmese python (Python molurus). Independent of body mass, Burmese pythons possess a significantly lower standard metabolic rate and respond to feeding with a much larger metabolic response compared with water snakes. While fasting, pythons cease gastric acid and intestinal base secretion, both of which are stimulated with feeding. In contrast, fasted water snakes secreted gastric acid and intestinal base at rates similar to those of digesting snakes. We observed no difference between fasted and fed individuals for either species in gastric or intestinal transepithelial potential and conductance, with the exception of a significantly greater gastric transepithelial potential for fed pythons at the start of titration. Water snakes experienced no significant change in gastric or intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near-doubling of gastric metabolism and a tripling of intestinal metabolic rate. For fasted individuals, the metabolic rate of the stomach and small intestine was significantly lower for pythons than for water snakes. The fasting downregulation of digestive function for pythons is

  14. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Directory of Open Access Journals (Sweden)

    Albert Mas

    2014-01-01

    Full Text Available Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  15. Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders.

    Science.gov (United States)

    Verfaille, Christel J; Borgers, Marcel; van Steensel, Maurice A M

    2008-05-01

    Synthetic vitamin A derivatives, retinoids,have long been the mainstay of treatment for several disorders of keratinization, notably the ichthyoses and severe acne. Some forms of psoriasis also respond well. Their considerable power comes at a price. They have dose-limiting side effects and can be highly teratogenic, limiting their use in women of childbearing age.Thus, retinoids are used less often than their potential would warrant. However, the recent development of compounds that block the catabolism of endogenous vitamin A, called Retinioic Acid Metabolism Blocking Agents or RAMBAs, offers new possibilities. With these drugs, retinoid effects with less side effects and a reduction of the post-treatment teratogenicity period due to their favourable pharmacokinetic profile might be expected. In this review, we discuss how retinoids work, how they are metabolized and how RAMBAs influence this process. We also review the presently available data from clinical trials with RAMBAs. PMID:17941881

  16. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Science.gov (United States)

    Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements. PMID:24895623

  17. Metabolic engineering of Escherichia coli for production of mixed-acid fermentation end products

    Directory of Open Access Journals (Sweden)

    Andreas Hartmut Förster

    2014-05-01

    Full Text Available Mixed-acid fermentation end products have numerous applications in biotechnology. This is probably the main driving force for the development of multiple strains that are supposed to produce individual end products with high yields. The process of engineering Escherichia coli strains for applied production of ethanol, lactate, succinate, or acetate was initiated several decades ago and is still ongoing. This review follows the path of strain development from the general characteristics of aerobic versus anaerobic metabolism over the regulatory machinery that enables the different metabolic routes. Thereafter, major improvements for broadening the substrate spectrum of Escherichia coli towards cheap carbon sources like molasses or lignocellulose are highlighted before major routes of strain development for the production of ethanol, acetate, lactate and succinate are presented.

  18. Lysosomal acid lipase: At the crossroads of normal and atherogenic cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Joshua A Dubland

    2015-02-01

    Full Text Available Unregulated cellular uptake of apolipoprotein B-containing lipoproteins in the arterial intima leads to the formation of foam cells in atherosclerosis. Lysosomal acid lipase (LAL plays a crucial role in both lipoprotein lipid catabolism and excess lipid accumulation as it is the primary enzyme that hydrolyzes cholesteryl esters derived from both low density lipoprotein (LDL and modified forms of LDL. Evidence suggests that as atherosclerosis progresses, accumulation of excess free cholesterol in lysosomes leads to impairment of LAL activity, resulting in accumulation of cholesteryl esters in the lysosome as well as the cytosol in foam cells. Impaired metabolism and release of cholesterol from lysosomes can lead to downstream defects in ATP-binding cassette transporter A1 regulation, needed to offload excess cholesterol from plaque foam cells. This review focuses on the role LAL plays in normal cholesterol metabolism and how the associated changes in its enzymatic activity may ultimately contribute to atherosclerosis progression.

  19. Metabolic engineering of Pseudomonas fluorescens for the production of vanillin from ferulic acid.

    Science.gov (United States)

    Di Gioia, Diana; Luziatelli, Francesca; Negroni, Andrea; Ficca, Anna Grazia; Fava, Fabio; Ruzzi, Maurizio

    2011-12-20

    Vanillin is one of the most important flavors in the food industry and there is great interest in its production through biotechnological processes starting from natural substrates such as ferulic acid. Among bacteria, recombinant Escherichia coli strains are the most efficient vanillin producers, whereas Pseudomonas spp. strains, although possessing a broader metabolic versatility, rapidly metabolize various phenolic compounds including vanillin. In order to develop a robust Pseudomonas strain that can produce vanillin in high yields and at high productivity, the vanillin dehydrogenase (vdh)-encoding gene of Pseudomonas fluorescens BF13 strain was inactivated via targeted mutagenesis. The results demonstrated that engineered derivatives of strain BF13 accumulate vanillin if inactivation of vdh is associated with concurrent expression of structural genes for feruloyl-CoA synthetase (fcs) and hydratase/aldolase (ech) from a low-copy plasmid. The conversion of ferulic acid to vanillin was enhanced by optimization of growth conditions, growth phase and parameters of the bioconversion process. The developed strain produced up to 8.41 mM vanillin, which is the highest final titer of vanillin produced by a Pseudomonas strain to date and opens new perspectives in the use of bacterial biocatalysts for biotechnological production of vanillin from agro-industrial wastes which contain ferulic acid.

  20. Sodium glutamate and gamma-aminobutyric acid affect iron metabolism in the rat caudate putamen

    Institute of Scientific and Technical Information of China (English)

    Na Wang; Peng Guan; Fei Li; Yujian Fu; Xianglin Duan; Yanzhong Chang

    2010-01-01

    Glutamic acid and gamma-aminobutyric acid (GABA) influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 (DMT1) and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism, Results demonstrated that iron content and DMT1 non iron response element [DMT1 (-IRE)] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1(-IRE) expression was significantly reduced, but hephaestin expression was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMT1(-IRE) and decreasing hephaestin expression. In addition, GABA decreased DMT1(-IRE) expression in the caudate putamen.

  1. High Production of 3-Hydroxypropionic Acid in Klebsiella pneumoniae by Systematic Optimization of Glycerol Metabolism.

    Science.gov (United States)

    Li, Ying; Wang, Xi; Ge, Xizhen; Tian, Pingfang

    2016-01-01

    3-Hydroxypropionic acid (3-HP) is an important platform chemical proposed by the United States Department of Energy. 3-HP can be converted to a series of bulk chemicals. Biological production of 3-HP has made great progress in recent years. However, low yield of 3-HP restricts its commercialization. In this study, systematic optimization was conducted towards high-yield production of 3-HP in Klebsiella pneumoniae. We first investigated appropriate promoters for the key enzyme (aldehyde dehydrogenase, ALDH) in 3-HP biosynthesis, and found that IPTG-inducible tac promoter enabled overexpression of an endogenous ALDH (PuuC) in K. pneumoniae. We optimized the metabolic flux and found that blocking the synthesis of lactic acid and acetic acid significantly increased the production of 3-HP. Additionally, fermentation conditions were optimized and scaled-up cultivation were investigated. The highest 3-HP titer was observed at 83.8 g/L with a high conversion ratio of 54% on substrate glycerol. Furthermore, a flux distribution model of glycerol metabolism in K. pneumoniae was proposed based on in silico analysis. To our knowledge, this is the highest 3-HP production in K. pneumoniae. This work has significantly advanced biological production of 3-HP from renewable carbon sources. PMID:27230116

  2. Herbicide clomazone effects on δ-aminolevulinic acid activity and metabolic parameters in Cyprinus carpio.

    Science.gov (United States)

    Menezes, Charlene; Leitemperger, Jossiele; Murussi, Camila; Toni, Cândida; Araújo, Maria do Carmo Santos; Farias, Iria Luiza; Perazzo, Giselle Xavier; Barbosa, Nilda Vargas; Loro, Vania Lucia

    2014-04-01

    The objective of this study was to investigate δ-aminolevulinic acid (δ-ALA-D) activity and metabolic parameters of Cyprinus carpio exposed to clomazone herbicide. Fish were exposed 2.5, 5, 10 and 20 mg L(-1) of clomazone for 192 h. Results indicated that δ-ALA-D activity was decreased in the gills at concentrations of 5 and 10 mg L(-1). Liver glycogen increased, while muscle and gill glycogen levels decreased at 5, 10 and 20 mg L(-1). Glucose was increased in the gills and plasma. Lactate decreased in the gills and liver and increased in the muscle. Protein and amino acids levels increased in the liver and gills and decreased in the muscle. At a clomazone concentration of 20 mg L(-1), ammonia increased in the gills and muscle and decreased in the liver. The results indicated that the metabolic parameters of glycogen, lactate, protein and amino acids in liver, muscle and gills, blood glucose levels, and the enzyme δ-ALA-D in gills may be useful indicators of clomazone toxicity in carp.

  3. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    Directory of Open Access Journals (Sweden)

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  4. Characteristic metabolism of free amino acids in cetacean plasma: cluster analysis and comparison with mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Miyaji

    Full Text Available From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future.

  5. Comparative Transcriptome Analysis Reveals the Influence of Abscisic Acid on the Metabolism of Pigments, Ascorbic Acid and Folic Acid during Strawberry Fruit Ripening.

    Directory of Open Access Journals (Sweden)

    Dongdong Li

    Full Text Available A comprehensive investigation of abscisic acid (ABA biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of β-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and β-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient's biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA's role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future.

  6. Comparative Transcriptome Analysis Reveals the Influence of Abscisic Acid on the Metabolism of Pigments, Ascorbic Acid and Folic Acid during Strawberry Fruit Ripening.

    Science.gov (United States)

    Li, Dongdong; Li, Li; Luo, Zisheng; Mou, Wangshu; Mao, Linchun; Ying, Tiejin

    2015-01-01

    A comprehensive investigation of abscisic acid (ABA) biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker) treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA) and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of β-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and β-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient's biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA's role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future.

  7. Clinical aggressiveness of malignant gliomas is linked to augmented metabolism of amino acids.

    Science.gov (United States)

    Panosyan, Eduard H; Lasky, Joseph L; Lin, Henry J; Lai, Albert; Hai, Yang; Guo, Xiuqing; Quinn, Michael; Nelson, Stanley F; Cloughesy, Timothy F; Nghiemphu, P Leia

    2016-05-01

    Glutamine, glutamate, asparagine, and aspartate are involved in an enzyme-network that controls nitrogen metabolism. Branched-chain-amino-acid aminotransferase-1 (BCAT1) promotes proliferation of gliomas with wild-type IDH1 and is closely connected to the network. We hypothesized that metabolism of asparagine, glutamine, and branched-chain-amino-acids is associated with progression of malignant gliomas. Gene expression for asparagine synthetase (ASNS), glutaminase (GLS), and BCAT1 were analyzed in 164 gliomas from 156 patients [33-anaplastic gliomas (AG) and 131-glioblastomas (GBM), 64 of which were recurrent GBMs]. ASNS and GLS were twofold higher in GBMs versus AGs. BCAT1 was also higher in GBMs. ASNS expression was twofold higher in recurrent versus new GBMs. Five patients had serial samples: 4-showed higher ASNS and 3-higher GLS at recurrence. We analyzed grade and treatment in 4 groups: (1) low ASNS, GLS, and BCAT1 (n = 96); (2) low ASNS and GLS, but high BCAT1 (n = 26); (3) high ASNS or GLS, but low BCAT1 (n = 25); and (4) high ASNS or GLS and high BCAT1 (n = 17). Ninety-one  % of patients (29/32) with grade-III lesions were in group 1. In contrast, 95 % of patients (62/65) in groups 2-4 had GBMs. Treatment was similar in 4 groups (radiotherapy-80 %; temozolomide-30 %; other chemotherapy-50 %). High expression of ASNS, GLS, and BCAT1 were each associated with poor survival in the entire group. The combination of lower ASNS, GLS, and BCAT1 levels correlated with better survival for newly diagnosed GBMs (66 patients; P = 0.0039). Only tumors with lower enzymes showed improved outcome with temozolomide. IDH1(WT) gliomas had higher expression of these genes. Manipulation of amino acid metabolism in malignant gliomas may be further studied for therapeutics development. PMID:26922345

  8. One carbon metabolism in anaerobic bacteria: Regulation of carbon and electron flow during organic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Zeikus, J.G.; Jain, M.

    1993-12-31

    The project deals with understanding the fundamental biochemical mechanisms that physiologically control and regulate carbon and electron flow in anaerobic chemosynthetic bacteria that couple metabolism of single carbon compounds and hydrogen to the production of organic acids (formic, acetic, butyric, and succinic) or methane. The authors compare the regulation of carbon dioxide and hydrogen metabolism by fermentation, enzyme, and electron carrier analysis using Butyribacterium methylotrophicum, Anaeroblospirillum succiniciproducens, Methanosarcina barkeri, and a newly isolated tri-culture composed of a syntrophic butyrate degrader strain IB, Methanosarcina mazei and Methanobacterium formicicum as model systems. To understand the regulation of hydrogen metabolism during butyrate production or acetate degradation, hydrogenase activity in B. methylotrophicum or M. barkeri is measured in relation to growth substrate and pH; hydrogenase is purified and characterized to investigate number of hydrogenases; their localization and functions; and, their sequences are determined. To understand the mechanism for catabolic CO{sub 2} fixation to succinate the PEP carboxykinase enzyme and gene of A. succiniciproducens are purified and characterized. Genetically engineered strains of Escherichia coli containing the phosphoenolpyruvate (PEP) carboxykinase gene are examined for their ability to produce succinate in high yield. To understand the mechanism of fatty acid degradation by syntrophic acetogens during mixed culture methanogenesis formate and hydrogen production are characterized by radio tracer studies. It is intended that these studies provide strategies to improve anaerobic fermentations used for the production of organic acids or methane and, new basic understanding on catabolic CO{sub 2} fixation mechanisms and on the function of hydrogenase in anaerobic bacteria.

  9. Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation.

    Science.gov (United States)

    Kilberg, Michael S; Terada, Naohiro; Shan, Jixiu

    2016-07-01

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promise in regenerative medicine because of their ability to differentiate into all 3 primary germ layers. This review describes recent advances in the understanding of the link between the metabolism of ESCs/iPSCs and their maintenance/differentiation in the cell culture setting, with particular emphasis on amino acid (AA) metabolism. ESCs are endowed with unique metabolic features with regard to energy consumption, metabolite flux through particular pathways, and macromolecular synthesis. Therefore, nutrient availability has a strong influence on stem cell growth, self-renewal, and lineage specification, both in vivo and in vitro. Evidence from several laboratories has documented that self-renewal and differentiation of mouse ESCs are critically dependent on proline metabolism, with downstream metabolites possibly serving as signal molecules. Likewise, catabolism of either threonine (mouse) or methionine (human) is required for growth and differentiation of ESCs because these AAs serve as precursors for donor molecules used in histone methylation and acetylation. Epigenetic mechanisms are recognized as critical steps in differentiation, and AA metabolism in ESCs appears to modulate these epigenetic processes. Recent reports also document that, in vitro, the nutrient composition of the culture medium in which ESCs are differentiated into embryoid bodies can influence lineage specification, leading to enrichment of a specific cell type. Although research designed to direct tissue specification of differentiating embryoid bodies in culture is still in its infancy, early results indicate that manipulation of the nutrient milieu can promote or suppress the formation of specific cell lineages. PMID:27422515

  10. Metabolic engineering of Saccharomyces cerevisiae for production of carboxylic acids: current status and challenges.

    Science.gov (United States)

    Abbott, Derek A; Zelle, Rintze M; Pronk, Jack T; van Maris, Antonius J A

    2009-12-01

    To meet the demands of future generations for chemicals and energy and to reduce the environmental footprint of the chemical industry, alternatives for petrochemistry are required. Microbial conversion of renewable feedstocks has a huge potential for cleaner, sustainable industrial production of fuels and chemicals. Microbial production of organic acids is a promising approach for production of chemical building blocks that can replace their petrochemically derived equivalents. Although Saccharomyces cerevisiae does not naturally produce organic acids in large quantities, its robustness, pH tolerance, simple nutrient requirements and long history as an industrial workhorse make it an excellent candidate biocatalyst for such processes. Genetic engineering, along with evolution and selection, has been successfully used to divert carbon from ethanol, the natural endproduct of S. cerevisiae, to pyruvate. Further engineering, which included expression of heterologous enzymes and transporters, yielded strains capable of producing lactate and malate from pyruvate. Besides these metabolic engineering strategies, this review discusses the impact of transport and energetics as well as the tolerance towards these organic acids. In addition to recent progress in engineering S. cerevisiae for organic acid production, the key limitations and challenges are discussed in the context of sustainable industrial production of organic acids from renewable feedstocks. PMID:19566685

  11. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue.

    Science.gov (United States)

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males' subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  12. Gradient in the degree of Crassulacean acid metabolism within leaves of Kalanchoe daigremontiana.

    Science.gov (United States)

    Winter, K

    1987-09-01

    Leaves of the Crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perr., about 3.3 mm thick, showed higher rates of net CO2 exchange through the lower than through the upper surface during day and night, although the lower surface received only a small fraction of the light which was incident on the upper surface. Nocturnal acidification was more pronounced in cells from the lower than from the upper portion of leaves. The lower activity of the exposed side of these long-lived succulent leaves may be related to the potentially adverse effects of excessive light. PMID:24225791

  13. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism

    OpenAIRE

    Ross, A. Catharine; Zolfaghari, Reza

    2011-01-01

    The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family—CYP26A1, CYP26B1, and CYP26C1—is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1...

  14. From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria

    DEFF Research Database (Denmark)

    Gaspar, Paula; Carvalho, Ana L.; Vinga, Susana;

    2013-01-01

    The lactic acid bacteria (LAB) are a functionally related group of low-GC Gram-positive bacteria known essentially for their roles in bioprocessing of foods and animal feeds. Due to extensive industrial use and enormous economical value, LAB have been intensively studied and a large body...... of comprehensive data on their metabolism and genetics was generated throughout the years. This knowledge has been instrumental in the implementation of successful applications in the food industry, such as the selection of robust starter cultures with desired phenotypic traits. The advent of genomics, functional...

  15. Metabolism meets immunity: the role of free fatty acid receptors in the immune system

    OpenAIRE

    Alvarez-Curto, Elisa; Milligan, Graeme

    2016-01-01

    There are significant numbers of nutrient sensing G protein-coupled receptors (GPCRs) that can be found in cells of the immune system and in tissues that are involved in metabolic function, such as the pancreas or the intestinal epithelium. The family of free fatty acid receptors (FFAR1-4, GPR84), plus a few other metabolite sensing receptors (GPR109A, GPR91, GPR35) have been for this reason the focus of studies linking the effects of nutrients with immunological responses. A number of the be...

  16. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were...... incremental increase in hepatic glucose release rather than hepatic catabolism of amino acids....

  17. White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways

    Directory of Open Access Journals (Sweden)

    V. Barquissau

    2016-05-01

    Conclusions: Conversion of human white fat cells into brite adipocytes results in a major metabolic reprogramming inducing fatty acid anabolic and catabolic pathways. PDK4 redirects glucose from oxidation towards triglyceride synthesis and favors the use of fatty acids as energy source for uncoupling mitochondria.

  18. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice.

    Science.gov (United States)

    Liu, Jie; Lu, Yuan-Fu; Zhang, Youcai; Wu, Kai Connie; Fan, Fang; Klaassen, Curtis D

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential.

  19. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    Directory of Open Access Journals (Sweden)

    Siegmund Kimberly D

    2010-10-01

    Full Text Available Abstract Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  20. Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats

    Science.gov (United States)

    Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.

    1989-01-01

    The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.

  1. Abnormal Unsaturated Fatty Acid Metabolism in Cystic Fibrosis: Biochemical Mechanisms and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Adam C. Seegmiller

    2014-09-01

    Full Text Available Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely increased expression and activity of fatty acid desaturases. Among other effects, this drives metabolism of linoeate to arachidonate. Increased desaturase expression appears to be linked to cystic fibrosis mutations via stimulation of the AMP-activated protein kinase in the absence of functional CFTR protein. There is evidence that these abnormalities may contribute to disease pathophysiology by increasing production of eicosanoids, such as prostaglandins and leukotrienes, of which arachidonate is a key substrate. Understanding these underlying mechanisms provides key insights that could potentially impact the diagnosis, clinical monitoring, nutrition, and therapy of patients suffering from this deadly disease.

  2. Transport and Metabolism of the Endogenous Auxin Precursor lndole-3-Butyric Acid

    Institute of Scientific and Technical Information of China (English)

    Lucia C. Strader; Bonnie Bartel

    2011-01-01

    T Plant growth and morphogenesis depend on the levels and distribution of the plant hormone auxin. Plants tightly regulate cellular levels of the active auxin indole-3-acetic acid (IAA) through synthesis, inactivation, and transport. Although the transporters that move IAA into and out of cells are well characterized and play important roles in development, little is known about the transport of IAA precursors. In this review, we discuss the accumulating evidence suggesting that the IAA precursor indole-3-butyric acid (IBA) is transported independently of the characterized IAA transport machinery along with the recent identification of specific IBA efflux carriers and enzymes suggested to metabolize IBA. These studies have revealed important roles for IBA in maintaining IAA levels and distribution within the plant to support normal development.

  3. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Science.gov (United States)

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. PMID:26020623

  4. Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Poungrat Pakdeechote

    2014-01-01

    Full Text Available Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS induced by a high-carbohydrate, high-fat (HCHF diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α levels (p < 0.05. Plasma nitrate and nitrite (NOx were markedly high with upregulation of inducible nitric oxide synthase (iNOS expression, but dowregulation of endothelial nitric oxide synthase (eNOS expression (p < 0.05. Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05. In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  5. Metabolism of Terephthalic Acid and Its Effects on CYP4B1 Induction

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investgate the metabolism of terephthalic acid (TPA) in rats and its mechanism. Methods Metabolism was evaluated by incubating sodium terephthalate (NaTPA) with rat normal liver microsomes, or with microsomes pretreated by phenobarbital sodium, or with 3-methycholanthrene, or with diet control following a NADPH-generating system. The determination was performed by high performance liquid chromatography (HPLC), and the mutagenic activation was analyzed by umu tester strain Salmonella typhimurium NM2009. Expression of CYP4B 1 mRNA was detected by RT-PCR. Results The amount of NaTPA (12.5-200 μmol· L-1) detected by HPLC did not decrease in microsomes induced by NADPH-generating system. Incubation of TPA (0.025-0.1 mmol·L-1) with induced or noninduced liver microsomes in an NM2009 umu response system did not show any mutagenic activation. TPA exposure increased the expression of CYP4B 1 mRNA in rat liver, kidney, and bladder. Conclusion Lack of metabolism of TPA in liver and negative genotoxic data from NM2009 study are consistent with other previous short-term tests, suggesting that the carcinogenesis in TPA feeding animals is not directly interfered with TPA itself and/or its metabolites.

  6. Dynamic metabolic modelling of volatile fatty acids conversion to polyhydroxyalkanoates by a mixed microbial culture.

    Science.gov (United States)

    Pardelha, Filipa; Albuquerque, Maria G E; Reis, Maria A M; Oliveira, Rui; Dias, João M L

    2014-06-25

    In this work, we present a dynamic metabolic model that describes the uptake of complex mixtures of volatile fatty acids (VFA) and respective conversion into PHA by mixed microbial cultures (MMC). This model builds upon a previously published flux balance analysis model [1] that identified the minimization of TCA cycle activity as the key metabolic objective to predict PHA storage fluxes and respective composition. The model was calibrated either with experimental data of PHA production from fermented sugar cane molasses or from synthetic mixtures of VFA. All PHA production experiments were performed using a MMC selected with fermented sugar cane molasses under feast and famine regimen. The model was able to capture the process dynamics denoted by an excellent fit between experimental and computed time profiles of concentrations with the regression coefficients always above 0.92. The introduced VFA uptake regulatory factor reflects the decrease of acetyl-CoA and propionyl-CoA available to TCA cycle in conformity with the hypothesis that the minimization of TCA cycle is a key metabolic objective for MMC subjected to feast and famine regimen for the maximization of PHA production. PMID:23933561

  7. Effects of naphthenic acid exposure on development and liver metabolic processes in anuran tadpoles

    International Nuclear Information System (INIS)

    Naphthenic acids (NA) are used in a variety of commercial and industrial applications, and are primary toxic components of oil sands wastewater. We investigated developmental and metabolic responses of tadpoles exposed to sub-lethal concentrations of a commercial NA blend throughout development. We exposed Lithobates pipiens tadpoles to 1 and 2 mg/L NA for 75 days and monitored growth and development, condition factor, gonad and liver sizes, and levels of liver glucose, glycogen, lipids and cholesterol following exposure. NA decreased growth and development, significantly reduced glycogen stores and increased triglycerides, indicating disruption to processes associated with energy metabolism and hepatic glycolysis. Effects on liver function may explain reduced growth and delayed development observed in this and previous studies. Our data highlight the need for greater understanding of the mechanisms leading to hepatotoxicity in NA-exposed organisms, and indicate that strict guidelines may be needed for the release of NA into aquatic environments. -- Highlights: ► We exposed Lithobates pipiens tadpoles to 1–2 mg/L NA in the laboratory. ► We monitored survival, growth and development for 75 days. ► We measured liver glycogen, glucose, triglycerides, and cholesterol levels. ► NA significantly reduced growth and development compared to controls. ► NA significantly reduced glycogen levels and increased triglycerides. -- Leopard frog (Lithobates pipiens) tadpoles chronically exposed to sub-lethal NA concentrations (1–2 mg/L) suffered decreased growth and development and disruption to liver metabolic processes

  8. Essential amino-acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    As mentioned above, it was our intention to develop and test a simplified version of the protocol to assess amino acid metabolism in children. With the combined efforts of a team of experts in the field, a generic protocol was developed as a mandate of the first CRP held at Boston in the fall of 1993. During the beginning of 1994, the final version of such a protocol was released to all the participants of the CRP meeting and arrangements were made in order to apply it and assess its usefulness in the field setting. Therefore, we have shifted our activities to apply, assess and adapt the generic protocol. We are now testing the protocol in the field to establish the variability parameters in both between and within individuals. After testing and refining the protocol, with the help of other groups in developed countries, by validation and/or comparative studies, we would be in a better position to recommend it as a tool to study amino acid metabolism in children in developing countries, whether to describe some specific profiles or to evaluate nutrition interventions. 1 fig., 3 tabs

  9. Metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin

    Energy Technology Data Exchange (ETDEWEB)

    Uotila, P.; Paajanen, H.; Schalin, M.; Simberg, N.

    1983-10-01

    Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.4 and then at pH 3.5 and analysed by thin layer chromatography. Both aspirin and indomethacin inhibited dose dependently the formation of all identified prostaglandins, including PGF2 alpha, 6-keto-PGF1 alpha, PGE2 and PGD2. The rate of formation of some unidentified metabolites extracted at pH 7.4 and 3.5 was, however, not changed by aspirin or indomethacin. We have earlier reported that in isolated perfused hamster lungs the formation of all arachidonate metabolites is inhibited by both aspirin and indomethacin. As the present study indicates that in the microsomes of hamster lungs all metabolic pathways of arachidonic acid are not inhibited by aspirin or indomethacin, it is possible that in isolated tissues and in vivo aspirin-like drugs have some other inhibitory effects on arachidonate metabolism than the inhibition of the cyclo-oxygenase enzyme.

  10. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia.

    Science.gov (United States)

    Kaliannan, Kanakaraju; Wang, Bin; Li, Xiang-Yong; Kim, Kui-Jin; Kang, Jing X

    2015-06-11

    Metabolic endotoxemia, commonly derived from gut dysbiosis, is a primary cause of chronic low grade inflammation that underlies many chronic diseases. Here we show that mice fed a diet high in omega-6 fatty acids exhibit higher levels of metabolic endotoxemia and systemic low-grade inflammation, while transgenic conversion of tissue omega-6 to omega-3 fatty acids dramatically reduces endotoxemic and inflammatory status. These opposing effects of tissue omega-6 and omega-3 fatty acids can be eliminated by antibiotic treatment and animal co-housing, suggesting the involvement of the gut microbiota. Analysis of gut microbiota and fecal transfer revealed that elevated tissue omega-3 fatty acids enhance intestinal production and secretion of intestinal alkaline phosphatase (IAP), which induces changes in the gut bacteria composition resulting in decreased lipopolysaccharide production and gut permeability, and ultimately, reduced metabolic endotoxemia and inflammation. Our findings uncover an interaction between host tissue fatty acid composition and gut microbiota as a novel mechanism for the anti-inflammatory effect of omega-3 fatty acids. Given the excess of omega-6 and deficiency of omega-3 in the modern Western diet, the differential effects of tissue omega-6 and omega-3 fatty acids on gut microbiota and metabolic endotoxemia provide insight into the etiology and management of today's health epidemics.

  11. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia.

    Science.gov (United States)

    Kaliannan, Kanakaraju; Wang, Bin; Li, Xiang-Yong; Kim, Kui-Jin; Kang, Jing X

    2015-01-01

    Metabolic endotoxemia, commonly derived from gut dysbiosis, is a primary cause of chronic low grade inflammation that underlies many chronic diseases. Here we show that mice fed a diet high in omega-6 fatty acids exhibit higher levels of metabolic endotoxemia and systemic low-grade inflammation, while transgenic conversion of tissue omega-6 to omega-3 fatty acids dramatically reduces endotoxemic and inflammatory status. These opposing effects of tissue omega-6 and omega-3 fatty acids can be eliminated by antibiotic treatment and animal co-housing, suggesting the involvement of the gut microbiota. Analysis of gut microbiota and fecal transfer revealed that elevated tissue omega-3 fatty acids enhance intestinal production and secretion of intestinal alkaline phosphatase (IAP), which induces changes in the gut bacteria composition resulting in decreased lipopolysaccharide production and gut permeability, and ultimately, reduced metabolic endotoxemia and inflammation. Our findings uncover an interaction between host tissue fatty acid composition and gut microbiota as a novel mechanism for the anti-inflammatory effect of omega-3 fatty acids. Given the excess of omega-6 and deficiency of omega-3 in the modern Western diet, the differential effects of tissue omega-6 and omega-3 fatty acids on gut microbiota and metabolic endotoxemia provide insight into the etiology and management of today's health epidemics. PMID:26062993

  12. Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid.

    Science.gov (United States)

    Brown, Stephen H; Bashkirova, Lena; Berka, Randy; Chandler, Tyler; Doty, Tammy; McCall, Keith; McCulloch, Michael; McFarland, Sarah; Thompson, Sheryl; Yaver, Debbie; Berry, Alan

    2013-10-01

    Malic acid, a petroleum-derived C4-dicarboxylic acid that is used in the food and beverage industries, is also produced by a number of microorganisms that follow a variety of metabolic routes. Several members of the genus Aspergillus utilize a two-step cytosolic pathway from pyruvate to malate known as the reductive tricarboxylic acid (rTCA) pathway. This simple and efficient pathway has a maximum theoretical yield of 2 mol malate/mol glucose when the starting pyruvate originates from glycolysis. Production of malic acid by Aspergillus oryzae NRRL 3488 was first improved by overexpression of a native C4-dicarboxylate transporter, leading to a greater than twofold increase in the rate of malate production. Overexpression of the native cytosolic alleles of pyruvate carboxylase and malate dehydrogenase, comprising the rTCA pathway, in conjunction with the transporter resulted in an additional 27 % increase in malate production rate. A strain overexpressing all three genes achieved a malate titer of 154 g/L in 164 h, corresponding to a production rate of 0.94 g/L/h, with an associated yield on glucose of 1.38 mol/mol (69 % of the theoretical maximum). This rate of malate production is the highest reported for any microbial system.

  13. Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism

    Science.gov (United States)

    Cao, Weijia; Ma, Weichao; Wang, Xin; Zhang, Bowen; Cao, Xun; Chen, Kequan; Li, Yan; Ouyang, Pingkai

    2016-01-01

    Microbial biosynthesis of pinocembrin is of great interest in the area of drug research and human healthcare. Here we found that the accumulation of the pathway intermediate cinnamic acid adversely affected pinocembrin production. Hence, a stepwise metabolic engineering strategy was carried out aimed at eliminating this pathway bottleneck and increasing pinocembrin production. The screening of gene source and the optimization of gene expression was first employed to regulate the synthetic pathway of cinnamic acid, which showed a 3.53-fold increase in pinocembrin production (7.76 mg/L) occurred with the alleviation of cinnamic acid accumulation in the engineered E. coli. Then, the downstream pathway that consuming cinnamic acid was optimized by the site-directed mutagenesis of chalcone synthase and cofactor engineering. S165M mutant of chalcone synthase could efficiently improve the pinocembrin production, and allowed the product titer of pinocembrin increased to 40.05 mg/L coupled with the malonyl-CoA engineering. With a two-phase pH fermentation strategy, the cultivation of the optimized strain resulted in a final pinocembrin titer of 67.81 mg/L. The results and engineering strategies demonstrated here would hold promise for the titer improvement of other flavonoids. PMID:27586788

  14. Homofermentative production of D-lactic acid from sucrose by a metabolically engineered Escherichia coli.

    Science.gov (United States)

    Wang, Yongze; Tian, Tian; Zhao, Jinfang; Wang, Jinhua; Yan, Tao; Xu, Liyuan; Liu, Zao; Garza, Erin; Iverson, Andrew; Manow, Ryan; Finan, Chris; Zhou, Shengde

    2012-11-01

    Escherichia coli W, a sucrose-positive strain, was engineered for the homofermentative production of D-lactic acid through chromosomal deletion of the competing fermentative pathway genes (adhE, frdABCD, pta, pflB, aldA) and the repressor gene (cscR) of the sucrose operon, and metabolic evolution for improved anaerobic cell growth. The resulting strain, HBUT-D, efficiently fermented 100 g sucrose l(-1) into 85 g D-lactic acid l(-1) in 72-84 h in mineral salts medium with a volumetric productivity of ~1 g l(-1) h(-1), a product yield of 85 % and D-lactic acid optical purity of 98.3 %, and with a minor by-product of 4 g acetate l(-1). HBUT-D thus has great potential for production of D-lactic acid using an inexpensive substrate, such as sugar cane and/or beet molasses, which are primarily composed of sucrose. PMID:22791225

  15. The central role of chloride in the metabolic acid-base changes in canine parvoviral enteritis.

    Science.gov (United States)

    Burchell, Richard K; Schoeman, Johan P; Leisewitz, Andrew L

    2014-04-01

    The acid-base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid-base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid-base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson-Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid-base changes, according to the SIM, was chloride (Penteritis are multifactorial and complex, with the SIM providing information in terms of the origin of these changes.

  16. Dietary fatty acids affecting hepatic metabolism and atherosclerosis - mechanisms unravelled using a proteomics approach

    Directory of Open Access Journals (Sweden)

    Rodríguez Gutiérrez, Guillermo

    2009-03-01

    Full Text Available Dietary fatty acids play an important role in the aetiology of coronary heart disease. The effects of dietary fatty acids on lipoprotein metabolism are well described, but additional or alternative mechanisms relating to potential influence on coronary heart disease are not known. This review describes how proteomics techniques have been used to identify proteins that are differentially regulated by dietary fatty acids. Such proteins may reveal pathways by which dietary fatty acids influence disease risk.Los ácidos grasos de la dieta cumplen un importante papel en la etiología de las enfermedades coronarias. A pesar de estar bien descrito el efecto de dichos ácidos grasos sobre el metabolismo lipoproteíco, no se conocen mecanismos alternativos que relacionen su influencia sobre posibles enfermedades coronarias. En esta revisión se describe el uso de técnicas proteómicas para la identificación de proteínas diferencialmente reguladas por dichos ácidos grasos. Tales proteínas pueden revelar rutas metabólicas implicadas en el riesgo de enfermedades y reguladas por los ácidos grasos de la dieta.

  17. Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism

    Science.gov (United States)

    Cao, Weijia; Ma, Weichao; Wang, Xin; Zhang, Bowen; Cao, Xun; Chen, Kequan; Li, Yan; Ouyang, Pingkai

    2016-09-01

    Microbial biosynthesis of pinocembrin is of great interest in the area of drug research and human healthcare. Here we found that the accumulation of the pathway intermediate cinnamic acid adversely affected pinocembrin production. Hence, a stepwise metabolic engineering strategy was carried out aimed at eliminating this pathway bottleneck and increasing pinocembrin production. The screening of gene source and the optimization of gene expression was first employed to regulate the synthetic pathway of cinnamic acid, which showed a 3.53-fold increase in pinocembrin production (7.76 mg/L) occurred with the alleviation of cinnamic acid accumulation in the engineered E. coli. Then, the downstream pathway that consuming cinnamic acid was optimized by the site-directed mutagenesis of chalcone synthase and cofactor engineering. S165M mutant of chalcone synthase could efficiently improve the pinocembrin production, and allowed the product titer of pinocembrin increased to 40.05 mg/L coupled with the malonyl-CoA engineering. With a two-phase pH fermentation strategy, the cultivation of the optimized strain resulted in a final pinocembrin titer of 67.81 mg/L. The results and engineering strategies demonstrated here would hold promise for the titer improvement of other flavonoids.

  18. Amino acid metabolism in the kidneys of genetic and nutritionally obese rats.

    Science.gov (United States)

    Herrero, M C; Remesar, X; Bladé, C; Arola, L

    1997-06-01

    The ability of the kidney to take up and/or release amino acids has been determined in two models of obesity in Zucker rats, one genetic and the other nutritional (diet-obese). There was a noticeable increase in gluconeogenic amino acids in the arterial blood of diet-obese animals whereas the genetically obese rats showed small variations in the levels of these amino acids. There were significant decreases in renal Gly and Ser, only in the genetically obese rats. Genetically obese animals showed an increase in Glutamine synthetase activity. The uptake and/or release of amino acids showed important variations between the groups. The diet-obese group exhibited greater variation, since this group took up Glu, Ala, Gy, Phe and Citrulline and released Gln, Ser, Arg and Tyr. Genetically obese rats took up Gln, His and Taurine and released Ser. These different patterns may be related to variations in the whole body metabolic rate, since the diet-obese group was more active than the genetically obese group.

  19. Simultaneous determination of C2-C22 non-esterified fatty acids and other metabolically relevant carboxylic acids in biological material by gas chromatography of their benzyl esters.

    Science.gov (United States)

    Schatowitz, B; Gercken, G

    1988-03-18

    A method for the simultaneous determination of non-esterified short-, medium- and long-chain fatty acids and other types of metabolically relevant carboxylic acids such as hydroxy, keto, aromatic and dicarboxylic acids in biological material by capillary gas chromatography of benzyl ester derivatives is described. Sample preparation avoiding incomplete isolation of carboxylic acids consisted of deproteinization and extraction with ethanol, fixation of carboxylic acids as carboxylates, removal of interfering compounds such as neutral lipids by hexane extraction and amino acids, acyl carnitines and other cations by cation-exchange chromatography, derivatization of keto groups of ketocarboxylic acids into O-methyl oximes and benzyl ester formation by reaction of the potassium carboxylates with benzyl bromide via crown ether catalysis. The sample preparation conditions were investigated, showing the usefulness of this method for quantitative determinations. Chromatograms obtained from human serum, human urine and rat heart ventricle and concentrations of carboxylic acids in these specimens are presented. PMID:3372640

  20. Relationship between Sialic acid and metabolic variables in Indian type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Nayak B Shivananda

    2005-08-01

    Full Text Available Abstract Background Plasma sialic acid is a marker of the acute phase response. Objective is to study the relationship between sialic acid relationship with metabolic variables in Indian type 2 diabetes with and without microvascular complications. Research design and Methods Fasting Venous blood samples were taken from 200 subjects of which 50 were of diabetes mellitus (DM and nephropathy patients, 50 patients with type 2 diabetes and retinopathy, 50 patients with type 2 diabetes without any complications and 50 healthy individuals without diabetes. The Indian subject's aged 15–60 years with type 2 diabetes were recruited for the study. Simultaneously urine samples were also collected from each of the subjects. All the blood samples were analyzed for total cholesterol, triglyceride (TG, low-density lipoprotein (LDL, high-density lipoprotein (HDL, fasting and postprandial glucose on fully automated analyzer. Serum and urine sialic acid along with microalbumin levels were also estimated. Results There was a significantly increasing trend of plasma and urine sialic acid with severity of nephropathy (P 1c, serum triglyceride and cholesterol concentrations, waist-to-hip ratio and hypertension. Significant correlations were found between sialic acid concentration and cardiovascular risk factors like LDL and TG in the diabetic subjects. Conclusion The main finding of this study is that elevated serum and urinary sialic acid and microalbumin concentrations were strongly related to the presence of microvascular complications like diabetic nephropathy and retinopathy and cardiovascular risk factors in Indian type 2 diabetic subjects. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

  1. Does genetic variation in the Δ6-desaturase promoter modify the association between α-linolenic acid and the prevalence of metabolic syndrome?123

    OpenAIRE

    Truong, Hong; DiBello, Julia R; Ruiz-Narvaez, Edward; Kraft, Peter; Campos, Hannia; Baylin, Ana

    2009-01-01

    Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with protection against components of the metabolic syndrome, but the role of α-linolenic acid (ALA), the metabolic precursor of EPA and DHA, has not been studied. The Δ6-desaturase enzyme converts ALA into EPA and DHA, and genetic variation in the Δ6-desaturase gene (FADS2) may affect this conversion.

  2. Metabolic regulation of trisporic acid on Blakeslea trispora revealed by a GC-MS-based metabolomic approach.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    Full Text Available The zygomycete Blakeslea trispora is used commercially as natural source of â-carotene. Trisporic acid (TA is secreted from the mycelium of B. trispora during mating between heterothallic strains and is considered as a mediator of the regulation of mating processes and an enhancer of carotene biosynthesis. Gas chromatography-mass spectrometry and multivariate analysis were employed to investigate TA-associated intracellular biochemical changes in B. trispora. By principal component analysis, the differential metabolites discriminating the control groups from the TA-treated groups were found, which were also confirmed by the subsequent hierarchical cluster analysis. The results indicate that TA is a global regulator and its main effects at the metabolic level are reflected on the content changes in several fatty acids, carbohydrates, and amino acids. The carbon metabolism and fatty acids synthesis are sensitive to TA addition. Glycerol, glutamine, and ã-aminobutyrate might play important roles in the regulation of TA. Complemented by two-dimensional electrophoresis, the results indicate that the actions of TA at the metabolic level involve multiple metabolic processes, such as glycolysis and the bypass of the classical tricarboxylic acid cycle. These results reveal that the metabolomics strategy is a powerful tool to gain insight into the mechanism of a microorganism's cellular response to signal inducers at the metabolic level.

  3. Hazmat Cam Wireless Video System

    Energy Technology Data Exchange (ETDEWEB)

    Kevin L. Young

    2006-02-01

    This paper describes the Hazmat Cam Wireless Video System and its application to emergency response involving chemical, biological or radiological contamination. The Idaho National Laboratory designed the Hazmat Cam Wireless Video System to assist the National Guard Weapons of Mass Destruction - Civil Support Teams during their mission of emergency response to incidents involving weapons of mass destruction. The lightweight, handheld camera transmits encrypted, real-time video from inside a contaminated area, or hot-zone, to a command post located a safe distance away. The system includes a small wireless video camera, a true-diversity receiver, viewing console, and an optional extension link that allows the command post to be placed up to five miles from danger. It can be fully deployed by one person in a standalone configuration in less than 10 minutes. The complete system is battery powered. Each rechargeable camera battery powers the camera for 3 hours with the receiver and video monitor battery lasting 22 hours on a single charge. The camera transmits encrypted, low frequency analog video signals to a true-diversity receiver with three antennas. This unique combination of encryption and transmission technologies delivers encrypted, interference-free images to the command post under conditions where other wireless systems fail. The lightweight camera is completely waterproof for quick and easy decontamination after use. The Hazmat Cam Wireless Video System is currently being used by several National Guard Teams, the US Army, and by fire fighters. The system has been proven to greatly enhance situational awareness during the crucial, initial phase of a hazardous response allowing commanders to make better, faster, safer decisions.

  4. CAD/CAM-prosessin kuvaus

    OpenAIRE

    Aho, Arto

    2014-01-01

    Työssä selvitettiin CAD/CAM-prosessin toiminta ja datan liikkuminen eri järjestelmien välillä. Teoriassa perehdyttiin tuotetietojen ja muutostenhallintaan sekä järjestelmien integrointiin. Siemens PLM -järjestelmästä esitellään valmistusprosessin suunnitteluun ja hallintaan tarkoitettuja sovelluksia. Työssä käsitellään muutoksenhallintaa järjestelmien välillä sekä nopeiden muutosten aikaansaamat hyödyt prosessissa ja integraation tuomat edut virheiden ja kustannusten vähentämisessä. Työssä...

  5. CAD/CAM-ohjelmiston valinta

    OpenAIRE

    Heino, Sanna

    2011-01-01

    Opinnäytetyön toimeksianto tuli Helasteel Oy:ltä. Työn sisältö koostuu sopivan CAM-ohjelmiston etsimisestä Helasteelille sekä niiden perusteiden selvittämisestä, jotka vaikuttavat ohjelmiston valintaan. Kolmea eri ohjelmistotoimittajaa pyydettiin esittelemään tuotteitaan Helasteelille. Näistä ohjelmistoista valittiin sopivin yrityksen työstämät kappaleet ja tuotanto huomioon ottaen. Prosessin jälkeen päädyttiin Wincam-ohjelmistoon, joka vastasi parhaiten Helasteelin vaatimuksiin niin omina...

  6. The impact of acetate metabolism on yeast fermentative performance and wine quality: reduction of volatile acidity of grape musts and wines

    OpenAIRE

    Moura, A. Vilela; Schuller, Dorit Elisabeth; Faia, A. Mendes; Silva, Rui D.; Chaves, S R; Sousa, Maria João; Côrte-Real, Manuela

    2011-01-01

    Acetic acid is the main component of the volatile acidity of grape musts and wines. It can be formed as a byproduct of alcoholic fermentation or as a product of the metabolism of acetic and lactic acid bacteria, which can metabolize residual sugars to increase volatile acidity. Acetic acid has a negative impact on yeast fermentative performance and affects the quality of certain types of wine when present above a given concentration. In this minireview, we present an o...

  7. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

    Directory of Open Access Journals (Sweden)

    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  8. Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals.

    Science.gov (United States)

    Bugaut, M

    1987-01-01

    Short chain fatty acids (SCFA) also named volatile fatty acids, mainly acetate, propionate and butyrate, are the major end-products of the microbial digestion of carbohydrates in the alimentary canal. The highest concentrations are observed in the forestomach of the ruminants and in the large intestine (caecum and colon) of all the mammals. Butyrate and caproate released by action of gastric lipase on bovine milk triacylglycerols ingested by preruminants or infants are of nutritional importance too. Both squamous stratified mucosa of rumen and columnar simple epithelium of intestine absorb readily SCFA. The mechanisms of SCFA absorption are incompletely known. Passive diffusion of the unionized form across the cell membrane is currently admitted. In the lumen, the necessary protonation of SCFA anions could come first from the hydration of CO2. The ubiquitous cell membrane process of Na+-H+ exchange can also supply luminal protons. Evidence for an acid microclimate (pH = 5.8-6.8) suitable for SCFA-protonation on the surface of the intestinal lining has been provided recently. This microclimate would be generated by an epithelial secretion of H+ ions and would be protected by the mucus coating from the variable pH of luminal contents. Part of the absorbed SCFA does not reach plasma because it is metabolized in the gastrointestinal wall. Acetate incorporation in mucosal higher lipids is well-known. However, the preponderant metabolic pathway for all the SCFA is catabolism to CO2 except in the rumen wall where about 80% of butyrate is converted to ketone bodies which afterwards flow into bloodstream. Thus, SCFA are an important energy source for the gut mucosa itself.

  9. Effects of supplementation with 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester on splanchnic amino acid metabolism and essential amino acid mobilization in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Dalbach, Kristine Foged; Larsen, Mogens; Raun, Birgitte Marie Løvendahl;

    2011-01-01

    The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated by differ...... the first 29 DIM. Extra-splanchnic EAA mobilization can be crucial to sustain milk protein yield in the postpartum transition period and HMBi is a fast-working Met source that can improve Met status of postpartum transition cows.......The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated...... by difference: EAA excretion in milk protein − net portal absorption of EAA or net splanchnic release of EAA. Eight Holstein cows fitted with permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery in the dry period preceding second parturition were used...

  10. The Effect of Rumen Acid Load on Postpartum Performance and Blood Metabolic Responses in Transition Holstein Cows

    OpenAIRE

    S. D. Mesgaran; Vakili, A.; A. H. Moosavi; G. Koolabadi

    2011-01-01

    Problem statement: The transition period is the most stressful time in the production cycle of a dairy cow because of depressed feed intake, endocrine and metabolic changes at parturition. The aim was to determine the effect of rumen acid load on postpartum performance and metabolic parameters in transition Holstein cows. Approach: The Acidogenicity Values (AV) of the diets were determined using an In-vitro essay. Thirty late pregnant multiparous Holstein cows with the ave...

  11. Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

    Directory of Open Access Journals (Sweden)

    Hauenschild A

    2003-11-01

    Full Text Available Abstract Background The amount and quality of dietary fatty acids can modulate the fat metabolism. Objective This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA, which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes. Design In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30 of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile. Results The plasma triacylglycerol (p Conclusion Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.

  12. Thyroid Disease and Complementary and Alternative Medicine (CAM)

    Science.gov (United States)

    ... to Donate Thyroid Disease and Complementary and Alternative Medicine (CAM) WHAT IS A THYROID NODULE? The term ... type of evaluation. WHAT IS COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)? Complementary and Alternative Medicine (CAM) is defined ...

  13. Differences in phosphatidic acid signalling and metabolism between ABA and GA treatments of barley aleurone cells.

    Science.gov (United States)

    Villasuso, Ana Laura; Di Palma, Maria A; Aveldaño, Marta; Pasquaré, Susana J; Racagni, Graciela; Giusto, Norma M; Machado, Estela E

    2013-04-01

    Phosphatidic acid (PA) is the common lipid product in abscisic acid (ABA) and gibberellic acid (GA) response. In this work we investigated the lipid metabolism in response to both hormones. We could detect an in vivo phospholipase D activity (PLD, EC 3.1.4.4). This PLD produced [(32)P]PA (phosphatidic acid) rapidly (minutes) in the presence of ABA, confirming PA involvement in signal transduction, and transiently, indicating rapid PA removal after generation. The presence of PA removal by phosphatidate phosphatase 1 and 2 isoforms (E.C. 3.1.3.4) was verified in isolated aleurone membranes in vitro, the former but not the latter being specifically responsive to the presence of GA or ABA. The in vitro DGPP phosphatase activity was not modified by short time incubation with GA or ABA while the in vitro PA kinase - that allows the production of 18:2-DGPP from 18:2-PA - is stimulated by ABA. The long term effects (24 h) of ABA or GA on lipid and fatty acid composition of aleurone layer cells were then investigated. An increase in PC and, to a lesser extent, in PE levels is the consequence of both hormone treatments. ABA, in aleurone layer cells, specifically activates a PLD whose product, PA, could be the substrate of PAP1 and/or PAK activities. Neither PLD nor PAK activation can be monitored by GA treatment. The increase in PAP1 activity monitored after ABA or GA treatment might participate in the increase in PC level observed after 24 h hormone incubation.

  14. Uptake and metabolic effects of salicylic acid on the pulvinar motor cells of Mimosa pudica L.

    Science.gov (United States)

    Dédaldéchamp, Fabienne; Saeedi, Saed; Fleurat-Lessard, Pierrette; Roblin, Gabriel

    2014-01-01

    In this paper, the salicylic acid (o-hydroxy benzoic acid) (SA) uptake by the pulvinar tissues of Mimosa pudica L. pulvini was shown to be strongly pH-dependent, increasing with acidity of the assay medium. This uptake was performed according to a unique affinity system (K(m) = 5.9 mM, V(m) = 526 pmol mgDW(-1)) in the concentration range of 0.1-5 mM. The uptake rate increased with increasing temperature (5-35 °C) and was inhibited following treatment with sodium azide (NaN3) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), suggesting the involvement of an active component. Treatment with p-chloromercuribenzenesulfonic acid (PCMBS) did not modify the uptake, indicating that external thiol groups were not necessary. KCl, which induced membrane depolarization had no significant effect, and fusicoccin (FC), which hyperpolarized cell membrane, stimulated the uptake, suggesting that the pH component of the proton motive force was likely a driving force. These data suggest that the SA uptake by the pulvinar tissues may be driven by two components: an ion-trap mechanism playing a pivotal role and a putative carrier-mediated mechanism. Unlike other benzoic acid derivatives acting as classical respiration inhibitors (NaN3 and KCN), SA modified the pulvinar cell metabolism by increasing the respiration rate similar to CCCP and 2,4-dinitrophenol (DNP). Furthermore, SA inhibited the osmoregulated seismonastic reaction in a pH dependent manner and induced characteristic damage to the ultrastructural features of the pulvinar motor cells, particularly at the mitochondrial level.

  15. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Directory of Open Access Journals (Sweden)

    Manuel A. Fernández-Rojo

    2013-07-01

    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  16. Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes.

    Science.gov (United States)

    Grenier-Larouche, T; Labbé, S M; Noll, C; Richard, D; Carpentier, A C

    2012-12-01

    Type 2 diabetes (T2D) is characterized by a general dysregulation of postprandial energy substrate partitioning. Although classically described in regard to glucose metabolism, it is now evident that metabolic inflexibility of plasma lipid fluxes is also present in T2D. The organ that is most importantly involved in the latter metabolic defect is the white adipose tissue (WAT). Both catecholamine-induced nonesterified fatty acid mobilization and insulin-stimulated storage of meal fatty acids are impaired in many WAT depots of insulin-resistant individuals. Novel molecular imaging techniques now demonstrate that these defects are linked to increased dietary fatty acid fluxes toward lean organs and myocardial dysfunction in humans. Recent findings also demonstrate functional abnormalities of brown adipose tissues in T2D, thus suggesting that a generalized adipose tissue dysregulation of energy storage and dissipation may be at play in the development of lean tissue energy overload and lipotoxicity. PMID:27152152

  17. Amino acid metabolism in the human fetus at term: leucine, valine, and methionine kinetics.

    Science.gov (United States)

    van den Akker, Chris H P; Schierbeek, Henk; Minderman, Gardi; Vermes, Andras; Schoonderwaldt, Ernst M; Duvekot, Johannes J; Steegers, Eric A P; van Goudoever, Johannes B

    2011-12-01

    Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.

  18. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.

    Science.gov (United States)

    Yan, Yiqing; Jiang, Wei; Spinetti, Thibaud; Tardivel, Aubry; Castillo, Rosa; Bourquin, Carole; Guarda, Greta; Tian, Zhigang; Tschopp, Jurg; Zhou, Rongbin

    2013-06-27

    Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases. PMID:23809162

  19. Metabolism meets immunity: The role of free fatty acid receptors in the immune system.

    Science.gov (United States)

    Alvarez-Curto, Elisa; Milligan, Graeme

    2016-08-15

    There are significant numbers of nutrient sensing G protein-coupled receptors (GPCRs) that can be found in cells of the immune system and in tissues that are involved in metabolic function, such as the pancreas or the intestinal epithelium. The family of free fatty acid receptors (FFAR1-4, GPR84), plus a few other metabolite sensing receptors (GPR109A, GPR91, GPR35) have been for this reason the focus of studies linking the effects of nutrients with immunological responses. A number of the beneficial anti-inflammatory effects credited to dietary fats such as omega-3 fatty acids are attributed to their actions on FFAR4.This might play an important protective role in the development of obesity, insulin resistance or asthma. The role of the short-chain fatty acids resulting from fermentation of fibre by the intestinal microbiota in regulating acute inflammatory responses is also discussed. Finally we assess the therapeutic potential of this family of receptors to treat pathologies where inflammation is a major factor such as type 2 diabetes, whether by the use of novel synthetic molecules or by the modulation of the individual's diet. PMID:27002183

  20. Metabolic engineering of Pseudomonas putida for production of docosahexaenoic acid based on a myxobacterial PUFA synthase.

    Science.gov (United States)

    Gemperlein, Katja; Zipf, Gregor; Bernauer, Hubert S; Müller, Rolf; Wenzel, Silke C

    2016-01-01

    Long-chain polyunsaturated fatty acids (LC-PUFAs) can be produced de novo via polyketide synthase-like enzymes known as PUFA synthases, which are encoded by pfa biosynthetic gene clusters originally discovered from marine microorganisms. Recently similar gene clusters were detected and characterized in terrestrial myxobacteria revealing several striking differences. As the identified myxobacterial producers are difficult to handle genetically and grow very slowly we aimed to establish heterologous expression platforms for myxobacterial PUFA synthases. Here we report the heterologous expression of the pfa gene cluster from Aetherobacter fasciculatus (SBSr002) in the phylogenetically distant model host bacteria Escherichia coli and Pseudomonas putida. The latter host turned out to be the more promising PUFA producer revealing higher production rates of n-6 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). After several rounds of genetic engineering of expression plasmids combined with metabolic engineering of P. putida, DHA production yields were eventually increased more than threefold. Additionally, we applied synthetic biology approaches to redesign and construct artificial versions of the A. fasciculatus pfa gene cluster, which to the best of our knowledge represents the first example of a polyketide-like biosynthetic gene cluster modulated and synthesized for P. putida. Combination with the engineering efforts described above led to a further increase in LC-PUFA production yields. The established production platform based on synthetic DNA now sets the stage for flexible engineering of the complex PUFA synthase. PMID:26617065

  1. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    Science.gov (United States)

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  2. Metabolic reprogramming through fatty acid transport protein 1 (FATP1 regulates macrophage inflammatory potential and adipose inflammation

    Directory of Open Access Journals (Sweden)

    Amy R. Johnson

    2016-07-01

    Conclusion: Our findings provide evidence that FATP1 is a novel regulator of MΦ activation through control of substrate metabolism. Absence of FATP1 exacerbated pro-inflammatory activation in vitro and increased local and systemic components of the metabolic syndrome in HFD-fed Fatp1B−/− mice. In contrast, gain of FATP1 activity in MΦs suggested that Fatp1-mediated activation of fatty acids, substrate switch to glucose, oxidative stress, and lipid mediator synthesis are potential mechanisms. We demonstrate for the first time that FATP1 provides a unique mechanism by which the inflammatory tone of adipose and systemic metabolism may be regulated.

  3. Metabolic fate of poly-(lactic-co-glycolic acid-based curcumin nanoparticles following oral administration

    Directory of Open Access Journals (Sweden)

    Harigae T

    2016-06-01

    Full Text Available Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: Curcumin (CUR, the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid-based CUR nanoparticles (CUR-NP have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG, the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.Methods: Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.Results: Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with

  4. RESEARCH ON STRAIGHTENING TECHNOLOGY CAM SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Automatic straightening process is a nonlinear process, and affected by many factors.The straightening technology CAM system has been designed and built up to straighten shafts, which mainly consists of the straightening technology's database and the model of stroke-controlled precise straightening calculation model.The operational test of the CAM system has been passed.

  5. Onzichtbare beugels dankzij CAD-CAM

    NARCIS (Netherlands)

    F.R. de Winter

    2011-01-01

    De introductie van de cad-cam-techniek in de tandheelkunde heeft in de orthodontie geleid tot het orthodontisch verplaatsen van gebitselementen met een serie opeenvolgende dieptrekplaten, ontworpen en gefabriceerd met behulp van cad-cam. Daarbij is iedere plaat een kleine stap in de richting van de

  6. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Science.gov (United States)

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  7. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Science.gov (United States)

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  8. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Directory of Open Access Journals (Sweden)

    Hitomi Maruta

    Full Text Available Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4 genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A, which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  9. Urea and short-chain fatty acids metabolism in Holstein cows fed a low-nitrogen grass-based diet

    DEFF Research Database (Denmark)

    Røjen, B A; Lund, P; Kristensen, N B

    2008-01-01

    Three ruminally cannulated and multicatheterised lactating dairy cows were used to investigate the effect of different supplement strategies to fresh clover grass on urea and short-chain fatty acid (SCFA) metabolism in a zero-grazing experiment with 24-h blood and ruminal samplings.......Three ruminally cannulated and multicatheterised lactating dairy cows were used to investigate the effect of different supplement strategies to fresh clover grass on urea and short-chain fatty acid (SCFA) metabolism in a zero-grazing experiment with 24-h blood and ruminal samplings....

  10. A Branch Point of Streptomyces Sulfur Amino Acid Metabolism Controls the Production of Albomycin.

    Science.gov (United States)

    Kulkarni, Aditya; Zeng, Yu; Zhou, Wei; Van Lanen, Steven; Zhang, Weiwen; Chen, Shawn

    2016-01-01

    Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the gene cluster (abm) in the genome-sequenced S. griseus strain and proposed that the sulfur atom of ABM is derived from either cysteine (Cys) or homocysteine (Hcy). The gene product, AbmD, appears to be an important link between primary and secondary sulfur metabolic pathways. Here, we show that propargylglycine or iron supplementation in growth media increased ABM production by significantly changing the relative concentrations of intracellular Cys and Hcy. An SAA metabolic network of S. griseus was constructed. Pathways toward increasing Hcy were shown to positively impact ABM production. The abmD gene and five genes that increased the Hcy/Cys ratio were assembled downstream of hrdBp promoter sequences and integrated into the chromosome for overexpression. The ABM titer of one engineered strain, SCAK3, in a chemically defined medium was consistently improved to levels ∼400% of the wild type. Finally, we analyzed the production and growth of SCAK3 in shake flasks for further process development. PMID:26519385

  11. Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.

    Science.gov (United States)

    Bénit, Paule; Letouzé, Eric; Rak, Malgorzata; Aubry, Laetitia; Burnichon, Nelly; Favier, Judith; Gimenez-Roqueplo, Anne-Paule; Rustin, Pierre

    2014-08-01

    Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonetheless, the most striking observations have been made in the recent period while investigating human diseases, especially a set of specific cancers, revealing the crucial role of Krebs cycle intermediates as factors affecting genes methylation and thus cell remodeling. We review here the recent advances and persisting incognita about the role of Krebs cycle acids in diverse aspects of cellular life and human pathology.

  12. Fungal Community Associated with Dactylopius (Hemiptera: Coccoidea: Dactylopiidae) and Its Role in Uric Acid Metabolism

    Science.gov (United States)

    Vera-Ponce de León, Arturo; Sanchez-Flores, Alejandro; Rosenblueth, Mónica; Martínez-Romero, Esperanza

    2016-01-01

    We studied fungal species associated with the carmine cochineal Dactylopius coccus and other non-domesticated Dactylopius species using culture-dependent and -independent methods. Thirty seven fungi were isolated in various culture media from insect males and females from different developmental stages and Dactylopius species. 26S rRNA genes and ITS sequences, from cultured fungal isolates revealed different species of Cryptococcus, Rhodotorula, Debaryomyces, Trametes, and Penicillium, which are genera newly associated with Dactylopius. Uric acid (UA) and uricase activity were detected in tissues extracts from different insect developmental stages. However, accumulation of high UA levels and low uricase activities were found only after antifungal treatments, suggesting an important role of fungal species in its metabolism. Additionally, uricolytic fungal isolates were identified and characterized that presumably are involved in nitrogen recycling metabolism. After metagenomic analyses from D. coccus gut and hemolymph DNA and from two published data sets, we confirmed the presence of fungal genes involved in UA catabolism, suggesting that fungi help in the nitrogen recycling process in Dactylopius by uricolysis. All these results show the importance of fungal communities in scale insects such as Dactylopius. PMID:27446001

  13. [Ten-years records of organic arsenic (diphenylarsinic acid) poisoning: epidemiology, clinical feature, metabolism, and toxicity].

    Science.gov (United States)

    Ishi, Kazuhiro; Tamaoka, Akira

    2015-01-01

    We report here the symptoms of diphenylarsinic acid (DPAA) poisoning recorded over 10 years since the DPAA contamination of the potable well water was first detected in the Kamisu City, Ibaraki Prefecture, in 2003. The poisoning symptoms associated with the cerebellum and brainstem included nystagmus, tremors, myoclonus, and cerebellar ataxia as well as the symptoms associated with the temporal and occipital lobes such as memory impairment, sleep disorder, and visual disturbance. Some of the affected children exhibited mental retardation. Moreover, reduced blood flow and reduced glucose metabolism in the cerebella, brainstem, and temporal and occipital lobes persisted for several years among the DPAA-exposed persons. Based on the animal studies for DPAA intoxication, the target organs for the DPAA toxicity were determined to be the central nervous system (CNS), liver, and biliary system. In particular, DPAA tends to persist in the brain for a long time, resulting in long-term impacts on the brain. The cerebral blood flow and brain glucose metabolism, which can be measured by positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, are useful objective clinical markers to determine the effect of DPAA on CNS. We believe that continuous monitoring of the DPAA-exposed people may promote the effect of carcinogen and accelerate brain aging.

  14. From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria.

    Science.gov (United States)

    Gaspar, Paula; Carvalho, Ana L; Vinga, Susana; Santos, Helena; Neves, Ana Rute

    2013-11-01

    The lactic acid bacteria (LAB) are a functionally related group of low-GC Gram-positive bacteria known essentially for their roles in bioprocessing of foods and animal feeds. Due to extensive industrial use and enormous economical value, LAB have been intensively studied and a large body of comprehensive data on their metabolism and genetics was generated throughout the years. This knowledge has been instrumental in the implementation of successful applications in the food industry, such as the selection of robust starter cultures with desired phenotypic traits. The advent of genomics, functional genomics and high-throughput experimentation combined with powerful computational tools currently allows for a systems level understanding of these food industry workhorses. The technological developments in the last decade have provided the foundation for the use of LAB in applications beyond the classic food fermentations. Here we discuss recent metabolic engineering strategies to improve particular cellular traits of LAB and to design LAB cell factories for the bioproduction of added value chemicals.

  15. Algae in fish feed: performances and fatty acid metabolism in juvenile Atlantic Salmon.

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

    Full Text Available Algae are at the base of the aquatic food chain, producing the food resources that fish are adapted to consume. Previous studies have proven that the inclusion of small amounts (<10% of the diet of algae in fish feed (aquafeed resulted in positive effects in growth performance and feed utilisation efficiency. Marine algae have also been shown to possess functional activities, helping in the mediation of lipid metabolism, and therefore are increasingly studied in human and animal nutrition. The aim of this study was to assess the potentials of two commercially available algae derived products (dry algae meal, Verdemin (derived from Ulva ohnoi and Rosamin (derived from diatom Entomoneis spp. for their possible inclusion into diet of Atlantic Salmon (Salmo salar. Fish performances, feed efficiency, lipid metabolism and final product quality were assessed to investigated the potential of the two algae products (in isolation at two inclusion levels, 2.5% and 5%, or in combination, in experimental diets specifically formulated with low fish meal and fish oil content. The results indicate that inclusion of algae product Verdemin and Rosamin at level of 2.5 and 5.0% did not cause any major positive, nor negative, effect in Atlantic Salmon growth and feed efficiency. An increase in the omega-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA content in whole body of fish fed 5% Rosamin was observed.

  16. Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; HAN Xue-yao; JI Li-nong

    2010-01-01

    Background Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.Methods This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.Results Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.Conclusion This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.

  17. CitI, a Transcription Factor Involved in Regulation of Citrate Metabolism in Lactic Acid Bacteria†

    Science.gov (United States)

    Martin, Mauricio G.; Magni, Christian; de Mendoza, Diego; López, Paloma

    2005-01-01

    A large variety of lactic acid bacteria (LAB) can utilize citrate under fermentative conditions. Although much information concerning the metabolic pathways leading to citrate utilization by LAB has been gathered, the mechanisms regulating these pathways are obscure. In Weissella paramesenteroides (formerly called Leuconostoc paramesenteroides), transcription of the citMDEFCGRP citrate operon and the upstream divergent gene citI is induced by the presence of citrate in the medium. Although genetic experiments have suggested that CitI is a transcriptional activator whose activity can be modulated in response to citrate availability, specific details of the interaction between CitI and DNA remained unknown. In this study, we show that CitI recognizes two A+T-rich operator sites located between citI and citM and that the DNA-binding affinity of CitI is increased by citrate. Subsequently, this citrate signal propagation leads to the activation of the cit operon through an enhanced recruitment of RNA polymerase to its promoters. Our results indicate that the control of CitI by the cellular pools of citrate provides a mechanism for sensing the availability of citrate and adjusting the expression of the cit operon accordingly. In addition, this is the first reported example of a transcription factor directly functioning as a citrate-activated switch allowing the cell to optimize the generation of metabolic energy. PMID:16030208

  18. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease. PMID:27506797

  19. Fungal Community Associated with Dactylopius (Hemiptera: Coccoidea: Dactylopiidae) and Its Role in Uric Acid Metabolism.

    Science.gov (United States)

    Vera-Ponce de León, Arturo; Sanchez-Flores, Alejandro; Rosenblueth, Mónica; Martínez-Romero, Esperanza

    2016-01-01

    We studied fungal species associated with the carmine cochineal Dactylopius coccus and other non-domesticated Dactylopius species using culture-dependent and -independent methods. Thirty seven fungi were isolated in various culture media from insect males and females from different developmental stages and Dactylopius species. 26S rRNA genes and ITS sequences, from cultured fungal isolates revealed different species of Cryptococcus, Rhodotorula, Debaryomyces, Trametes, and Penicillium, which are genera newly associated with Dactylopius. Uric acid (UA) and uricase activity were detected in tissues extracts from different insect developmental stages. However, accumulation of high UA levels and low uricase activities were found only after antifungal treatments, suggesting an important role of fungal species in its metabolism. Additionally, uricolytic fungal isolates were identified and characterized that presumably are involved in nitrogen recycling metabolism. After metagenomic analyses from D. coccus gut and hemolymph DNA and from two published data sets, we confirmed the presence of fungal genes involved in UA catabolism, suggesting that fungi help in the nitrogen recycling process in Dactylopius by uricolysis. All these results show the importance of fungal communities in scale insects such as Dactylopius.

  20. Metabolism of D-lactate and structurally related organic acids in Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    During the initial minutes of anaerobiosis, 14C-labeled D-lactate, derived from the photosynthetic sugar phosphate pool, accumulated in the unicellular green alga, Chlamydomonas reinhardtii. The production of the D-isomer of lactate by algae is in contrast to plant and mammalian cells in which L-lactate is formed. After initial lactate formation, Chlamydomonas exhibits a mixed-acid type fermentation, thereby avoiding lactate accumulation and enabling the cells to tolerate extended periods of anaerobiosis. A pyruvate reductase which catalyzes the formation of D-lactate in Chlamydomonas was partially purified and characterized. Lactate produced anaerobically was metabolized only when Chlamydomonas cells were returned to aerobic conditions, and reoxidation of the D-lactate was apparently catalyzed by a mitochondrial membrane-bound dehydrogenase, rather than by the soluble pyruvate reductase. Mutants of Chlamydomonas, deficient in mitochondrial respiration, were used to demonstrate that lactate metabolism was linked to the mitochondrial electron transport chain. In addition, the oxidation of glycolate, a structural analog of lactate, was also linked to mitochondrial electron transport in vivo

  1. Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

    Science.gov (United States)

    Chaudhary, Kapil; Shinde, Rahul; Liu, Haiyun; Gnana-Prakasam, Jaya P; Veeranan-Karmegam, Rajalakshmi; Huang, Lei; Ravishankar, Buvana; Bradley, Jillian; Kvirkvelia, Nino; McMenamin, Malgorzata; Xiao, Wei; Kleven, Daniel; Mellor, Andrew L; Madaio, Michael P; McGaha, Tracy L

    2015-06-15

    Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN-γ-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2α kinase general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression. Thus, these findings support the hypothesis that the IDO-GCN2 pathway in glomerular stromal cells is a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy.

  2. Fungal Community Associated with Dactylopius (Hemiptera: Coccoidea: Dactylopiidae) and Its Role in Uric Acid Metabolism.

    Science.gov (United States)

    Vera-Ponce de León, Arturo; Sanchez-Flores, Alejandro; Rosenblueth, Mónica; Martínez-Romero, Esperanza

    2016-01-01

    We studied fungal species associated with the carmine cochineal Dactylopius coccus and other non-domesticated Dactylopius species using culture-dependent and -independent methods. Thirty seven fungi were isolated in various culture media from insect males and females from different developmental stages and Dactylopius species. 26S rRNA genes and ITS sequences, from cultured fungal isolates revealed different species of Cryptococcus, Rhodotorula, Debaryomyces, Trametes, and Penicillium, which are genera newly associated with Dactylopius. Uric acid (UA) and uricase activity were detected in tissues extracts from different insect developmental stages. However, accumulation of high UA levels and low uricase activities were found only after antifungal treatments, suggesting an important role of fungal species in its metabolism. Additionally, uricolytic fungal isolates were identified and characterized that presumably are involved in nitrogen recycling metabolism. After metagenomic analyses from D. coccus gut and hemolymph DNA and from two published data sets, we confirmed the presence of fungal genes involved in UA catabolism, suggesting that fungi help in the nitrogen recycling process in Dactylopius by uricolysis. All these results show the importance of fungal communities in scale insects such as Dactylopius. PMID:27446001

  3. Effects of glucose and ascorbic acid on absorption and first pass metabolism of isoniazid in rats.

    Science.gov (United States)

    Matsuki, Y; Katakuse, Y; Matsuura, H; Kiwada, H; Goromaru, T

    1991-02-01

    We examined the effect of glucose (Glu) and ascorbic acid (AA) on absorption and metabolism of isoniazid (INAH). After p.o. administration of INAH with or without Glu or AA, plasma concentration and urinary excretion of INAH and its metabolites, acetyl INAH (AcINAH), acetyl hydrazine (AcHy) and hydrazine (Hy), were determined by means of gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standard. The combined administration of INAH with Glu or AA led to a significant decrease in the excretion of INAH and Hy, and a significant increase in the excretion of AcINAH and AcHy. The absorption amount of INAH was reduced to about one-half by the addition of Glu and the absorption rate of INAH markedly decreased in the case of co-administration of AA. Comparing the oral case with the results of i.v. administration, Glu and AA only affect the absorption process containing the first pass metabolism of INAH.

  4. Organic acid metabolism and root excretion of malate in wheat cultivars under aluminium stress.

    Science.gov (United States)

    de Andrade, Leide Rovênia Miranda; Ikeda, Motoki; do Amaral, Lourdes Isabel Velho; Ishizuka, Junji

    2011-01-01

    The effects of aluminium (Al) on the metabolism of organic acids synthesised via nonphotosynthetic carbon fixation in the roots and on malate exudation were investigated in Al-tolerant Shirosanjyaku (SH) and Al-sensitive Chikushikomugi (CK) wheat cultivars labelled with bicarbonate-(14)C. Aluminum triggered the excretion of (14)C into the solution, especially in the SH that excreted 2.5 times more (14)C than the CK. The loss of radioactivity (about 10%) into the solution represented a small drain in the (14)C reserve found in the roots. In the organic acid fraction within the roots, malate contained the greatest amount of (14)C, and this amount decreased rapidly with time in both cultivars. The disappearance of radioactivity in the malate resulted from metabolism and translocation rather than to root efflux. Aluminium decreased the malate concentrations in roots of both cultivars. The Al-sensitive cultivar had higher concentrations of malate regardless of the presence of Al. It was therefore assumed that the decrease of malate concentration in roots under Al stress did not result from the decline in malate synthesis but due to an increase in malate decomposition. This response was interpreted as the result of the Al-induced stress and not as the cause of a differential Al-tolerance between the wheat cultivars. An important component of the differential Al tolerance between SH and CK is the greater ability of the Al-tolerant cultivar to excrete malate from the roots, which is independent of its internal concentration in the roots.

  5. Comparative Transcriptomics Reveals Jasmonic Acid-Associated Metabolism Related to Cotton Fiber Initiation.

    Directory of Open Access Journals (Sweden)

    Liman Wang

    Full Text Available Analysis of mutants and gene expression patterns provides a powerful approach for investigating genes involved in key stages of plant fiber development. In this study, lintless-fuzzless XinWX and linted-fuzzless XinFLM with a single genetic locus difference for lint were used to identify differentially expressed genes. Scanning electron microscopy showed fiber initiation in XinFLM at 0 days post anthesis (DPA. Fiber transcriptional profiling of the lines at three initiation developmental stages (-1, 0, 1 DPA was performed using an oligonucleotide microarray. Loop comparisons of the differentially expressed genes within and between the lines was carried out, and functional classification and enrichment analysis showed that gene expression patterns during fiber initiation were heavily associated with hormone metabolism, transcription factor regulation, lipid transport, and asparagine biosynthetic processes, as previously reported. Further, four members of the allene-oxide cyclase (AOC family that function in jasmonate biosynthesis were parallel up-regulation in fiber initiation, especially at -1 DPA, compared to other tissues and organs in linted-fuzzed TM-1. Real time-quantitative PCR (RT-qPCR analysis in different fiber mutant lines revealed that AOCs were up-regulated higher at -1 DPA in lintless-fuzzless than that in linted-fuzzless and linted-fuzzed materials, and transcription of the AOCs was increased under jasmonic acid (JA treatment. Expression analysis of JA biosynthesis-associated genes between XinWX and XinFLM showed that they were up-regulated during fiber initiation in the fuzzless-lintless mutant. Taken together, jasmonic acid-associated metabolism was related to cotton fiber initiation. Parallel up-regulation of AOCs expression may be important for normal fiber initiation development, while overproduction of AOCs might disrupt normal fiber development.

  6. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  7. Eugenol: a dual inhibitor of platelet-activating factor and arachidonic acid metabolism.

    Science.gov (United States)

    Saeed, S A; Simjee, R U; Shamim, G; Gilani, A H

    1995-07-01

    Eugenol is an active principal and responsible for several pharmacological activities of clove oil. We studied the effects of eugenol on human platelet aggregation, arachidonic acid (AA) and platelet-activating factor (PAF) metabolism and in vivo effects on AA and PAF-induced shock in rabbits. Eugenol strongly inhibited PAF-induced platelet aggregation with lesser effect against AA and collegen. The IC(50) values were against AA: 31 ± 0.5; collagen: 64 ± 0.7 and PAF 7 ± 0.2 μM (n=9) respectively. In addition, eugenol stimulated PAF-acetylhydrolase activity suggesting that inhibition of PAF could be due to its inactivation to lyso-PAF. Pretreatment of rabbits with eugenol (50-100 mg/kg) prevented the lethal effects of intravenous PAF (11 μgg/kg) or AA (2 mg/kg) in a dose-dependent fashion. The protective effects of eugenol in the rabbits, however, were more pronounced against PAF-induced mortality (100% protection). In addition, eugenol also inhibited AA metabolism via cyclooxygenase and lipoxygenase pathways in human platelets. Both the production of thromboxane-A(2) and 12-hydroxy-eicosatetraenoic acid was inhibited by eugenol in a concentration-related manner (30-120 μM). In vivo, eugenol (50-100 mg/kg; i.p.) inhibited carrageenan-induced rat paw oedema (P < 0.001). In this test, eugenol was 5 times more potent than aspirin. These results provide evidence that eugenol acts as a dual antagonist of AA and PAF. PMID:23196096

  8. Influence of C18 long chain fatty acids on hydrogen metabolism.

    Science.gov (United States)

    Templer, Jennifer; Lalman, Jerald A; Jing, Nin; Ndegwa, Pius M

    2006-01-01

    During anaerobic treatment, several microorganisms mediate a series of reactions to convert reduced compounds (electron donors) into methane. Inhibitors such as long chain fatty acids (LCFAs) can affect several anaerobic microbial populations and decrease the treatment efficiency. The effects of three C18 LCFAs on hydrogenotrophic methanogens in a flocculated mixed anaerobic culture were assessed in this study. The reaction half-life and the hydrogen versus time profiles were used to characterize the inhibition process. The half-life values and profiles were similar for controls and cultures exposed to LCFAs for 1 h. The hydrogen inhibition was a function of the exposure time and the LCFA concentration except for cultures exposed to stearic acid (SA). A statistical analysis of the reaction half-life for cultures incubated with 1,500 and 2,000 mg L(-1) LCFAs for 48 h, revealed the following inhibition trend: linoleic acid (LA) > oleic acid (OA) > SA. After 48 h of exposure, no clear inhibition trend was observed for cultures inoculated with LCFA mixtures; however, at levels of 1,500 and 2,000 mg L(-1), the reaction half-life values were less than that observed for cultures fed with only LA. Based on the reaction half-life data, all of the LCFAs except SA at threshold levels of approximately 1,500 mg L(-1) inhibited hydrogen metabolism. The greatest inhibition and, hence, the largest amount of accumulated hydrogen was observed in cultures fed with 2,000 mg L(-1) LA and incubated for 48 h.

  9. Plasma fatty acids profile and estimated elongase and desaturases activities in Tunisian patients with the metabolic syndrome.

    Science.gov (United States)

    Sethom, M M; Fares, S; Feki, M; Hadj-Taieb, S; Elasmi, M; Omar, S; Sanhaji, H; Jemaa, R; Kaabachi, N

    2011-01-01

    This study aimed to determine plasma fatty acids pattern and to estimate desaturases activities in Tunisian subjects with metabolic syndrome (MetS). A total of 1975 adults were randomly selected from the Great Tunis region (Tunisia). MetS was defined according to the International Diabetes Federation criteria. Saturated and monounsaturated fatty acids levels and delta 9 desaturase activity were increased, but polyunsaturated fatty acids (PUFA) levels and delta 5 desaturase activity were decreased in patients with MetS. Using multivariate analysis, MetS was found inversely associated with PUFA; compared to first quartile, multi-adjusted odd ratios (95% confidence interval) of MetS were 0.80 (0.54-1.17), 0.47 (0.27-0.81) and 0.32 (0.15-0.68) for second, third and fourth quartiles of PUFA, respectively. Altered fatty acids pattern in MetS is likely related to both dietary and metabolic changes. PMID:21782403

  10. Benzyl esters of C2-C20 fatty acids and metabolically relevant carboxylic acids. Preparation and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Schatowitz, B; Gercken, G

    1987-11-13

    Short-, medium- and long-chain fatty acids, and other types of metabolically relevant carboxylic acids like hydroxy-, keto-, aromatic and dicarboxylic acids, were analyzed by capillary gas chromatography. For separation, benzyl ester derivatives were used, prepared by reaction of the potassium carboxylates with benzyl bromide in acetonitrile catalyzed by a crown ether. The reaction conditions for quantitative benzylation were studied. Keto groups of ketocarboxylic acids were stabilized prior to benzylation by formation of O-methyl oximes using methoxyamine hydrochloride in aqueous-ethanolic solution. The separation of more than 45 carboxylic acids was achieved on a CP-Sil 5 CB fused-silica capillary column in less than 70 min. The electron impact mass spectra of ketocarboxylic acid O-methyl oxime benzyl esters PMID:3693495

  11. Bile acid metabolism in hereditary forms of hypertriglyceridemia: evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia.

    OpenAIRE

    Angelin, B; Hershon, K S; Brunzell, J D

    1987-01-01

    This study was undertaken to characterize bile acid metabolism in hereditary forms of hypertriglyceridemia. Ten hypertriglyceridemic patients (type IV phenotype) with familial combined hyperlipidemia and 7 patients with monogenic familial hypertriglyceridemia (FHTG) were compared with 18 healthy controls; all subjects were males. Pool size, synthesis rate, and fractional catabolic rate of cholic and chenodeoxycholic acids were determined with an isotope dilution technique. Patients with FHTG ...

  12. Current Perspective on the Location and Function of Gamma- Aminobutyric Acid (GABA) and its Metabolic Partners in the Kidney.

    OpenAIRE

    Dunn, Kadeshia; Peppiatt-Wildman, Claire M.; Kelley, Stephen P; Wildman, Scott S.P.

    2014-01-01

    Abstract: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter located in the mammalian central nervous system, which binds to GABAA and GABAB receptors to mediate its neurological effects. In addition to its role in the CNS, an increasing number of publications have suggested that GABA might also play a role in the regulation of renal function. All three enzymes associated with GABA metabolism; glutamic acid decarboxylase, GABA α-oxoglutarate transaminase (GABA-T) and succinic se...

  13. Increased expression of fatty-acid and calcium metabolism genes in failing human heart.

    Directory of Open Access Journals (Sweden)

    Vanessa García-Rúa

    Full Text Available BACKGROUND: Heart failure (HF involves alterations in metabolism, but little is known about cardiomyopathy-(CM-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA uptake and oxidation or in calcium-(Ca(2+-handling in the human heart. METHODS: RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36 without diabetes mellitus of ischaemic (ICM, n = 16 or dilated (DCM, n = 20 cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6. RESULTS: Significant increases in mRNA of genes regulating FA uptake (CD36 and intracellular transport (Heart-FA-Binding Protein (HFABP were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA, PPAR-gamma coactivator-1-alpha (PGC1A and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+-handling genes (Two-Pore-Channel 1 (TPCN1, Two-Pore-Channel 2 (TPCN2, and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1 increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL: three were common to and three distinct from ICM. CONCLUSION: DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2

  14. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

    Science.gov (United States)

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve

  15. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  16. Agave as a model CAM crop system for a warming and drying world.

    Science.gov (United States)

    Stewart, J Ryan

    2015-01-01

    As climate change leads to drier and warmer conditions in semi-arid regions, growing resource-intensive C3 and C4 crops will become more challenging. Such crops will be subjected to increased frequency and intensity of drought and heat stress. However, agaves, even more than pineapple (Ananas comosus) and prickly pear (Opuntia ficus-indica and related species), typify highly productive plants that will respond favorably to global warming, both in natural and cultivated settings. With nearly 200 species spread throughout the U.S., Mexico, and Central America, agaves have evolved traits, including crassulacean acid metabolism (CAM), that allow them to survive extreme heat and drought. Agaves have been used as sources of food, beverage, and fiber by societies for hundreds of years. The varied uses of Agave, combined with its unique adaptations to environmental stress, warrant its consideration as a model CAM crop. Besides the damaging cycles of surplus and shortage that have long beset the tequila industry, the relatively long maturation cycle of Agave, its monocarpic flowering habit, and unique morphology comprise the biggest barriers to its widespread use as a crop suitable for mechanized production. Despite these challenges, agaves exhibit potential as crops since they can be grown on marginal lands, but with more resource input than is widely assumed. If these constraints can be reconciled, Agave shows considerable promise as an alternative source for food, alternative sweeteners, and even bioenergy. And despite the many unknowns regarding agaves, they provide a means to resolve disparities in resource availability and needs between natural and human systems in semi-arid regions. PMID:26442005

  17. Agave as a model CAM crop system for a warming and drying world

    Science.gov (United States)

    Stewart, J. Ryan

    2015-01-01

    As climate change leads to drier and warmer conditions in semi-arid regions, growing resource-intensive C3 and C4 crops will become more challenging. Such crops will be subjected to increased frequency and intensity of drought and heat stress. However, agaves, even more than pineapple (Ananas comosus) and prickly pear (Opuntia ficus-indica and related species), typify highly productive plants that will respond favorably to global warming, both in natural and cultivated settings. With nearly 200 species spread throughout the U.S., Mexico, and Central America, agaves have evolved traits, including crassulacean acid metabolism (CAM), that allow them to survive extreme heat and drought. Agaves have been used as sources of food, beverage, and fiber by societies for hundreds of years. The varied uses of Agave, combined with its unique adaptations to environmental stress, warrant its consideration as a model CAM crop. Besides the damaging cycles of surplus and shortage that have long beset the tequila industry, the relatively long maturation cycle of Agave, its monocarpic flowering habit, and unique morphology comprise the biggest barriers to its widespread use as a crop suitable for mechanized production. Despite these challenges, agaves exhibit potential as crops since they can be grown on marginal lands, but with more resource input than is widely assumed. If these constraints can be reconciled, Agave shows considerable promise as an alternative source for food, alternative sweeteners, and even bioenergy. And despite the many unknowns regarding agaves, they provide a means to resolve disparities in resource availability and needs between natural and human systems in semi-arid regions. PMID:26442005

  18. Agave as a model CAM crop system for a warming and drying world

    Directory of Open Access Journals (Sweden)

    J. Ryan eStewart

    2015-09-01

    Full Text Available As climate change leads to drier and warmer conditions in semi-arid regions, growing resource-intensive C3 and C4 crops will become more challenging. Such crops will be subjected to increased frequency and intensity of drought and heat stress. However, agaves, even more than pineapple (Ananas comosus and prickly pear (Opuntia ficus-indica and related species, typify highly productive plants that will respond favorably to global warming, both in natural and cultivated settings. With nearly 200 species spread throughout the U.S., Mexico, and Central America, agaves have evolved traits, including crassulacean acid metabolism (CAM, that allow them to survive extreme heat and drought. Agaves have been used as sources of food, beverage, and fiber by societies for hundreds of years. The varied uses of Agave, combined with its unique adaptations to environmental stress, warrant its consideration as a model CAM crop. Besides the damaging cycles of surplus and shortage that have long beset the tequila industry, the relatively long maturation cycle of Agave, its monocarpic flowering habit, and unique morphology comprise the biggest barriers to its widespread use as a crop suitable for mechanized production. Despite these challenges, agaves exhibit potential as crops since they can be grown on marginal lands, but with more resource input than is widely assumed. If these constraints can be reconciled, Agave shows considerable promise as an alternative source for food, alternative sweeteners, and even bioenergy. And despite the many unknowns regarding agaves, they provide a means to resolve disparities between natural and human systems in semi-arid regions.

  19. Inflammatory markers in patients with metabolic syndrome after the intake of fatty acids n-3 and conjugated linoleic acid (CLA

    Directory of Open Access Journals (Sweden)

    Campos Mondragón, M.G; Oliart Ros, R. M. ; Angulo Guerrero, J. O.

    2013-03-01

    Full Text Available ABSTRACTIntroduction: The metabolic syndrome (MS increa -ses the odds of dying for cardiovascular disease, theworld’s leading cause of death. It has been shown thatpolyunsaturated fatty acids have a protective role in cardiovascular disease and its comorbidities.Objective: To assess the effect of three kinds ofpolyunsaturated fatty acids on the chronic inflammation in MS.Methods: The study group was 45 adults with MSdiagnose according to IDF criteria. Each group of treatment was assigned cuasi-randomly to 15 subjects during six weeks: a 1.8 g/d n-3 (1.08 g eicosapentoaenoicacid EPA + 0.72 g docosahexaenoic acid DHA, b 2.0g/d conjugated linoleic acid (CLA, 50:50, cis9:trans11,trans10:cis12, c 40 g/d walnut Juglans regia. The results at the beginning and the end of the essay werecompared in each group, using the t-Student test and p <0.01 as statistical signification value.Results:In the patients supplemented with n-3 fattyacids, significantly decreased the level of IL-6 (from9.81 ±1.28 to 8.47 ±0.81 pg/ml, p=0.002, leptin(from 25.94 ±5.06 ng/ml to 20.53 ±3.96 ng/ml,p=0.003 and homocysteine (from 18.80 ±1.95 to16.72 ±1.99 µmol/l, p=0.007, in erythrocytes decreased the percentage α-linolenic content (from 1.90±0.77 to 1.26 ±0.17 %, p=0.004 and the n6/n3 rate(from 4.48 ±1.06 to 3.11 a ±0.60, p=0.000, while increased the percentage of EPA (from 1.13 ±0.45 to1.58 ±0.42 %, p=0.009 and DHA (from 2.61 ±0.36 to4.64 ±0.91 %, p=0.000. In the group that consumedwalnut declined the levels of TNF-α (from 8.75 ±2.06pg/ml to 6.68 ±0.97 pg/ml, p=0.002 and IL-6 (from10.61 ±1.45 to 8.72 ±0.79 pg/ml, p=0.000, in erythrocytes increased the α-linolenic content (from 1.86±0.65 to 2.62 ±0.72 %, p=0.005. In the group thatconsumed CLA decreased the level of homocysteine(from 18.01 ±2.65 to 15.34 ±2.26 µmol/l, p=0.006.Conclusions: The groups that consumed n-3 fattyacids in supplements (EPA/DHA and in walnut, becameevident the modification in

  20. Improved Acetic Acid Resistance in Saccharomyces cerevisiae by Overexpression of the WHI2 Gene Identified through Inverse Metabolic Engineering.

    Science.gov (United States)

    Chen, Yingying; Stabryla, Lisa; Wei, Na

    2016-01-29

    Development of acetic acid-resistant Saccharomyces cerevisiae is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge due to limited information on effective genetic perturbation targets for improving acetic acid resistance in the yeast. This study employed a genomic-library-based inverse metabolic engineering approach to successfully identify a novel gene target, WHI2 (encoding a cytoplasmatic globular scaffold protein), which elicited improved acetic acid resistance in S. cerevisiae. Overexpression of WHI2 significantly improved glucose and/or xylose fermentation under acetic acid stress in engineered yeast. The WHI2-overexpressing strain had 5-times-higher specific ethanol productivity than the control in glucose fermentation with acetic acid. Analysis of the expression of WHI2 gene products (including protein and transcript) determined that acetic acid induced endogenous expression of Whi2 in S. cerevisiae. Meanwhile, the whi2Δ mutant strain had substantially higher susceptibility to acetic acid than the wild type, suggesting the important role of Whi2 in the acetic acid response in S. cerevisiae. Additionally, overexpression of WHI2 and of a cognate phosphatase gene, PSR1, had a synergistic effect in improving acetic acid resistance, suggesting that Whi2 might function in combination with Psr1 to elicit the acetic acid resistance mechanism. These results improve our understanding of the yeast response to acetic acid stress and provide a new strategy to breed acetic acid-resistant yeast strains for renewable biofuel production.

  1. Amino acid metabolism during total parenteral nutrition in healthy volunteers: evaluation of a new amino acid solution.

    Science.gov (United States)

    Berard, M P; Hankard, R; Cynober, L

    2001-10-01

    The aim of this study was to determine the metabolism and the tolerance of a new amino acid (AA) solution administered under conditions mimicking cyclical parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1) (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake was increased progressively for 90 min; thereafter, AA infusion was started and maintained at a constant rate for 10 h. Plasma and urine concentrations of all the AAs were measured before, during and after the PN. For each given AA, the relation between plasma variations at the steady-state and infusion rate, plasma clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during the PN period. The results are presented as means+/-sem. All plasma AA concentrations decreased during the starting period of non-protein energy intake. The plasma AA concentrations reached a steady-state within 3 h upon AA infusion, except for glycine and lysine (6 h). At the steady state, the plasma concentrations of the infused AAs were closely correlated to their infusion rate (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained during the PN, which indicates that the solution might stimulate the de novo synthesis of this AA. When the PN was stopped, plasma levels of the AAs decreased, most of them returning to their basal levels, or significantly below for lysine (Por= 99%, Reten >or=99% and for non-essential AAs: Cl or= 98% except glycine (95+/-1), aspartate (94+/-2) and histidine (94+/-1), Reten >or=97% except histidine (94+/-1), glycine (95+/-3). These results indicate that in healthy subjects, the amounts of AAs provided by the new solution were well balanced for an intravenous administration, and so were well utilized without excessive urinary excretion. The present study

  2. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

    Directory of Open Access Journals (Sweden)

    Sebastiano Collino

    Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

  3. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R.J.; Lok, A.; Ruhe, H.G.; Pouwer, F.; Schene, A.H.

    2014-01-01

    OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  4. Metabolism of clofibric acid in zebrafish embryos (Danio rerio) as determined by liquid chromatography-high resolution-mass spectrometry.

    Science.gov (United States)

    Brox, Stephan; Seiwert, Bettina; Haase, Nora; Küster, Eberhard; Reemtsma, Thorsten

    2016-01-01

    The zebrafish embryo (ZFE) is increasingly used in ecotoxicology research but detailed knowledge of its metabolic potential is still limited. This study focuses on the xenobiotic metabolism of ZFE at different life-stages using the pharmaceutical compound clofibric acid as study compound. Liquid chromatography with quadrupole-time-of-flight mass spectrometry (LC-QToF-MS) is used to detect and to identify the transformation products (TPs). In screening experiments, a total of 18 TPs was detected and structure proposals were elaborated for 17 TPs, formed by phase I and phase II metabolism. Biotransformation of clofibric acid by the ZFE involves conjugation with sulfate or glucuronic acid, and, reported here for the first time, with carnitine, taurine, and aminomethanesulfonic acid. Further yet unknown cyclization products were identified using non-target screening that may represent a new detoxification pathway. Sulfate containing TPs occurred already after 3h of exposure (7hpf), and from 48h of exposure (52hpf) onwards, all TPs were detected. The detection of these TPs indicates the activity of phase I and phase II enzymes already at early life-stages. Additionally, the excretion of one TP into the exposure medium was observed. The results of this study outline the high metabolic potential of the ZFE with respect to the transformation of xenobiotics. Similarities but also differences to other test systems were observed. Biotransformation of test chemicals in toxicity testing with ZFE may therefore need further consideration. PMID:26945519

  5. Association of adiponectin,free fatty acids,and insulin resistance with metabolic syndrome and its components in Uygur Xinjiang

    Institute of Scientific and Technical Information of China (English)

    闫贻忠

    2014-01-01

    Objective To investigate the association of adiponectin(APN),free fatty acids(FFA),and insulin resistance(IR)with metabolic syndrome(MS)and its components.Methods In the baseline survey,the subjects were divided into MS group and the control group based

  6. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore

  7. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

    NARCIS (Netherlands)

    Besten, G. den; Eunen, K. van; Groen, A.K.; Venema, K.; Reijngoud, D.J.; Bakker, B.M.

    2013-01-01

    Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass

  8. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R. J. T.; Lok, A.; Ruhe, H. G.; Pouwer, F.; Schene, A. H.

    2014-01-01

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  9. Metabolism of clofibric acid in zebrafish embryos (Danio rerio) as determined by liquid chromatography-high resolution-mass spectrometry.

    Science.gov (United States)

    Brox, Stephan; Seiwert, Bettina; Haase, Nora; Küster, Eberhard; Reemtsma, Thorsten

    2016-01-01

    The zebrafish embryo (ZFE) is increasingly used in ecotoxicology research but detailed knowledge of its metabolic potential is still limited. This study focuses on the xenobiotic metabolism of ZFE at different life-stages using the pharmaceutical compound clofibric acid as study compound. Liquid chromatography with quadrupole-time-of-flight mass spectrometry (LC-QToF-MS) is used to detect and to identify the transformation products (TPs). In screening experiments, a total of 18 TPs was detected and structure proposals were elaborated for 17 TPs, formed by phase I and phase II metabolism. Biotransformation of clofibric acid by the ZFE involves conjugation with sulfate or glucuronic acid, and, reported here for the first time, with carnitine, taurine, and aminomethanesulfonic acid. Further yet unknown cyclization products were identified using non-target screening that may represent a new detoxification pathway. Sulfate containing TPs occurred already after 3h of exposure (7hpf), and from 48h of exposure (52hpf) onwards, all TPs were detected. The detection of these TPs indicates the activity of phase I and phase II enzymes already at early life-stages. Additionally, the excretion of one TP into the exposure medium was observed. The results of this study outline the high metabolic potential of the ZFE with respect to the transformation of xenobiotics. Similarities but also differences to other test systems were observed. Biotransformation of test chemicals in toxicity testing with ZFE may therefore need further consideration.

  10. An autopsy case of death due to metabolic acidosis after citric acid ingestion.

    Science.gov (United States)

    Ikeda, Tomoya; Usui, Akihito; Matsumura, Takashi; Aramaki, Tomomi; Hosoya, Tadashi; Igari, Yui; Ohuchi, Tsukasa; Hayashizaki, Yoshie; Usui, Kiyotaka; Funayama, Masato

    2015-11-01

    A man in his 40s was found unconscious on a sofa in a communal residence for people with various disabilities. He appeared to have drunk 800 ml of undiluted citric acid from a commercial plastic bottle. The instructions on the label of the beverage specified that the beverage be diluted 20- to 30-fold before consumption. The patient was admitted to an emergency hospital with severe metabolic acidosis (pH, 6.70; HCO3(-), 3.6 mEq/L) and a low ionized calcium level (0.73 mmol/L). Although ionized calcium and catecholamines were continuously administered intravenously to correct the acidosis, the state of acidemia and low blood pressure did not improve, and he died 20 h later. Citric acid concentrations in the patient's serum drawn shortly after treatment in the hospital and from the heart at autopsy were 80.6 mg/ml and 39.8 mg/dl, respectively (normal range: 1.3-2.6 mg/dl). Autopsy revealed black discoloration of the mucosal surface of the esophagus. Microscopically, degenerated epithelium and neutrophilic infiltration in the muscle layer were observed. In daily life, drinking a large amount of concentrated citric acid beverage is rare as a cause of lethal poisoning. However, persons with mental disorders such as dementia may mistakenly drink detergent or concentrated fluids, as in our case. Family members or facility staff in the home or nursing facility must bear in mind that they should not leave such bottles in places where they are easily accessible to mentally handicapped persons.

  11. Anaerobic hydrocarbon and fatty acid metabolism by syntrophic bacteria and their impact on carbon steel corrosion

    Directory of Open Access Journals (Sweden)

    Christopher Neil Lyles

    2014-04-01

    Full Text Available The microbial metabolism of hydrocarbons is increasingly associated with the corrosion of carbon steel in sulfate-rich marine waters. However, how such transformations influence metal biocorrosion in the absence of an electron acceptor is not fully recognized. We grew a marine alkane-utilizing, sulfate-reducing bacterium, Desulfoglaeba alkanexedens, with either sulfate or Methanospirillum hungatei as electron acceptors, and tested the ability of the cultures to catalyze metal corrosion. Axenically, D. alkanexedens had a higher instantaneous corrosion rate and produced more pits in carbon steel coupons than when the same organism was grown in syntrophic co-culture with the methanogen. Since anaerobic hydrocarbon biodegradation pathways converge on fatty acid intermediates, the corrosive ability of a known fatty acid-oxidizing syntrophic bacterium, Syntrophus aciditrophicus was compared when grown in pure culture or in co-culture with a H2-utilizing sulfate-reducing bacterium (Desulfovibrio sp., strain G11 or a methanogen (M. hungatei. The instantaneous corrosion rates in the cultures were not substantially different, but the syntrophic, sulfate-reducing co-culture produced more pits in coupons than other combinations of microorganisms. Lactate-grown cultures of strain G11 had higher instantaneous corrosion rates and coupon pitting compared to the same organism cultured with hydrogen as an electron donor. Thus, if sulfate is available as an electron acceptor, the same microbial assemblages produce sulfide and low molecular weight organic acids that exacerbated biocorrosion. Despite these trends, a surprisingly high degree of variation was encountered with the corrosion assessments. Differences in biomass, initial substrate concentration, rates of microbial activity or the degree of end product formation did not account for the variations. We are forced to ascribe such differences to the metallurgical properties of the coupons.

  12. Anaerobic hydrocarbon and fatty acid metabolism by syntrophic bacteria and their impact on carbon steel corrosion.

    Science.gov (United States)

    Lyles, Christopher N; Le, Huynh M; Beasley, William Howard; McInerney, Michael J; Suflita, Joseph M

    2014-01-01

    The microbial metabolism of hydrocarbons is increasingly associated with the corrosion of carbon steel in sulfate-rich marine waters. However, how such transformations influence metal biocorrosion in the absence of an electron acceptor is not fully recognized. We grew a marine alkane-utilizing, sulfate-reducing bacterium, Desulfoglaeba alkanexedens, with either sulfate or Methanospirillum hungatei as electron acceptors, and tested the ability of the cultures to catalyze metal corrosion. Axenically, D. alkanexedens had a higher instantaneous corrosion rate and produced more pits in carbon steel coupons than when the same organism was grown in syntrophic co-culture with the methanogen. Since anaerobic hydrocarbon biodegradation pathways converge on fatty acid intermediates, the corrosive ability of a known fatty acid-oxidizing syntrophic bacterium, Syntrophus aciditrophicus was compared when grown in pure culture or in co-culture with a H2-utilizing sulfate-reducing bacterium (Desulfovibrio sp., strain G11) or a methanogen (M. hungatei). The instantaneous corrosion rates in the cultures were not substantially different, but the syntrophic, sulfate-reducing co-culture produced more pits in coupons than other combinations of microorganisms. Lactate-grown cultures of strain G11 had higher instantaneous corrosion rates and coupon pitting compared to the same organism cultured with hydrogen as an electron donor. Thus, if sulfate is available as an electron acceptor, the same microbial assemblages produce sulfide and low molecular weight organic acids that exacerbated biocorrosion. Despite these trends, a surprisingly high degree of variation was encountered with the corrosion assessments. Differences in biomass, initial substrate concentration, rates of microbial activity or the degree of end product formation did not account for the variations. We are forced to ascribe such differences to the metallurgical properties of the coupons.

  13. CAM Stochastic Volatility Model for Option Pricing

    Directory of Open Access Journals (Sweden)

    Wanwan Huang

    2016-01-01

    Full Text Available The coupled additive and multiplicative (CAM noises model is a stochastic volatility model for derivative pricing. Unlike the other stochastic volatility models in the literature, the CAM model uses two Brownian motions, one multiplicative and one additive, to model the volatility process. We provide empirical evidence that suggests a nontrivial relationship between the kurtosis and skewness of asset prices and that the CAM model is able to capture this relationship, whereas the traditional stochastic volatility models cannot. We introduce a control variate method and Monte Carlo estimators for some of the sensitivities (Greeks of the model. We also derive an approximation for the characteristic function of the model.

  14. Cad/cam-tekniikan kannattavuus hammastekniikassa

    OpenAIRE

    Kinnunen, Vilho

    2012-01-01

    Hammaslaboratorioissa tehdään cad/cam-tekniikalla kiinteän protetiikan töitä. Opinnäytetyössäni tarkastelen, kuinka kannattavaa on valmistaa jyrsintekniikalla kiinteän protetiikan valmisteita. Selvitän millainen cad/cam-tekniikkaa käyttävä yritys pitää olla, jotta se on kannattava. Opinnäytetyöni aineiston keruun tein haastattelemalla cad/cam tekniikkaa ja perinteistä tekniikkaa käyttävien hammaslaboratorioiden omistajia. Haastattelun toteutin teemahaastatteluna. Kehitin laajuuskäsitteen,...

  15. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    International Nuclear Information System (INIS)

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks

  16. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory, E-mail: Tory.Hagen@oregonstate.edu [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  17. Integrated bioinformatics to decipher the ascorbic acid metabolic network in tomato.

    Science.gov (United States)

    Ruggieri, Valentino; Bostan, Hamed; Barone, Amalia; Frusciante, Luigi; Chiusano, Maria Luisa

    2016-07-01

    Ascorbic acid is involved in a plethora of reactions in both plant and animal metabolism. It plays an essential role neutralizing free radicals and acting as enzyme co-factor in several reaction. Since humans are ascorbate auxotrophs, enhancing the nutritional quality of a widely consumed vegetable like tomato is a desirable goal. Although the main reactions of the ascorbate biosynthesis, recycling and translocation pathways have been characterized, the assignment of tomato genes to each enzymatic step of the entire network has never been reported to date. By integrating bioinformatics approaches, omics resources and transcriptome collections today available for tomato, this study provides an overview on the architecture of the ascorbate pathway. In particular, 237 tomato loci were associated with the different enzymatic steps of the network, establishing the first comprehensive reference collection of candidate genes based on the recently released tomato gene annotation. The co-expression analyses performed by using RNA-Seq data supported the functional investigation of main expression patterns for the candidate genes and highlighted a coordinated spatial-temporal regulation of genes of the different pathways across tissues and developmental stages. Taken together these results provide evidence of a complex interplaying mechanism and highlight the pivotal role of functional related genes. The definition of genes contributing to alternative pathways and their expression profiles corroborates previous hypothesis on mechanisms of accumulation of ascorbate in the later stages of fruit ripening. Results and evidences here provided may facilitate the development of novel strategies for biofortification of tomato fruit with Vitamin C and offer an example framework for similar studies concerning other metabolic pathways and species. PMID:27007138

  18. Highly selective production of succinic acid by metabolically engineered Mannheimia succiniciproducens and its efficient purification.

    Science.gov (United States)

    Choi, Sol; Song, Hyohak; Lim, Sung Won; Kim, Tae Yong; Ahn, Jung Ho; Lee, Jeong Wook; Lee, Moon-Hee; Lee, Sang Yup

    2016-10-01

    Succinic acid (SA) is one of the fermentative products of anaerobic metabolism, and an important industrial chemical that has been much studied for its bio-based production. The key to the economically viable bio-based SA production is to develop an SA producer capable of producing SA with high yield and productivity without byproducts. Mannheimia succiniciproducens is a capnophilic rumen bacterium capable of efficiently producing SA. In this study, in silico genome-scale metabolic simulations were performed to identify gene targets to be engineered, and the PALK strain (ΔldhA and Δpta-ackA) was constructed. Fed-batch culture of PALK on glucose and glycerol as carbon sources resulted in the production of 66.14 g/L of SA with the yield and overall productivity of 1.34 mol/mol glucose equivalent and 3.39 g/L/h, respectively. SA production could be further increased to 90.68 g/L with the yield and overall productivity of 1.15 mol/mol glucose equivalent and 3.49 g/L/h, respectively, by utilizing a mixture of magnesium hydroxide and ammonia solution as a pH controlling solution. Furthermore, formation of byproducts was drastically reduced, resulting in almost homo-fermentative SA production. This allowed the recovery and purification of SA to a high purity (99.997%) with a high recovery yield (74.65%) through simple downstream processes composed of decolorization, vacuum distillation, and crystallization. The SA producer and processes developed in this study will allow economical production of SA in an industrial-scale. Biotechnol. Bioeng. 2016;113: 2168-2177. © 2016 Wiley Periodicals, Inc. PMID:27070659

  19. Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure. Heart failure was induced in rats by myocardial infarction, and mitochondria were isolated from hearts by differential centrifugation. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts. Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism. Among those, the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunits while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex. These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.

  20. Is the habitation of acidic-water sanctuaries by galaxiid fish facilitated by natural organic matter modification of sodium metabolism?

    Science.gov (United States)

    Glover, Chris N; Donovan, Katherine A; Hill, Jonathan V

    2012-01-01

    Acidic waters of New Zealand's West Coast are hypothesized to be a refuge for native galaxiid fish, allowing them to escape predation from acid-sensitive invasive salmonid species. To determine the mechanisms by which galaxiids tolerate low pH, we investigated sodium metabolism in inanga Galaxias maculatus in response to water pH, short-term acclimation to acidic waters, the presence and source of natural organic matter (NOM), and fish life history. Contrary to expectation, inanga were physiologically sensitive to acid exposure, displaying inhibited sodium influx and exacerbated sodium efflux. Short-term (144 h) acclimation to acid did not modify this effect, and NOM did not exert a protective effect on sodium metabolism at low pH. Inanga sourced from naturally acidic West Coast waters did, however, display a sodium influx capacity (J(max)) that was significantly elevated when compared with that of fish collected from neutral waters. All inanga, independent of source, exhibited exceptionally high sodium uptake affinities (18-40 μM) relative to previously studied freshwater teleosts. Although inanga displayed relatively poor physiological tolerance to acidic waters, their high sodium influx affinity coupled with their occupation of near-coastal waters with elevated sodium levels may permit habitation of low-pH freshwaters. PMID:22902374

  1. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats.

    Science.gov (United States)

    Rincón-Cervera, Miguel Ángel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Barrera, Cynthia; Espinosa, Alejandra; Marambio, Macarena; Valenzuela, Alfonso

    2016-08-01

    Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA. PMID:26995676

  2. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats.

    Science.gov (United States)

    Rincón-Cervera, Miguel Ángel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Barrera, Cynthia; Espinosa, Alejandra; Marambio, Macarena; Valenzuela, Alfonso

    2016-08-01

    Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA.

  3. A CAD/CAM interface for computer-aided design of cams

    OpenAIRE

    Gandhi, Ashit R.

    1985-01-01

    The purpose of this thesis is to provide a complete package for the design and three dimensional modeling display of cams. The software produced as a part of this work will operate as a module of CADAM to produce cam designs and enter the resulting cam as a CAD model and produce the graphical display of the cam. In addition to the introductory material, this thesis is divided into four sections. The section on the graphics packages used in this thesis includes a b...

  4. AFSC/FMA/CAMS Data Objects

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The CAMS system consists of a set of tables and packages that provide authentication services to all other North Pacific Groundfish and Halibut Observing Program...

  5. The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats.

    Science.gov (United States)

    Engskog, Mikael K R; Karlsson, Oskar; Haglöf, Jakob; Elmsjö, Albert; Brittebo, Eva; Arvidsson, Torbjörn; Pettersson, Curt

    2013-10-01

    The neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) is produced by most cyanobacteria. BMAA is considered as a potential health threat because of its putative role in neurodegenerative diseases. We have previously observed cognitive disturbances and morphological brain changes in adult rodents exposed to BMAA during the development. The aim of this study was to characterize changes of major intermediary metabolites in serum following neonatal exposure to BMAA using a non-targeted metabolomic approach. NMR spectroscopy was used to obtain serum metabolic profiles from neonatal rats exposed to BMAA (40, 150, 460mg/kg) or vehicle on postnatal days 9-10. Multivariate data analysis of binned NMR data indicated metabolic pattern differences between the different treatment groups. In particular five metabolites, d-glucose, lactate, 3-hydroxybutyrate, creatine and acetate, were changed in serum of BMAA-treated neonatal rats. These metabolites are associated with changes in energy metabolism and amino acid metabolism. Further statistical analysis disclosed that all the identified serum metabolites in the lowest dose group were significantly (pmodel used in this study is so far the only animal model that displays significant biochemical and behavioral effects after a low short-term dose of BMAA. The demonstrated perturbation of intermediary metabolism may contribute to BMAA-induced developmental changes that result in long-term effects on adult brain function.

  6. A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes

    DEFF Research Database (Denmark)

    Bouyakdan, Khalil; Taïb, Bouchra; Budry, Lionel;

    2015-01-01

    Acyl-CoA-binding protein (ACBP) is a ubiquitously expressed protein that binds intracellular acyl-CoA esters. Several studies have suggested that ACBP acts as an acyl-CoA pool former and regulates long-chain fatty acids (LCFA) metabolism in peripheral tissues. In the brain, ACBP is known as Diaze......-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol....... metabolism-related gene expression using ACBP-deficient and control mice. ACBP was mainly found in astrocytes with high expression levels in the mediobasal hypothalamus. We demonstrate that ACBP deficiency alters the central LCFA-CoA profile and impairs unsaturated (oleate, linolenate) but not saturated...... (palmitate, stearate) LCFA metabolic fluxes in hypothalamic slices and astrocyte cultures. In addition, lack of ACBP differently affects the expression of genes involved in FA metabolism in cortical versus hypothalamic astrocytes. Finally, ACBP deficiency increases FA content and impairs their release...

  7. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Bell, Lauren N.; Karoly, Edward D.; Freeman, Gordon J.; Petkova, Victoria; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.

    2015-01-01

    During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade. PMID:25809635

  8. Model Documentation for the MiniCAM

    Energy Technology Data Exchange (ETDEWEB)

    Brenkert, Antoinette L.; Smith, Steven J.; Kim, Son H.; Pitcher, Hugh M.

    2003-07-17

    The MiniCAM, short for the Mini-Climate Assessment Model, is an integrated assessment model of moderate complexity focused on energy and agriculture sectors. The model produces emissions of greenhouse gases (carbon dioxide, methane and nitrous oxide) and other radiatively important substances such as sulfur dioxide. Through incorporation of the simple climate model MAGICC, the consequences of these emissions for climate change and sea-level rise can be examined. The MiniCAM is designed to be fast and flexible.

  9. Radiometric Calibration for AgCam

    OpenAIRE

    Edward Hildum; Lianbo Hu; Hojin Kim; Xiaodong Zhang; Changyong Dou; Doug Olsen

    2010-01-01

    The student-built Agricultural Camera (AgCam) now onboard the International Space Station observes the Earth surface through two linescan cameras with Charge-Coupled Device (CCD) arrays sensitive to visible and near-infrared wavelengths, respectively. The electro-optical components of the AgCam were characterized using precision calibration equipment; a method for modeling and applying these measurements was derived. Correction coefficients to minimize effects of optical vignetting, CCD non-u...

  10. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation

    DEFF Research Database (Denmark)

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian;

    2015-01-01

    and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards......Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process....... Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found...

  11. Serum uric acid and disorders of glucose metabolism: the role of glycosuria

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, J.A.M. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Kang, H.C. [Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Greffin, S. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Garcia Rosa, M.L. [Departamento de Epidemiologia e Bioestatística, Universidade Federal Fluminense, Niterói, RJ (Brazil); Lugon, J.R. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2014-08-22

    Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

  12. Nicotinic acid supplementation in diet favored intramuscular fat deposition and lipid metabolism in finishing steers.

    Science.gov (United States)

    Yang, Zhu-Qing; Bao, Lin-Bin; Zhao, Xiang-Hui; Wang, Can-Yu; Zhou, Shan; Wen, Lu-Hua; Fu, Chuan-Bian; Gong, Jian-Ming; Qu, Ming-Ren

    2016-06-01

    Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH, participates in many biochemical processes, e.g. lipid metabolism. The main purpose of this study was to investigate the effects of dietary NA on carcass traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred finishing steers. Sixteen steers with the similar body weight and at the age of 24 months were randomly allocated into control group (feeding basal diet) and NA group (feeding basal diet + 1000 mg/kg NA). All experimental cattle were fed a 90% concentrate diet and 10% forage straw in a 120-day feeding experiment. The results showed that supplemental NA in diet increased longissimus area, intramuscular fat content (17.14% vs. 9.03%), marbling score (8.08 vs. 4.30), redness (a*), and chroma (C*) values of LD muscle, but reduced carcass fat content (not including imtramuscular fat), pH24 h and moisture content of LD muscle, along with no effect on backfat thickness. Besides, NA supplementation increased serum HDL-C concentration, but decreased the serum levels of LDL-C, triglyceride, non-esterified fatty acid, total cholesterol, and glycated serum protein. In addition, NA supplementation increased G6PDH and ICDH activities of LD muscle. These results suggested that NA supplementation in diet improves the carcass characteristics and beef quality, and regulates the compositions of serum metabolites. Based on the above results, NA should be used as the feed additive in cattle industry. PMID:27048556

  13. Computational Modeling of Competitive Metabolism between ω3- and ω6-Polyunsaturated Fatty Acids in Inflammatory Macrophages.

    Science.gov (United States)

    Gupta, Shakti; Kihara, Yasuyuki; Maurya, Mano R; Norris, Paul C; Dennis, Edward A; Subramaniam, Shankar

    2016-08-25

    Arachidonic acid (AA), a representative ω6-polyunsaturated fatty acid (PUFA), is a precursor of 2-series prostaglandins (PGs) that play important roles in inflammation, pain, fever, and related disorders including cardiovascular diseases. Eating fish or supplementation with the ω3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is widely assumed to be beneficial in preventing cardiovascular diseases. A proposed mechanism for a cardio-protective role of ω3-PUFAs assumes competition between AA and ω3-PUFAs for cyclooxygenases (COX), leading to reduced production of 2-series PGs. In this study, we have used a systems biology approach to integrate existing knowledge and novel high-throughput data that facilitates a quantitative understanding of the molecular mechanism of ω3- and ω6-PUFA metabolism in mammalian cells. We have developed a quantitative computational model of the competitive metabolism of AA and EPA via the COX pathway through a two-step matrix-based approach to estimate the rate constants. This model was developed by using lipidomic data sets that were experimentally obtained from EPA-supplemented ATP-stimulated RAW264.7 macrophages. The resulting model fits the experimental data well for all metabolites and demonstrates that the integrated metabolic and signaling networks and the experimental data are consistent with one another. The robustness of the model was validated through parametric sensitivity and uncertainty analysis. We also validated the model by predicting the results from other independent experiments involving AA- and DHA-supplemented ATP-stimulated RAW264.7 cells using the parameters estimated with EPA. Furthermore, we showed that the higher affinity of EPA binding to COX compared with AA was able to inhibit AA metabolism effectively. Thus, our model captures the essential features of competitive metabolism of ω3- and ω6-PUFAs. PMID:27063350

  14. Soil metabolic transformations of carbon-14-myo-inositol, carbon-14-phytic acid and carbon-14-iron(III) phytate

    International Nuclear Information System (INIS)

    Uniformly labelled 14C-phytic acid and 14C-iron(III) phytate were synthesized from uniformly labelled 14C-myo-inositol. The three compounds were incubated in an Andosol sandy loam at 70% field capacity and 36.50C for a 12-day period. Myo-inositol, phytic acid and iron(III) phytate underwent a 61.0, 1.9 and 0% microbial oxidation respectively to CO2 during the incubation period. The rate of fixation of 14C-phytic acid was illustrated by its rapid decline in metabolism in the 12-day period. The metabolism rate of phytic was considerably reduced by the presumed formation of iron(III) and aluminium phytate. The metabolism rate of myo-inositol was reduced nine-fold after an initial rapid metabolism during the first day of incubation. The following mechanisms were observed in the soil metabolism of myo-inositol: (1) soil mineral-inositol carbon adsorption, (2) humic acid-inositol carbon adsorption, (3) the phosphorylation of myo-inositol, and (4) the epimerization of myo-inositol to chiro-inositol. The formation of (1) and (2) was found to be highly dependent upon microbial activity. Interactions (1), (2) and (3)are considered as possible mechanisms for the inhibition of the microbial oxidation of myo-inositol. The inhibition of myo-inositol oxidation via adsorption or phosphorylation is considered to be due to the chemical blockage of the stereo-specific microbial oxidative attack on the axial hydroxyl group. (author)

  15. [Influence of exogenous gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid contents in roots of melon seedling under hypoxia stress].

    Science.gov (United States)

    Wang, Chun-Yan; Li, Jing-Rui; Xia, Qing-Ping; Wu, Xiao-Lei; Gao, Hong-Bo

    2014-07-01

    This paper investigated the influence of gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid content under hypoxia stress by accurately controlling the level of dissolved oxygen in hydroponics, using the roots of melon 'Xiyu 1' seedlings as the test material. The results showed that compared with the control, the growth of roots was inhibited seriously under hypoxia stress. Meanwhile, the hypoxia-treated roots had significantly higher activities of glutamate decarboxylase (GAD), glutamate dehydrogenase (GDH), glutamate synthase (GOGAT), glutamine synthetase (GS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the contents of GABA, pyruvic acid, alanine (Ala) and aspartic acid (Asp). But the contents of glutamic acid (Glu) and alpha-keto glutaric acid in roots under hypoxia stress was obviously lower than those of the control. Exogenous treatment with GABA alleviated the inhibition effect of hypoxia stress on root growth, which was accompanied by an increase in the contents of endogenous GABA, Glu, alpha-keto glutaric acid and Asp. Furthermore, under hypoxia stress, the activities of GAD, GDH, GOGAT, GS, ALT, AST as well as the contents of pyruvic acid and Ala significantly decreased in roots treated with GABA. However, adding GABA and viny-gamma-aminobutyric acid (VGB) reduced the alleviation effect of GABA on melon seedlings under hypoxia stress. The results suggested that absorption of GABA by roots could alleviate the injury of hypoxia stress to melon seedlings. This meant that GABA treatment allows the normal physiological metabolism under hypoxia by inhibiting the GAD activity through feedback and maintaining higher Glu content as well as the bal- ance of carbon and nitrogen.

  16. Chiropractic and CAM Utilization: A Descriptive Review

    Directory of Open Access Journals (Sweden)

    Meeker William C

    2007-01-01

    Full Text Available Abstract Objective To conduct a descriptive review of the scientific literature examining use rates of modalities and procedures used by CAM clinicians to manage chronic LBP and other conditions Data Sources A literature of PubMed and MANTIS was performed using the key terms Chiropractic; Low Back Pain; Utilization Rate; Use Rate; Complementary and Alternative Medicine; and Health Services in various combinations. Data Selection A total of 137 papers were selected, based upon including information about chiropractic utilization, CAM utilization and low back pain and other conditions. Data Synthesis Information was extracted from each paper addressing use of chiropractic and CAM, and is summarized in tabular form. Results Thematic analysis of the paper topics indicated that there were 5 functional areas covered by the literature: back pain papers, general chiropractic papers, insurance-related papers, general CAM-related papers; and worker's compensation papers. Conclusion Studies looking at chiropractic utilization demonstrate that the rates vary, but generally fall into a range from around 6% to 12% of the population, most of whom seek chiropractic care for low back pain and not for organic disease or visceral dysfunction. CAM is itself used by people suffering from a variety of conditions, though it is often used not as a primary intervention, but rather as an additional form of care. CAM and chiropractic often offer lower costs for comparable results compared to conventional medicine.

  17. Statistical Shape Modeling of Cam Femoroacetabular Impingement

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Michael D.; Dater, Manasi; Whitaker, Ross; Jurrus, Elizabeth R.; Peters, Christopher L.; Anderson, Andrew E.

    2013-10-01

    In this study, statistical shape modeling (SSM) was used to quantify three-dimensional (3D) variation and morphologic differences between femurs with and without cam femoroacetabular impingement (FAI). 3D surfaces were generated from CT scans of femurs from 41 controls and 30 cam FAI patients. SSM correspondence particles were optimally positioned on each surface using a gradient descent energy function. Mean shapes for control and patient groups were defined from the resulting particle configurations. Morphological differences between group mean shapes and between the control mean and individual patients were calculated. Principal component analysis was used to describe anatomical variation present in both groups. The first 6 modes (or principal components) captured statistically significant shape variations, which comprised 84% of cumulative variation among the femurs. Shape variation was greatest in femoral offset, greater trochanter height, and the head-neck junction. The mean cam femur shape protruded above the control mean by a maximum of 3.3 mm with sustained protrusions of 2.5-3.0 mm along the anterolateral head-neck junction and distally along the anterior neck, corresponding well with reported cam lesion locations and soft-tissue damage. This study provides initial evidence that SSM can describe variations in femoral morphology in both controls and cam FAI patients and may be useful for developing new measurements of pathological anatomy. SSM may also be applied to characterize cam FAI severity and provide templates to guide patient-specific surgical resection of bone.

  18. A metabolic model of the mitochondrion and its use in modelling diseases of the tricarboxylic acid cycle

    Directory of Open Access Journals (Sweden)

    Robinson Alan J

    2011-06-01

    Full Text Available Abstract Background Mitochondria are a vital component of eukaryotic cells and their dysfunction is implicated in a large number of metabolic, degenerative and age-related human diseases. The mechanism or these disorders can be difficult to elucidate due to the inherent complexity of mitochondrial metabolism. To understand how mitochondrial metabolic dysfunction contributes to these diseases, a metabolic model of a human heart mitochondrion was created. Results A new model of mitochondrial metabolism was built on the principle of metabolite availability using MitoMiner, a mitochondrial proteomics database, to evaluate the subcellular localisation of reactions that have evidence for mitochondrial localisation. Extensive curation and manual refinement was used to create a model called iAS253, containing 253 reactions, 245 metabolites and 89 transport steps across the inner mitochondrial membrane. To demonstrate the predictive abilities of the model, flux balance analysis was used to calculate metabolite fluxes under normal conditions and to simulate three metabolic disorders that affect the TCA cycle: fumarase deficiency, succinate dehydrogenase deficiency and α-ketoglutarate dehydrogenase deficiency. Conclusion The results of simulations using the new model corresponded closely with phenotypic data under normal conditions and provided insight into the complicated and unintuitive phenotypes of the three disorders, including the effect of interventions that may be of therapeutic benefit, such as low glucose diets or amino acid supplements. The model offers the ability to investigate other mitochondrial disorders and can provide the framework for the integration of experimental data in future studies.

  19. Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice.

    Science.gov (United States)

    Pierre, Joseph F; Martinez, Kristina B; Ye, Honggang; Nadimpalli, Anuradha; Morton, Timothy C; Yang, Jinghui; Wang, Qiang; Patno, Noelle; Chang, Eugene B; Yin, Deng Ping

    2016-08-01

    The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1α, PGC-1β, and PDGFRα in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype. PMID:27340128

  20. Impact of Inhibiting Ileal Apical Versus Basolateral Bile acid Transport on Cholesterol Metabolism and Atherosclerosis in Mice

    Science.gov (United States)

    Dawson, Paul A.

    2015-01-01

    Background Bile acid sequestrants have been used for many years to treat hypercholesterolemia by increasing hepatic conversion of cholesterol to bile acids, thereby inducing hepatic LDL receptor expression and clearance of apoB-containing particles. In order to further understand the underlying molecular mechanisms linking gut-liver signaling and cholesterol homeostasis, mouse models defective in ileal apical membrane bile acid transport (Asbt null) and ileal basolateral membrane bile acid transport (Ostα null) were studied under basal and hypercholesterolemic conditions. Key Messages Hepatic conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism and a major mechanism for cholesterol elimination. Blocking ileal apical membrane bile acid transport (Asbt null mice) increases fecal bile acid excretion, hepatic Cyp7a1 expression and the relative proportion of taurocholate in the bile acid pool, but decreases ileal FGF15 expression, bile acid pool size, and hepatic cholesterol content. In contrast, blocking ileal basolateral membrane bile acid transport (Ostα null mice) increases ileal FGF15 expression, reduces hepatic Cyp7a1 expression, and increases the proportion of tauro-β-muricholic acid in the bile acid pool. In the hypercholesterolemic apoE null background, plasma cholesterol levels and measurements of atherosclerosis were reduced in Asbt/apoE null mice but not in Ostα/apoE null mice. Conclusions Blocking intestinal absorption of bile acids at the apical versus basolateral membrane differentially affects bile acid and cholesterol metabolism, including the development of hypercholesterolemia-associated atherosclerosis. The molecular mechanism likely involves altered regulation of ileal FGF15 expression. PMID:26045273