62 results
Search Results
2. Amino acid transport by the small intestine of the rat. Evidence against interactions between sugars and amino acids at the carrier level.
- Author
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Munck BG
- Subjects
- Animals, Biological Transport, Carbon Isotopes, Chromatography, Paper, Galactose metabolism, Intestinal Mucosa, Intestinal Secretions, Leucine metabolism, Male, Rats, Serous Membrane, Amino Acids metabolism, Carbohydrate Metabolism, Intestine, Small metabolism
- Published
- 1968
- Full Text
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3. Development of sugar and amino acid transport by intestine and yolk sac of the guinea pig.
- Author
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Butt JH 2nd and Wilson TH
- Subjects
- Animals, Animals, Newborn metabolism, Biological Transport, Active, Carbon Isotopes, Chromatography, Paper, Female, Guinea Pigs, Pregnancy, Amino Acids metabolism, Carbohydrate Metabolism, Fetus metabolism, Intestine, Small metabolism, Ovum metabolism
- Published
- 1968
- Full Text
- View/download PDF
4. Cell cycle and post cycle changes during continuous phased growth of Candida utilis.
- Author
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Dawson PS
- Subjects
- Amino Acids analysis, Ammonia analysis, Ammonia metabolism, Candida growth & development, Carbohydrates analysis, Chromatography, Paper, Chromatography, Thin Layer, Glucose analysis, Glucose metabolism, Glycogen analysis, Glycogen metabolism, Lipids analysis, Phospholipids analysis, Phospholipids metabolism, Polysaccharides analysis, Polysaccharides metabolism, Amino Acids metabolism, Candida metabolism, Carbohydrate Metabolism, Culture Media, Lipid Metabolism
- Published
- 1970
- Full Text
- View/download PDF
5. The central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome
- Author
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Gelpi, Marco, Mikaeloff, Flora, Knudsen, Andreas D., Benfeitas, Rui, Krishnan, Shuba, Akusjärvi, Sara Svenssson, Høgh, Julie, Murray, Daniel D., Ullum, Henrik, Neogi, Ujjwal, and Nielsen, Susanne D.
- Subjects
Male ,Metabolic Syndrome ,Anti-HIV Agents ,antiretroviral therapy ,Glutamic Acid ,HIV Infections ,Middle Aged ,immune-phenotyping ,metabolomics ,metabolic syndrome ,Carbohydrate Metabolism ,Humans ,Female ,Amino Acids ,HIV-infection ,Research Paper - Abstract
Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n= 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS (n= 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate
- Published
- 2021
6. A.S.P.E.N. 2003 Research Workshop on using tracers to measure carbohydrate, fat, and amino acid metabolism in humans.
- Author
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Parks EJ and Matthews DE
- Subjects
- Animals, Biological Transport, Fatty Acids metabolism, Gluconeogenesis, Glucose metabolism, Humans, Kinetics, Magnetic Resonance Spectroscopy, Amino Acids metabolism, Carbohydrate Metabolism, Isotopes, Lipid Metabolism
- Abstract
The 2003 A.S.P.E.N. Research Workshop was held during Nutrition Week on January 18 in San Antonio, Texas. The workshop brought scientists and clinicians from around the world together to discuss the latest developments in methodology to measure substrate use and flux in vivo. Methods presented were designed to track the fate of nutrients that are given orally, enterally, or parentally to humans. Talks presented a variety of approaches to tackle particularly difficult problems of assessing intracellular processes in vivo in living animals and humans. The present paper reviews those various approaches that have been developed using (i) differential administration of tracers across organ beds to define organ-specific intracellular metabolism without tissue biopsies; (ii) animal models that will tolerate complicated multicatheter placement situations; (iii) methods that take advantage of complicated pathways of metabolism that allow movement of specific portions of a molecule for determining gluconeogenesis; (iv) nuclear magnetic resonance and in vivo magnetic resonance spectroscopy to measure intramolecular distribution of tracers; and (v) the multiple stable isotope approach to follow biosynthetic pathways associated with fatty acid flux in the fed-state in humans. Improved accessibility of these methods provides much hope for their expanded use in understanding the basic mechanisms of metabolic regulation and the physiologic changes in nutrient use that occur in disease states.
- Published
- 2004
- Full Text
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7. Metabolomic profiling identifies pathways associated with minimal residual disease in childhood acute lymphoblastic leukaemia
- Author
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Jacob J. Junco, Karen R. Rabin, Jeremy M. Schraw, Philip J. Lupo, Austin L. Brown, and Michael E. Scheurer
- Subjects
Male ,0301 basic medicine ,Oncology ,Neoplasm, Residual ,Research paper ,Epidemiology ,Nicotinamide phosphoribosyltransferase ,lcsh:Medicine ,Disease ,NAMPT ,chemistry.chemical_compound ,0302 clinical medicine ,Immunophenotyping ,Amino Acids ,Child ,lcsh:R5-920 ,Hematology ,Acute lymphoblastic leukaemia ,General Medicine ,3. Good health ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,Metabolome ,Carbohydrate Metabolism ,Female ,lcsh:Medicine (General) ,Metabolic Networks and Pathways ,medicine.medical_specialty ,General Biochemistry, Genetics and Molecular Biology ,Biological pathway ,03 medical and health sciences ,Cell Line, Tumor ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Metabolomics ,Cancer prevention ,business.industry ,Minimal residual disease ,lcsh:R ,Genetic Variation ,030104 developmental biology ,ROC Curve ,chemistry ,NAMPT inhibitors ,Bone marrow ,business - Abstract
Background: End-induction minimal residual disease (MRD) is the strongest predictor of relapse in paediatric acute lymphoblastic leukaemia (ALL), but an understanding of the biological pathways underlying early treatment response remains elusive. We hypothesized that metabolomic profiling of diagnostic bone marrow plasma could provide insights into the underlying biology of early treatment response and inform treatment strategies for high-risk patients. Methods: We performed global metabolomic profiling of samples from discovery (N = 93) and replication (N = 62) cohorts treated at Texas Children's Hospital. Next, we tested the cytotoxicity of drugs targeting central carbon metabolism in cell lines and patient-derived xenograft (PDX) cells. Findings: Metabolite set enrichment analysis identified altered central carbon and amino acid metabolism in MRD-positive patients from both cohorts at a 5% false discovery rate. Metabolites from these pathways were used as inputs for unsupervised hierarchical clustering. Two distinct clusters were identified, which were independently associated with MRD after adjustment for immunophenotype, cytogenetics, and NCI risk group. Three nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which reduce glycolytic/TCA cycle activities, demonstrated nanomolar-range cytotoxicity in B- and T-ALL cell lines and PDX cells. Interpretation: This study provides new insights into the role of central carbon metabolism in early treatment response and as a potential targetable pathway in high-risk disease. Funding: American Society of Hematology; Baylor College of Medicine Department of Paediatrics; Cancer Prevention and Research Institute of Texas; the Lynch family; St. Baldrick's Foundation with support from the Micaela's Army Foundation; United States National Institutes of Health. Keywords: Acute lymphoblastic leukaemia, Minimal residual disease, Epidemiology, NAMPT, NAMPT inhibitors
- Published
- 2019
8. CO2 Production by Extracts of Hymenolepis diminuta (Cestoda: Hymenolepididae) with Aspartate and α-Ketoglutarate as Substrates
- Author
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Hicks, Terrell C. and Ubelaker, John E.
- Published
- 1973
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9. Evidence for Transaminase Activity in the Slime Mold, Dictyostelium discoideum Raper
- Author
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Krivanek, Jerome O. and Krivanek, Robin C.
- Published
- 1965
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10. Chromatographic Analyses of Amino Acids in the Developing Slime Mold, Dictyostelium discoideum Raper
- Author
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Krivanek, Jerome O. and Krivanek, Robin C.
- Published
- 1959
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11. An update of fetal and placental metabolism: carbohydrate and amino acids.
- Author
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Battaglia FC
- Subjects
- Carbohydrates biosynthesis, Female, Humans, Lactates biosynthesis, Lactic Acid, Liver embryology, Liver metabolism, Nutritional Physiological Phenomena, Pregnancy, Amino Acids metabolism, Carbohydrate Metabolism, Fetus metabolism, Placenta metabolism
- Abstract
This paper presents a review of fetal and placental metabolism, particularly as it relates to carbohydrate and amino acid metabolism. The strengths of simultaneous application of the Fick principle methodology for the determination of net substrate fluxes with tracer methodology for estimating rates of fetal and placental utilization of compounds is discussed and illustrated. The interconversion of nutrients, both within the fetus and in the placenta, is reviewed with particular emphasis on potential cycling of nutrients between the placenta and fetal liver. Recent work defining the changes in fetal and placental metabolism at mid gestation is also discussed. This work is used as an example illustrating the importance of defining a wide gestational age window for study of ontogenetic changes in fetal metabolism. Finally, recent clinical studies utilizing cordocentesis or periumbilical blood sampling for evaluating the biochemical environment of the human fetus at mid gestation are reviewed and compared to data obtained under chronic steady-state conditions in fetal sheep.
- Published
- 1989
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12. Carbohydrate effects of amino acid transport by Trypanosoma equiperdum.
- Author
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Jackson PR and Fisher FM Jr
- Subjects
- Alanine biosynthesis, Animals, Biological Transport, Glucose metabolism, Glutamates metabolism, Iodoacetates pharmacology, Lysine metabolism, Methionine metabolism, Phenylalanine metabolism, Proline metabolism, Amino Acids metabolism, Carbohydrate Metabolism, Trypanosoma metabolism
- Abstract
Uptake of 14C-labeled alanine, glutamate, lysine, methionine, proline, and phenylalanine by Trypanosoma equiperdum during 2-minute incubations occurred by diffusion and membrane-mediated processes. Amino acid metabolism was not detected by paper chromatography of trypanosome extracts. Most of 18 carbohydrates tested for ability to alter amino acid transport neither changed nor significantly inhibited transport. Glucose, however, stimulated glutamate, lysine and proline transport; fructose stimulated lysine uptake and 2-deoxy-D-glucose increased phenylalanine and methionine absorption. No evidence was found that the carbohydrates acted by binding to amino acid transport "sites." Glucose inhibition of alanine, phenylalanine, and methionine uptake was linked to glycolysis. The rapid formation of alanine form glucose stimulated alanine release and, when glycolysis was blocked, glucose no longer inhibited alanine transport. Methionine and phenylalanine release was also stimulated by glucose. Glucose changed the ability of lysine, glutamate, and proline to inhibit each others' uptake, indicating that certain amino acids are preferentially absorbed by respiring cells. Analysis of free pool amino acid levels suggested that some amino acid transport systems in T. equiperdum are linked in such a way to glycolysis as to control the cell concentrations of these amino acids.
- Published
- 1977
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13. The genome sequence of the highly acetic acid-tolerant zygosaccharomyces bailii-derived interspecies hybrid strain ISA1307, isolated from a sparkling wine plant
- Author
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Filipa Dias-Valada, Ulrich Güldener, Margarida Palma, Cecília Leão, Joana F. Guerreiro, Júlia Santos, Isabel Sá-Correia, Maria João Sousa, Fernando Rodrigues, Nuno P. Mira, Filipa de Canaveira Roque, Martin Münsterkötter, and Universidade do Minho
- Subjects
Zygosaccharomyces bailii ,genome sequencing and annotation ,hybrid yeast strains ,weak acid food preservatives tolerance ,wine yeast strains ,Wine ,Zygosaccharomyces ,Genome ,Weak acid food preservatives tolerance ,Fungal Proteins ,Wine yeast strains ,Stress, Physiological ,Genetics ,Amino Acids ,DNA, Fungal ,Molecular Biology ,Genome size ,Gene ,Acetic Acid ,2. Zero hunger ,Whole genome sequencing ,Fungal protein ,Genome sequencing and annotation ,Science & Technology ,biology ,Base Sequence ,Chimera ,Chromosome Mapping ,Biological Transport ,Molecular Sequence Annotation ,General Medicine ,Full Papers ,biology.organism_classification ,Genes, Mating Type, Fungal ,Yeast ,Meiosis ,Hybrid yeast strains ,Karyotyping ,Carbohydrate Metabolism ,Genome, Fungal - Abstract
In this work, it is described the sequencing and annotation of the genome of the yeast strain ISA1307, isolated from a sparkling wine continuous production plant. This strain, formerly considered of the Zygosaccharomyces bailii species, has been used to study Z. bailii physiology, in particular, its extreme tolerance to acetic acid stress at low pH. The analysis of the genome sequence described in this work indicates that strain ISA1307 is an interspecies hybrid between Z. bailii and a closely related species. The genome sequence of ISA1307 is distributed through 154 scaffolds and has a size of around 21.2 Mb, corresponding to 96% of the genome size estimated by flow cytometry. Annotation of ISA1307 genome includes 4385 duplicated genes (~90% of the total number of predicted genes) and 1155 predicted single-copy genes. The functional categories including a higher number of genes are 'Metabolism and generation of energy', 'Protein folding, modification and targeting' and 'Biogenesis of cellular components'. The knowledge of the genome sequence of the ISA1307 strain is expected to contribute to accelerate systems-level understanding of stress resistance mechanisms in Z. bailii and to inspire and guide novel biotechnological applications of this yeast species/strain in fermentation processes, given its high resilience to acidic stress. The availability of the ISA1307 genome sequence also paves the way to a better understanding of the genetic mechanisms underlying the generation and selection of more robust hybrid yeast strains in the stressful environment of wine fermentations., This research was supported by FCT and FEDER through POFC-COMPETE [contracts PEst-OE/EQB/ LA0023/2011_ research line: Systems and Synthetic Biology PTDC/AGR-ALI/102608/2008, PEst-C/BIA/ UI4050/2011, and post-doctoral grant to M.P. (SFRH/BPD/73306/2010) and PhD grants to J.F.G. (SFRH/ BD/80065/2011) and F.C.R. (SFRH/BD/82226/2011)]. U.G. acknowledges the Austrian Science Fund (FWF, special research project F3705).
- Published
- 2014
14. Proteomic and phosphoproteomic analysis of polyethylene glycol-induced osmotic stress in root tips of common bean (Phaseolus vulgaris L.)
- Author
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Idupulapati M. Rao, Dejene Eticha, Walter J. Horst, Alain Van Dorsselaer, Barbara Schlingmann, Dimitri Heintz, Hendrik Führs, Zhong-Bao Yang, Daniel Ayoub, and Hans-Peter Braun
- Subjects
root tips ,dehydrin ,Osmotic shock ,Physiology ,low water potentials ,ionically bound proteins ,Plant Science ,arabidopsis-thaliana ,Proteomics ,Plant Roots ,dehydrin-like proteins ,Polyethylene Glycols ,Cell wall ,Transcriptome ,proteomics ,salt-responsive proteins ,Osmotic Pressure ,s-adenosylmethionine synthetase ,Electrophoresis, Gel, Two-Dimensional ,Amino Acids ,Dewey Decimal Classification::500 | Naturwissenschaften ,cell-wall proteome ,nadp(+)-dependent isocitrate dehydrogenase ,elongation zone ,Plant Proteins ,Phaseolus ,common bean ,biology ,Phosphoproteomics ,phosphoproteomics ,biology.organism_classification ,Phosphoproteins ,apoplast ,maize primary root ,Metabolic pathway ,Biochemistry ,Proteome ,Carbohydrate Metabolism ,cell wall ,ddc:500 ,Research Paper - Abstract
Previous studies have shown that polyethylene glycol (PEG)-induced osmotic stress (OS) reduces cell-wall (CW) porosity and limits aluminium (Al) uptake by root tips of common bean (Phaseolus vulgaris L.). A subsequent transcriptomic study suggested that genes related to CW processes are involved in adjustment to OS. In this study, a proteomic and phosphoproteomic approach was applied to identify OS-induced protein regulation to further improve our understanding of how OS affects Al accumulation. Analysis of total soluble proteins in root tips indicated that, in total, 22 proteins were differentially regulated by OS; these proteins were functionally categorized. Seventy-seven per- cent of the total expressed proteins were involved in metabolic pathways, particularly of carbohydrate and amino acid metabolism. An analysis of the apoplastic proteome revealed that OS reduced the level of five proteins and increased that of seven proteins. Investigation of the total soluble phosphoproteome suggested that dehydrin responded to OS with an enhanced phosphorylation state without a change in abundance. A cellular immunolocalization analysis indicated that dehydrin was localized mainly in the CW. This suggests that dehydrin may play a major protective role in the OS-induced physical breakdown of the CW structure and thus maintenance of the reversibility of CW extensibility during recovery from OS. The proteomic and phosphoproteomic analyses provided novel insights into the complex mechanisms of OS-induced reduction of Al accumulation in the root tips of common bean and highlight a key role for modification of CW structure. BMZ/GTZ/05.7860.9-001.00 BMZ/GTZ/05.7860.9-001.00
- Published
- 2013
15. Atlas of Rice Grain Filling-Related Metabolism under High Temperature: Joint Analysis of Metabolome and Transcriptome Demonstrated Inhibition of Starch Accumulation and Induction of Amino Acid Accumulation
- Author
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Makoto Hakata and Hiromoto Yamakawa
- Subjects
Hot Temperature ,Grain filling ,Starch ,Physiology ,Plant Science ,RNA, Transfer, Amino Acyl ,Biology ,Mass Spectrometry ,Caryopsis ,chemistry.chemical_compound ,Gene Expression Regulation, Plant ,Glycolysis ,Amino Acids ,Oligonucleotide Array Sequence Analysis ,chemistry.chemical_classification ,Gene Expression Profiling ,Regular Papers ,Electrophoresis, Capillary ,food and beverages ,Oryza ,Metabolism ,Cell Biology ,General Medicine ,High temperature ,Amino acid ,Metabolic pathway ,chemistry ,Gluconeogenesis ,Biochemistry ,RNA, Plant ,Seeds ,Metabolome ,Carbohydrate Metabolism ,Gene expression ,Rice ,Pyruvic acid ,Corrigendum - Abstract
High temperature impairs grain filling by inhibiting the deposition of storage materials such as starch and protein. To comprehend its impact on grain filling metabolism in rice (Oryza sativa), levels of metabolites and transcripts related to central pathways of metabolism were simultaneously determined in developing caryopses exposed to high temperature (33 degrees C/28 degrees C) and a control temperature (25 degrees C/20 degrees C) during the milky stage. A capillary electrophoresis-based metabolomic analysis revealed that high temperature increased the accumulation of sucrose and pyruvate/ oxaloacetate-derived amino acids and decreased levels of sugar phosphates and organic acids involved in glycolysis/gluconeogenesis and the tricarboxylic acid (TCA) cycle, respectively. A transcriptomic analysis using a whole genome-covering microarray unraveled the possible metabolic steps causing the shortage of storage materials under the elevated temperature. Starch deposition might be impaired by down-regulation of sucrose import/degradation and starch biosynthesis, and/or up-regulation of starch degradation as well as inefficient ATP production by an inhibited cytochrome respiration chain, as indicated by the response of gene expression to high temperature. Amino acid accumulation might be attributed to the heat-stable import of amino acids into the caryopsis and/or repression of protein synthesis especially the tRNA charging step under high temperature. An atlas showing the effect of high temperature on levels of metabolites and gene expression in the central metabolic pathways is presented.
- Published
- 2010
16. The potential roles of amino acids and their major derivatives in the management of multiple sclerosis.
- Author
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Pashaei, Somayeh, Yarani, Reza, Mohammadi, Pantea, and Emami Aleagha, Mohammad Sajad
- Subjects
AMINO acid derivatives ,MULTIPLE sclerosis ,LIPID metabolism ,CARBOHYDRATE metabolism ,PHENYLALANINE - Abstract
Recently, we reviewed the important role of carbohydrates and lipids metabolism in different clinical aspects of multiple sclerosis (MS) disease. In the current paper, we aimed to review the contribution of amino acids and their major derivatives to different clinical outcomes of the disease, including etiology, pathogenesis, diagnosis, prognosis, and treatment. In this line, Thr (threonine), Phe (phenylalanine), Glu (glutamate), Trp (tryptophan), and Sero (serotonin) are the main examples of biomolecules that have been suggested for MS therapy. It has been concluded that different amino acids and their derivatives might be considered prominent tools for the clinical management of MS disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
17. Non-targeted GC–MS metabolomics-based differences in Indica rice seeds of different varieties.
- Author
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Zhou, Dahu, Jing, Hao, Yuan, Jun, Zhou, Mingming, Liu, Lin, Fu, Junru, Ouyang, Linjuan, Xu, Jie, Bian, Jianmin, Fu, Haihui, and He, Haohua
- Subjects
RICE seeds ,HUMAN growth ,CARBOHYDRATE metabolism ,GAS chromatography/Mass spectrometry (GC-MS) ,ORGANIC acids ,AMYLOSE - Abstract
Rice seeds of different varieties exhibited distinct metabolic profiles in our study. We analyzed the metabolites in seeds of six rice varieties (CH, HM, NX, YX, HY, and MX) using non-targeted GC–MS. Our findings revealed that amino acids, sugars, and organic acids were predominant in all varieties, with significant differences observed in CH compared to the others. Specifically phenylalanine and glycine content differed notably in NX and YX, respectively. Additionally, 1,5-anhydroglucitol content in NX, and glutamate, aspartate, and lactulose in NX, YX, HM, HY, and MX were up-regulated. Due to the biological functions of these amino acids and sugars, these indicated that compared to CH, rice of NX were more conducive to metabolism of carbohydrate and fat, and healthy growth maintenance in the human body, but mightThese variations suggest that NX rice may be more beneficial for carbohydrate and fat metabolism and overall health maintenance compared to CH. However, it may not be suitable for diabetic patients. YX rice may not be an ideal glycine supplement, rice ofwhile HM, HY, and MX rice could serve as potential lactulose sources. Furthermore, NX and YX rice exhibited higher levels of main storage proteins compared to CH. This study offers valuable insights into the metabolic differences among various rice varieties. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. Inoculation with Lentilactobacillus buchneri alone or in combination with Lentilactobacillus hilgardii modifies gene expression, fermentation profile, and starch digestibility in high-moisture corn.
- Author
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Drouin, Pascal, da Silva, Érica Benjamim, Tremblay, Julien, Chevaux, Eric, Apper, Emmanuelle, and Castex, Mathieu
- Subjects
GENE expression ,AMINO acid metabolism ,STARCH ,CARBOHYDRATE metabolism ,CORN as feed ,GENE expression profiling ,AMINO acids - Abstract
Inoculants combining Lentilactobacillus buchneri and Lentilactobacillus hilgardii have been shown to improve the aerobic stability of high-moisture corn (HMC) and whole-plant corn silage, but the mode of action of this co-inoculation remains to be elucidated. This study used metatranscriptomics to evaluate the effects of inoculation with L. buchneri alone or combined with L. hilgardii on the bacterial community, gene expression, fermentation profile, and starch digestibility in HMC. High-moisture corn not inoculated (Control) or inoculated with L. buchneri NCIMB 40788 (LB) or L. buchneri NCIMB 40788 combined with L. hilgardii CNCM-I-4785 (Combo) was ensiled in mini silo bags for 30, 60, 120, and 180 days. The fermentation profile was evaluated at all time points. Metatranscriptomics was performed on samples collected on day 120. Combo had a greater alpha diversity richness index of contigs than LB and Control, and inoculation with Combo and LB modified the beta-diversity of contigs compared to Control. Out of 69 genes of interest, 20 were differentially expressed in LB compared to Control and 25 in Combo compared to Control. Of those differently expressed genes, 16 (10 of which were associated with carbohydrate metabolism and six with amino acid metabolism) were differently expressed in both LB and Combo compared to Control, and all those genes were upregulated in the inoculated silages. When we compared Combo and LB, we found seven genes expressed differently, four associated with carbohydrate metabolism and downregulated in Combo, and three associated with amino acid metabolism and upregulated in Combo. At day 120, the inoculated silages had more culturable lactic acid bacteria, higher Lactobacillus relative abundance, and lower Leuconostoc relative abundance than Control. The concentration of acetic acid remained low throughout ensiling in Control, but in LB and Combo, it increased up to day 60 and remained stable from day 60 to 180. The 1,2-propanediol was only detected in LB and Combo. Inoculation did not affect the concentration of starch, but starch digestibility was greater in Combo than in Control. Inoculation of HMC with Combo modified the gene expression and fermentation profile compared to Control and LB, improving starch digestibility compared to uninoculated HMC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. Ascorbate and Hydrogen Peroxide Modify Metabolite Profile of Wheat Differently.
- Author
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Asghar, Muhammad Ahsan, Balogh, Eszter, Ahres, Mohamed, Szalai, Gabriella, Gondor, Orsolya Kinga, Darkó, Éva, Borbély, Péter, Kulman, Kitti, Mednyánszky, Zsuzsa, Simon-Sarkadi, Livia, and Kocsy, Gábor
- Subjects
HYDROGEN peroxide ,PENTOSE phosphate pathway ,AMINO acids - Abstract
Effects of ascorbate (ASA) and hydrogen peroxide (H
2 O2 ) on metabolite profile was compared in wheat. Interestingly, the redox environment became more oxidized after ASA treatment and more reduced after H2 O2 addition based on the ratios of oxidised and reduced ascorbate and glutathione. The excess of ASA could inhibit, while H2 O2 could induce the oxidative pentose phosphate pathway producing reducing power as shown by the unchanged and decreased glucose-6-phosphate content, respectively. This different effect on glucose-6-phosphate content can also explain the reduced formation of several amino acids from the intermediate products of glycolysis after ASA treatment and their constant or greater levels after H2 O2 addition. In contrast to most amino acids, the accumulation of Pro was greatly induced by ASA, and this change was fivefold greater than after H2 O2 addition. This difference could also contribute to the distinct redox shifts after the two treatments, since NADPH is oxidised during Pro synthesis. The more oxidising environment after ASA treatment activated several transcripts related to the ascorbate–glutathione cycle and the pentose phosphate pathway. Our results indicate the overcompensating effect of ASA and H2 O2 on the redox environment in leaf tissues and the subsequent different adjustment of metabolite profile and the related transcript levels. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
20. Metabolic Alterations in Canine Mammary Tumors.
- Author
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Tamarindo, Guilherme Henrique, Novais, Adriana Alonso, Chuffa, Luiz Gustavo Almeida, and Zuccari, Debora Aparecida Pires Campos
- Subjects
GLUTAMINE ,GLUTAMINE synthetase ,FATTY acid oxidation ,CARBOHYDRATE metabolism ,FEMALE dogs ,MITOCHONDRIAL DNA ,TUMOR growth - Abstract
Simple Summary: Cancer cells usually have a short timeframe for proliferation, which favors tumor growth. Therefore, they require more energy and intermediates to sustain biosynthetic pathways that will supply all the requirements for cell division. This event is known as metabolic reprogramming and is described in all cancer types, it also being a vulnerability for therapy. However, metabolic alterations in canine mammary tumors are poorly explored. In this review, we compile the metabolic rewiring described in canine mammary tumors, which could be used as a therapeutic opportunity for treatment in veterinary oncology. Canine mammary tumors (CMTs) are among the most common diseases in female dogs and share similarities with human breast cancer, which makes these animals a model for comparative oncology studies. In these tumors, metabolic reprogramming is known as a hallmark of carcinogenesis whereby cells undergo adjustments to meet the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as a therapeutic strategy, which has mostly been tested in human clinical trials but is poorly explored in CMTs. In this dedicated review, we compiled the metabolic changes described for CMTs, emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial functions. We observed key factors associated with the presence and aggressiveness of CMTs, such as an increase in glucose uptake followed by enhanced anaerobic glycolysis via the upregulation of glycolytic enzymes, changes in glutamine catabolism due to the overexpression of glutaminases, increased fatty acid oxidation, and distinct effects depending on lipid saturation, in addition to mitochondrial DNA, which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
21. Transcriptomic profiling revealed important roles of amino acid metabolism in fruiting body formation at different ripening times in Hypsizygus marmoreus.
- Author
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Quanju Xiang, Muhammad Arshad, Yakun Li, Huijuan Zhang, Yunfu Gu, Xiumei Yu, Ke Zhao, Menggen Ma, Lingzi Zhang, Maolan He, and Qiang Chen
- Subjects
FRUITING bodies (Fungi) ,AMINO acid metabolism ,CARBOHYDRATE metabolism ,TRANSCRIPTOMES ,LIPID metabolism ,AMINO acids ,HISTIDINE ,GENE ontology - Abstract
Introduction: Hypsizygus marmoreus is an industrial mushroom that is widely cultivated in East Asia. Its long postripening stage before fruiting severely limits its industrialized production. Methods: Five different mycelial ripening times (30, 50, 70, 90, and 100 d) were chosen and primordia (30P, 50P, 70P, 90P, and 110P) were collected for comparative transcriptomic analyses. The corresponding substrates (30F, 50F, 70F, 90F, and 110F) were used for nutrient content and enzyme activity determination. Results: In pairwise comparisons between 110P and other primordia, a total of 1,194, 977, 773, and 697 differentially expressed genes (DEGs) were identified in 30P_110P, 50P_110P, 70P_110P, and 90P_110P, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) functional enrichment analyses revealed that the DEGs were mainly associated with amino acid metabolism, and lipid and carbohydrate metabolism pathways. Tyrosine, tryptophan, phenylalanine and histidine metabolism were enriched in all groups. Among the main carbon nutrients, the contents of cellulose and hemicellulose were high, and the lignin content decreased with the extension of the ripening time. Laccase had the highest activity, and acid protease activity decreased with the extension of the ripening time. Discussion: The highly enrichment for amino acid metabolic pathways in primordia reveals that these pathways are essential for fruiting body formation in H. marmoreus, and these results will provide a basis for the optimization of its cultivation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
22. Adaptation Strategies to High Hydrostatic Pressures in Pseudothermotoga species Revealed by Transcriptional Analyses.
- Author
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Fenouil, Romain, Pradel, Nathalie, Belahbib, Hassiba, Roumagnac, Marie, Bartoli, Manon, Ben Hania, Wajdi, Denis, Yann, Garel, Marc, Tamburini, Christian, Ollivier, Bernard, Summers, Zarath, Armougom, Fabrice, and Dolla, Alain
- Subjects
HYDROSTATIC pressure ,AMINO acid transport ,AMINO acid metabolism ,PHYSIOLOGICAL adaptation ,CARBOHYDRATE metabolism ,AMINO acids ,GENOMICS - Abstract
Pseudothermotoga elfii strain DSM9442 and P. elfii subsp. lettingae strain DSM14385 are hyperthermophilic bacteria. P. elfii DSM9442 is a piezophile and was isolated from a depth of over 1600 m in an oil-producing well in Africa. P. elfii subsp. lettingae is piezotolerant and was isolated from a thermophilic bioreactor fed with methanol as the sole carbon and energy source. In this study, we analyzed both strains at the genomic and transcriptomic levels, paying particular attention to changes in response to pressure increases. Transcriptomic analyses revealed common traits of adaptation to increasing hydrostatic pressure in both strains, namely, variations in transport membrane or carbohydrate metabolism, as well as species-specific adaptations such as variations in amino acid metabolism and transport for the deep P. elfii DSM9442 strain. Notably, this work highlights the central role played by the amino acid aspartate as a key intermediate of the pressure adaptation mechanisms in the deep strain P. elfii DSM9442. Our comparative genomic and transcriptomic analysis revealed a gene cluster involved in lipid metabolism that is specific to the deep strain and that was differentially expressed at high hydrostatic pressures and might, thus, be a good candidate for a piezophilic gene marker in Pseudothermotogales. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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23. Knockout of Nur77 Leads to Amino Acid, Lipid, and Glucose Metabolism Disorders in Zebrafish.
- Author
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Xu, Yang, Tian, Juanjuan, Kang, Qi, Yuan, Hang, Liu, Chengdong, Li, Zhehui, Liu, Jie, and Li, Mingyu
- Subjects
GLUCOSE metabolism disorders ,WARBURG Effect (Oncology) ,AMINO acids ,CARBOHYDRATE metabolism ,BRACHYDANIO ,LIPID metabolism - Abstract
Orphan nuclear receptor Nur77 has been reported to be implicated in a diverse range of metabolic processes, including carbohydrate metabolism and lipid metabolism. However, the detailed mechanism of Nur77 in the regulation of metabolic pathway still needs to be further investigated. In this study, we created a global nur77 knockout zebrafish model by CRISPR/Cas9 technique, and then performed whole-organism RNA sequencing analysis in wildtype and nur77 -deficient zebrafish to dissect the genetic changes in metabolic-related pathways. We found that many genes involved in amino acid, lipid, and carbohydrate metabolism changed by more than twofold. Furthermore, we revealed that nur77
−/− mutant displayed increased total cholesterol (TC) and triglyceride (TG), alteration in total amino acids, as well as elevated glucose. We also demonstrated that the elevated glucose was not due to the change of glucose uptake but was likely caused by the disorder of glycolysis/gluconeogenesis and the impaired β-cell function, including downregulated insb expression, reduced β-cell mass, and suppressed insulin secretion. Importantly, we also verified that targeted expression of Nur77 in the β cells is sufficient to rescue the β-cell defects in global nur77−/− larvae zebrafish. These results provide new information about the global metabolic network that Nur77 signaling regulates, as well as the role of Nur77 in β-cell function. [ABSTRACT FROM AUTHOR]- Published
- 2022
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24. Fullerenol changes metabolite responses differently depending on the iron status of cucumber plants.
- Author
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Bityutskii, Nikolai P., Yakkonen, Kirill L., Puzanskiy, Roman, Lukina, Kseniia A., Shavarda, Alexey L., and Semenov, Konstantin N.
- Subjects
CUCUMBERS ,AMINO acid metabolism ,CARBOHYDRATE metabolism ,ORGANIC acids ,IRON ions ,IRON ,AMINO acids ,CROP yields - Abstract
The unique properties of carbon-based nanomaterials, including fullerenol, have attracted great interest in agricultural and environmental applications. Iron (Fe) is an essential micronutrient for major metabolic processes, for which a shortage causes chlorosis and reduces the yield of many crops cultivated worldwide. In the current study, the metabolic responses of Cucumis sativus (a Strategy I plant) to fullerenol treatments were investigated depending on the Fe status of plants. Cucumber plants were grown hydroponically, either with [+Fe
II (ferrous) and +FeIII (ferric)] or in Fe-free (−FeII and −FeIII ) nutrient solution, with (+F) or without (−F) a fullerenol supply. Iron species-dependent effects were observed in either Fe-fed or Fe-starved plants, with alteration of metabolites involved in the metabolism of carbohydrates, amino acids, organic acids, lipophilic compounds. Metabolic perturbations triggered by fullerenol in the FeIII -treated plants were in the opposite kind from those in the FeII -treated plants. Whereas in the FeIII -fed plants, fullerenol activated the metabolisation of carbohydrates and amino acids, in the FeII -fed plants, fullerenol activated the metabolisation of lipophilic compounds and repressed the metabolisation of carbohydrates and amino acids. In FeIII -deficient plants, fullerenol stimulated the metabolism of C3 carboxylates and lipophilic compounds while repressing the metabolism of amino acids, hexoses and dicarboxylates, while in FeII -deficient plants, activations of the metabolism of amino acids and dicarboxylates and repression of sterol metabolism by fullerenol were observed. The results indicated that the valence state of Fe sources is of importance for re-programming metabolome responses in cucumber to fullerenol either in Fe-sufficient or Fe-deficient conditions. These investigations are significant for understanding fullerenol interactions and risk assessment in plants with different Fe statuses. [ABSTRACT FROM AUTHOR]- Published
- 2021
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25. Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case--control study.
- Author
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Ciocan, Dragos, Cassard, Anne-Marie, Becquemont, Laurent, Verstuyft, Céline, Sebastian Voican, Cosmin, Asmar, Khalil El, Colle, Romain, David, Denis, Trabado, Séverine, Feve, Bruno, Chanson, Philippe, Perlemuter, Gabriel, and Corruble, Emmanuelle
- Subjects
LIPID metabolism ,TRYPTOPHAN metabolism ,BLOOD microbiology ,MENTAL depression risk factors ,BIOMARKERS ,ANTIDEPRESSANTS ,SEQUENCE analysis ,CARBOHYDRATE metabolism ,METABOLOMICS ,LIQUID chromatography ,GRAM-negative bacteria ,CASE-control method ,METABOLISM ,RISK assessment ,TREATMENT effectiveness ,TRYPTOPHAN ,HUMAN microbiota ,MENTAL depression ,MASS spectrometry ,GRAM-negative aerobic bacteria ,NEISSERIA ,GENOMICS ,AMINO acids ,XENOBIOTICS ,METABOLITES ,BACTERIA ,PHARMACODYNAMICS - Abstract
Background: The microbiota interacts with the brain through the gut--brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment. Methods: In this case--control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry. Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment. Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results. Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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26. The Metabolomics of Chronic Pain Conditions: A Systematic Review.
- Author
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Aroke, Edwin N. and Powell-Roach, Keesha L.
- Subjects
PROTEIN metabolism ,AMINO acids ,CARBOHYDRATE metabolism ,CHRONIC pain ,CINAHL database ,FIBROMYALGIA ,MEDICAL information storage & retrieval systems ,MEDLINE ,METABOLISM ,METABOLITES ,MIGRAINE ,MYALGIA ,ONLINE information services ,OSTEOARTHRITIS ,PAIN management ,SYSTEMATIC reviews ,METABOLOMICS - Abstract
Background: Chronic pain is a significant public health problem in the United States, affecting approximately 100 million people. Yet there is a lack of robust biomarkers for clinical use in chronic pain conditions. Downstream effects of environmental, genomic, and proteomic variations in individuals with chronic pain conditions can be identified and quantified using a metabolomic approach. Aim/Design: The purpose of this systematic review was to examine the literature for reports of potential metabolomic signatures associated with chronic pain conditions. Methods: We searched relevant electronic databases for published studies that used various metabolomic approaches to investigate chronic pain conditions among subjects of all ages. Results: Our search identified a total of 586 articles, 18 of which are included in this review. The reviewed studies used metabolomics to investigate fibromyalgia (n = 5), osteoarthritis (n = 4), migraine (n = 3), musculoskeletal pain (n = 2), and other chronic pain conditions (n = 1/condition). Results show that several known and newly identified metabolites differ in individuals with chronic pain conditions compared to those without these conditions. These include amino acids (e.g., glutamine, serine, and phenylalanine) and intermediate products (e.g., succinate, citrate, acetylcarnitine, and N-acetylornithine) of pathways that metabolize various macromolecules. Conclusion: Though more high-quality research is needed, this review provides insights into potential biomarkers for future metabolomics studies in people with chronic pain conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. A metabolic core model elucidates how enhanced utilization of glucose and glutamine, with enhanced glutamine-dependent lactate production, promotes cancer cell growth
- Author
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Damiani, Chiara, Colombo, Riccardo, Gaglio, Daniela, Mastroianni, Fabrizia, Pescini, Dario, Westerhoff, Hans Victor, Mauri, Giancarlo, Vanoni, Marco, Alberghina, Lilia, Damiani, C, Colombo, R, Gaglio, D, Mastroianni, F, Pescini, D, Westerhoff, H, Mauri, G, Vanoni, M, Alberghina, L, Synthetic Systems Biology (SILS, FNWI), Molecular Cell Physiology, and AIMMS
- Subjects
Metabolic Processes ,0301 basic medicine ,Glucose uptake ,Glutamine ,Biochemistry ,7. Clean energy ,Glucose Metabolism ,Drug Metabolism ,Metabolic Flux Analysi ,Neoplasms ,Metabolic flux analysis ,Medicine and Health Sciences ,Amino Acids ,lcsh:QH301-705.5 ,Ecology ,Organic Compounds ,Acidic Amino Acids ,Monosaccharides ,Ketones ,Enzymes ,Flux balance analysis ,Chemistry ,Computational Theory and Mathematics ,Modeling and Simulation ,Physical Sciences ,Carbohydrate Metabolism ,Oxidoreductases ,Metabolic Networks and Pathways ,Research Article ,Chemical Elements ,Human ,Pyruvate ,Citric Acid Cycle ,Carbohydrates ,Biology ,Models, Biological ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Genetic ,Manchester Institute of Biotechnology ,Genetics ,Animals ,Humans ,Pharmacokinetics ,Computer Simulation ,Lactic Acid ,Molecular Biology ,Dehydrogenases ,Ecology, Evolution, Behavior and Systematics ,Cell Proliferation ,Pharmacology ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Metabolic Networks and Pathway ,Metabolism ,ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology ,Metabolic Flux Analysis ,Oxygen ,Citric acid cycle ,Metabolic pathway ,030104 developmental biology ,Glucose ,lcsh:Biology (General) ,Enzymology ,Acids ,Flux (metabolism) - Abstract
Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism. Sampling of the feasible flux space allowed us to obtain a large number of randomly mutated cells simulated at different glutamine and glucose uptake rates. We observed that, in the limited subset of proliferating cells, most displayed fermentation of glucose to lactate in the presence of oxygen. At high utilization rates of glutamine, oxidative utilization of glucose was decreased, while the production of lactate from glutamine was enhanced. This emergent phenotype was observed only when the available carbon exceeded the amount that could be fully oxidized by the available oxygen. Under the latter conditions, standard Flux Balance Analysis indicated that: this metabolic pattern is optimal to maximize biomass and ATP production; it requires the activity of a branched TCA cycle, in which glutamine-dependent reductive carboxylation cooperates to the production of lipids and proteins; it is sustained by a variety of redox-controlled metabolic reactions. In a K-ras transformed cell line we experimentally assessed glutamine-induced metabolic changes. We validated computational results through an extension of Flux Balance Analysis that allows prediction of metabolite variations. Taken together these findings offer new understanding of the logic of the metabolic reprogramming that underlies cancer cell growth., Author summary Hallmarks describing common key events in initiation, maintenance and progression of cancer have been identified. One hallmark deals with rewiring of metabolic reactions required to sustain enhanced cell proliferation. The availability of molecular, mechanistic models of cancer hallmarks will mightily improve optimized personal treatment and new drug discovery. Metabolism is the only hallmark for which it is currently possible to derive large scale mathematical models, which have predictive ability. In this paper, we exploit a constraint-based model of the core metabolism required for biomass conversion of the most relevant nutrients—glucose and glutamine—to clarify the logic of control of cancer metabolism. We newly report that, when available oxygen is not sufficient to fully oxidize available glucose and glutamine carbons–a situation compatible with that observed under normal oxygen conditions in human and in cancer cells growing in vitro—utilization of glutamine by reductive carboxylation and conversion of glucose and glutamine to lactate confer advantage for biomass production. Redox homeostasis can be maintained through the use of different alternative pathways. In conclusion, this paper offers a logic interpretation to the link between metabolic rewiring and enhanced proliferation, which may offer new approaches to targeted drug discovery and utilization.
- Published
- 2017
28. Metabolite Concentration Changes in Humans After a Bout of Exercise: a Systematic Review of Exercise Metabolomics Studies.
- Author
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Schranner, Daniela, Kastenmüller, Gabi, Schönfelder, Martin, Römisch-Margl, Werner, and Wackerhage, Henning
- Subjects
META-analysis ,METABOLOMICS ,EXERCISE ,ISOMETRIC exercise ,SMALL molecules ,RESISTANCE training ,ONLINE information services ,ENERGY metabolism ,TRICARBOXYLIC acids ,ENDURANCE sports training ,CARBOHYDRATE metabolism ,SYSTEMATIC reviews ,EXERCISE physiology ,NUCLEAR magnetic resonance spectroscopy ,NUCLEOTIDES ,RESEARCH funding ,MASS spectrometry ,MEDLINE ,AMINO acids ,METABOLITES ,PEPTIDES ,LIPIDS - Abstract
Background: Exercise changes the concentrations of many metabolites, which are small molecules (< 1.5 kDa) metabolized by the reactions of human metabolism. In recent years, especially mass spectrometry-based metabolomics methods have allowed researchers to measure up to hundreds of metabolites in a single sample in a non-biased fashion. To summarize human exercise metabolomics studies to date, we conducted a systematic review that reports the results of experiments that found metabolite concentrations changes after a bout of human endurance or resistance exercise. Methods: We carried out a systematic review following PRISMA guidelines and searched for human metabolomics studies that report metabolite concentrations before and within 24 h after endurance or resistance exercise in blood, urine, or sweat. We then displayed metabolites that significantly changed their concentration in at least two experiments. Results: Twenty-seven studies and 57 experiments matched our search criteria and were analyzed. Within these studies, 196 metabolites changed their concentration significantly within 24 h after exercise in at least two experiments. Human biofluids contain mainly unphosphorylated metabolites as the phosphorylation of metabolites such as ATP, glycolytic intermediates, or nucleotides traps these metabolites within cells. Lactate, pyruvate, TCA cycle intermediates, fatty acids, acylcarnitines, and ketone bodies all typically increase after exercise, whereas bile acids decrease. In contrast, the concentrations of proteinogenic and non-proteinogenic amino acids change in different directions. Conclusion: Across different exercise modes and in different subjects, exercise often consistently changes the average concentrations of metabolites that belong to energy metabolism and other branches of metabolism. This dataset is a useful resource for those that wish to study human exercise metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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29. Metabolomic analyses reveal substances that contribute to the increased freezing tolerance of alfalfa (Medicago sativa L.) after continuous water deficit.
- Author
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Xu, Hongyu, Li, Zhenyi, Tong, Zongyong, He, Feng, and Li, Xianglin
- Subjects
ALFALFA ,BETAINE ,UNSATURATED fatty acids ,CARBOHYDRATE metabolism ,OSMOREGULATION ,AMINO acids - Abstract
Background: Alfalfa is a high-quality forage cultivated widely in northern China. Recently, the failure of alfalfa plants to survive the winter has caused substantial economic losses. Water management has attracted considerable attention as a method for the potential improvement of winter survival. The aim of this study was to determine whether and how changes in the water regime affect the freezing tolerance of alfalfa. Results: The alfalfa variety WL353LH was cultivated under water regimes of 80 and 25% of water-holding capacity, and all the plants were subjected to low temperatures at 4/0 °C (light/dark) and then − 2/− 6 °C (light/dark). The semi-lethal temperatures were lower for water-stressed than well-watered alfalfa. The pool sizes of total soluble sugars, total amino acids, and proline changed substantially under water-deficit and low-temperature conditions. Metabolomics analyses revealed 72 subclasses of differential metabolites, among which lipid and lipid-like molecules (e.g., fatty acids, unsaturated fatty acids, and glycerophospholipids) and amino acids, peptides, and analogues (e.g., proline betaine) were upregulated under water-deficit conditions. Some carbohydrates (e.g., D-maltose and raffinose) and flavonoids were also upregulated at low temperatures. Finally, Kyoto Encyclopedia of Genes and Genomes analyses revealed 18 significantly enriched pathways involved in the biosynthesis and metabolism of carbohydrates, unsaturated fatty acids, amino acids, and glycerophospholipids. Conclusions: Water deficit significantly enhanced the alfalfa' freezing tolerance, and this was correlated with increased soluble sugar, amino acid, and lipid and lipid-like molecule contents. These substances are involved in osmotic regulation, cryoprotection, and the synthesis, fluidity, and stability of the cellular membrane. Our study provides a reference for improving alfalfa' winter survival through water management. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Metabolomic profiles in yak mammary gland tissue during the lactation cycle.
- Author
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Li, Zhixiong and Jiang, Mingfeng
- Subjects
MAMMARY glands ,YAK ,LACTATION ,OXALIC acid ,MILKING ,MILK yield - Abstract
The yak is one of the most important domestic animals in Tibetan life for providing basic resources such as milk, meat and transportation. Although yak milk production is not elevated, yak milk is superior to dairy cow milk in nutrient composition (protein and fat). However, the understanding of the metabolic mechanisms of yak mammary gland tissue during the lactation cycle remains elusive. In this study, GC-MS-based metabolomics was employed to study the metabolic variations in the yak mammary gland during the lactation cycle (pregnancy, lactation and dry period). Twenty-nine metabolites were up or downregulated during the lactation period. Compared to the dry period, during the lactation period the levels of oxalic acid were upregulated, while glycine and uridine were downregulated. Thirty-seven pathways were obtained when the 29 differential metabolites were imported into the KEGG pathway analysis. The most impacted pathways during the lactation cycle were glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; TCA cycle; glyoxylate and dicarboxylate metabolism; and pyrimidine metabolism. Our results provide important insights into the metabolic events involved in yak mammary gland development, lactogenesis and lactation, which can guide further research to improve milk yield and enhance the constituents of yak milk. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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31. Metabolic reprogramming dynamics in tumor spheroids: Insights from a multicellular, multiscale model.
- Author
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Roy, Mahua and Finley, Stacey D.
- Subjects
BIOLOGICAL mathematical modeling ,TUMOR growth ,CANCER cell growth ,CANCER cell proliferation ,CANCER prevention - Abstract
Mathematical modeling provides the predictive ability to understand the metabolic reprogramming and complex pathways that mediate cancer cells’ proliferation. We present a mathematical model using a multiscale, multicellular approach to simulate avascular tumor growth, applied to pancreatic cancer. The model spans three distinct spatial and temporal scales. At the extracellular level, reaction diffusion equations describe nutrient concentrations over a span of seconds. At the cellular level, a lattice-based energy driven stochastic approach describes cellular phenomena including adhesion, proliferation, viability and cell state transitions, occurring on the timescale of hours. At the sub-cellular level, we incorporate a detailed kinetic model of intracellular metabolite dynamics on the timescale of minutes, which enables the cells to uptake and excrete metabolites and use the metabolites to generate energy and building blocks for cell growth. This is a particularly novel aspect of the model. Certain defined criteria for the concentrations of intracellular metabolites lead to cancer cell growth, proliferation or death. Overall, we model the evolution of the tumor in both time and space. Starting with a cluster of tumor cells, the model produces an avascular tumor that quantitatively and qualitatively mimics experimental measurements of multicellular tumor spheroids. Through our model simulations, we can investigate the response of individual intracellular species under a metabolic perturbation and investigate how that response contributes to the response of the tumor as a whole. The predicted response of intracellular metabolites under various targeted strategies are difficult to resolve with experimental techniques. Thus, the model can give novel predictions as to the response of the tumor as a whole, identifies potential therapies to impede tumor growth, and predicts the effects of those therapeutic strategies. In particular, the model provides quantitative insight into the dynamic reprogramming of tumor cells at the intracellular level in response to specific metabolic perturbations. Overall, the model is a useful framework to study targeted metabolic strategies for inhibiting tumor growth. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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32. Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation.
- Author
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Rabin-Court, Aviva, Rodrigues, Marcos R., Zhang, Xian-Man, and Perry, Rachel J.
- Subjects
OXIDATION of glucose ,SMALL cell lung cancer ,INSULIN ,CITRATE synthase ,ANAPLASTIC lymphoma kinase ,CELL division - Abstract
Obesity is associated with increased incidence and worse prognosis of more than one dozen tumor types; however, the molecular mechanisms for this association remain under debate. We hypothesized that insulin, which is elevated in obesity-driven insulin resistance, would increase tumor glucose oxidation in obesity-associated tumors. To test this hypothesis, we applied and validated a stable isotope method to measure the ratio of pyruvate dehydrogenase flux to citrate synthase flux (V
PDH /VCS , i.e. the percent of total mitochondrial oxidation fueled by glucose) in tumor cells. Using this method, we found that three tumor cell lines associated with obesity (colon cancer [MC38], breast cancer [4T1], and prostate cancer [TRAMP-C3] cells) increase VPDH /VCS in response to physiologic concentrations of insulin. In contrast, three tumor cell lines that are not associated with obesity (melanoma [YUMM1.7], B cell lymphoma [BCL1 clone 5B1b], and small cell lung cancer [NCI-H69] cells) exhibited no oxidative response to insulin. The observed increase in glucose oxidation in response to insulin correlated with a dose-dependent increase in cell division in obesity-associated tumor cell lines when grown in insulin, whereas no alteration in cell division was seen in tumor types not associated with obesity. These data reveal that a shift in substrate preference in the setting of physiologic insulin may comprise a metabolic signature of obesity-associated tumors that differs from that of those not associated with obesity. [ABSTRACT FROM AUTHOR]- Published
- 2019
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33. NMR-based metabolic profiling of urine, serum, fecal, and pancreatic tissue samples from the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer.
- Author
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Schmahl, Michelle J., Regan, Daniel P., Rivers, Adam C., Joesten, William C., and Kennedy, Michael A.
- Subjects
PANCREATIC cancer ,NUCLEAR magnetic resonance spectroscopy ,LABORATORY mice ,CANCER-related mortality ,TUMOR markers - Abstract
Pancreatic cancer is the third leading cause of cancer deaths in the United States with more than 53,000 expected to be diagnosed with the disease in 2018. The median survival time after diagnosis is four to six months. The poor survival statistics are due in part to the fact that pancreatic cancer is typically asymptomatic until it reaches advanced stages of the disease. Although surgical resection provides the best chance of survival, pancreatic cancer is rarely detected when surgery is still possible due, in part, to lack of effective biomarkers for early detection. The goal of the research reported here was to determine if it was possible to identify metabolic biomarkers for detection of pre-cancerous pancreatic intraepithelial neoplasia (PanIN) that precede pancreatic adenocarcinoma. The transgenic Ptf1a-Cre; LSL-KrasG12D mouse strain was used as a model of pancreatic cancer progression. Nuclear magnetic resonance (NMR) spectroscopy was employed to compare metabolic profiles of urine, sera, fecal extracts, and pancreatic tissue extracts collected from control and study mice aged 5, 11, and 15 months, including 47 mice with tumors. We were able to identify the following potential biomarkers: decreased 3-indoxylsulfate, benzoate and citrate in urine, decreased glucose, choline, and lactate in blood, and decreased phenylalanine and benzoate and increased acetoin in fecal extracts. Potential biomarkers were validated by p-values, PLS-DA VIP scores, and accuracies based on area under ROC curve analyses. Essentially, all of the metabolic profiling changes could be explained as being associated with the consequences of bicarbonate wasting caused by a complete substitution of the normal pancreatic acinar tissue by tissue entirely composed of PanIN. Given the nature of the mouse model used here, our results indicate that it may be possible to use NMR-based metabolic profiling to identify biomarkers for detection of precancerous PanIN that immediately precede pancreatic cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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34. Lens metabolomic profiling as a tool to understand cataractogenesis in Atlantic salmon and rainbow trout reared at optimum and high temperature.
- Author
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Remø, Sofie Charlotte, Hevrøy, Ernst Morten, Breck, Olav, Olsvik, Pål Asgeir, and Waagbø, Rune
- Subjects
METABOLOMICS ,SYSTEMS biology ,RAINBOW trout ,ONCORHYNCHUS ,ATLANTIC salmon - Abstract
Periods of high or fluctuating seawater temperatures result in several physiological challenges for farmed salmonids, including an increased prevalence and severity of cataracts. The aim of the present study was to compare cataractogenesis in Atlantic salmon (Salmo salar L.) and rainbow trout (Oncorhynchus mykiss) reared at two temperatures, and investigate whether temperature influences lens metabolism and cataract development. Atlantic salmon (101±2 g) and rainbow trout (125±3 g) were reared in seawater at either 13°C (optimum for growth) or 19°C during the 35 days experiment (n = 4 tanks for each treatment). At the end of the experiment, the prevalence of cataracts was nearly 100% for Atlantic salmon compared to ~50% for rainbow trout, irrespective of temperature. The severity of the cataracts, as evaluated by slit-lamp inspection of the lens, was almost three fold higher in Atlantic salmon compared to rainbow trout. The global metabolic profile revealed differences in lens composition and metabolism between the two species, which may explain the observed differences in cataract susceptibility between the species. The largest differences were seen in the metabolism of amino acids, especially the histidine metabolism, and this was confirmed by a separate quantitative analysis. The global metabolic profile showed temperature dependent differences in the lens carbohydrate metabolism, osmoregulation and redox homeostasis. The results from the present study give new insight in cataractogenesis in Atlantic salmon and rainbow trout reared at high temperature, in addition to identifying metabolic markers for cataract development. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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35. Mated Drosophila melanogaster females consume more amino acids during the dark phase.
- Author
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Uchizono, Shun, Tabuki, Yumi, Kawaguchi, Natsumi, Tanimura, Teiichi, and Itoh, Taichi Q.
- Subjects
HOMEOSTASIS ,DROSOPHILA melanogaster ,AMINO acid deficiency ,AMINO acids ,CIRCADIAN rhythms - Abstract
To maintain homeostasis, animals must ingest appropriate quantities, determined by their internal nutritional state, of suitable nutrients. In the fruit fly Drosophila melanogaster, an amino acid deficit induces a specific appetite for amino acids and thus results in their increased consumption. Although multiple processes of physiology, metabolism, and behavior are under circadian control in many organisms, it is unclear whether the circadian clock also modulates such motivated behavior driven by an internal need. Differences in levels of amino acid consumption by flies between the light and dark phases of the day:night cycle were examined using a capillary feeder assay following amino acid deprivation. Female flies exhibited increased consumption of amino acids during the dark phase compared with the light phase. Investigation of mutants lacking a functional period gene (per
0 ), a well-characterized clock gene in Drosophila, found no difference between the light and dark phases in amino acid consumption by per0 flies. Furthermore, increased consumption of amino acids during the dark phase was observed in mated but not in virgin females, which strongly suggested that mating is involved in the rhythmic modulation of amino acid intake. Egg production, which is induced by mating, did not affect the rhythmic change in amino acid consumption, although egg-laying behavior showed a per0 -dependent change in rhythm. Elevated consumption of amino acids during the dark phase was partly induced by the action of a seminal protein, sex peptide (SP), on the sex peptide receptor (SPR) in females. Moreover, we showed that the increased consumption of amino acids during the dark phase is induced in mated females independently of their internal level of amino acids. These results suggest that a post-mating SP/SPR signal elevates amino acid consumption during the dark phase via the circadian clock. [ABSTRACT FROM AUTHOR]- Published
- 2017
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36. Aligning Metabolic Pathways Exploiting Binary Relation of Reactions.
- Author
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Huang, Yiran, Zhong, Cheng, Lin, Hai Xiang, and Huang, Jing
- Subjects
AMINO acid metabolism ,SUBGRAPHS ,MULTIPLICATION ,SEQUENCE alignment ,MATHEMATICAL mappings ,BIOCHEMICAL research - Abstract
Metabolic pathway alignment has been widely used to find one-to-one and/or one-to-many reaction mappings to identify the alternative pathways that have similar functions through different sets of reactions, which has important applications in reconstructing phylogeny and understanding metabolic functions. The existing alignment methods exhaustively search reaction sets, which may become infeasible for large pathways. To address this problem, we present an effective alignment method for accurately extracting reaction mappings between two metabolic pathways. We show that connected relation between reactions can be formalized as binary relation of reactions in metabolic pathways, and the multiplications of zero-one matrices for binary relations of reactions can be accomplished in finite steps. By utilizing the multiplications of zero-one matrices for binary relation of reactions, we efficiently obtain reaction sets in a small number of steps without exhaustive search, and accurately uncover biologically relevant reaction mappings. Furthermore, we introduce a measure of topological similarity of nodes (reactions) by comparing the structural similarity of the k-neighborhood subgraphs of the nodes in aligning metabolic pathways. We employ this similarity metric to improve the accuracy of the alignments. The experimental results on the KEGG database show that when compared with other state-of-the-art methods, in most cases, our method obtains better performance in the node correctness and edge correctness, and the number of the edges of the largest common connected subgraph for one-to-one reaction mappings, and the number of correct one-to-many reaction mappings. Our method is scalable in finding more reaction mappings with better biological relevance in large metabolic pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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37. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.
- Author
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Martinelli, Federico, Dolan, David, Fileccia, Veronica, Reagan, Russell L., Phu, My, Spann, Timothy M., McCollum, Thomas G., and Dandekar, Abhaya M.
- Subjects
CITRUS greening disease ,EARLY diagnosis ,PLANT molecular biology ,ADENINE ,INSECTS as carriers of disease - Abstract
Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
38. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide.
- Author
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Ippolito, Joseph E., Brandenburg, Matthew W., Ge, Xia, Crowley, Jan R., Kirmess, Kristopher M., Som, Avik, D’Avignon, D. Andre, Arbeit, Jeffrey M., Achilefu, Samuel, Yarasheski, Kevin E., and Milbrandt, Jeffrey
- Subjects
NEUROENDOCRINOLOGY ,PROSTATE cancer ,CANCER cells ,METABOLISM ,HYPOXEMIA ,DRUG efficacy - Abstract
Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
39. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology.
- Author
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Oliveira, Matheus P., Correa Soares, Juliana B. R., and Oliveira, Marcus F.
- Subjects
SCHISTOSOMA mansoni ,SCHISTOSOMIASIS ,OXYGEN consumption ,REACTIVE oxygen species ,CANCER chemotherapy - Abstract
Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute to redox biology among parasite sexes. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
40. Post-Bariatric Surgery Changes in Quinolinic and Xanthurenic Acid Concentrations Are Associated with Glucose Homeostasis.
- Author
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Favennec, Marie, Hennart, Benjamin, Verbanck, Marie, Pigeyre, Marie, Caiazzo, Robert, Raverdy, Violeta, Verkindt, Hélène, Leloire, Audrey, Guillemin, Gilles J., Yengo, Loïc, Allorge, Delphine, Froguel, Philippe, Pattou, François, and Poulain-Godefroy, Odile
- Subjects
BARIATRIC surgery ,QUINOLINE ,PHYSIOLOGICAL effects of glucose ,BIOACTIVE compounds ,TRYPTOPHAN ,HOMEOSTASIS - Abstract
Background: An increase of plasma kynurenine concentrations, potentially bioactive metabolites of tryptophan, was found in subjects with obesity, resulting from low-grade inflammation of the white adipose tissue. Bariatric surgery decreases low-grade inflammation associated with obesity and improves glucose control. Objective: Our goal was to determine the concentrations of all kynurenine metabolites after bariatric surgery and whether they were correlated with glucose control improvement. Design: Kynurenine metabolite concentrations, analysed by liquid or gas chromatography coupled with tandem mass spectrometry, circulating inflammatory markers, metabolic traits, and BMI were measured before and one year after bariatric surgery in 44 normoglycemic and 47 diabetic women with obesity. Associations between changes in kynurenine metabolites concentrations and in glucose control and metabolic traits were analysed between baseline and twelve months after surgery. Results: Tryptophan and kynurenine metabolite concentrations were significantly decreased one year after bariatric surgery and were correlated with the decrease of the usCRP in both groups. Among all the kynurenine metabolites evaluated, only quinolinic acid and xanthurenic acid were significantly associated with glucose control improvement. The one year delta of quinolinic acid concentrations was negatively associated with the delta of fasting glucose (p = 0.019) and HbA1c (p = 0.014), whereas the delta of xanthurenic acid was positively associated with the delta of insulin sensitivity index (p = 0.0018). Conclusion: Bariatric surgery has induced a global down-regulation of kynurenine metabolites, associated with weight loss. Our results suggest that, since kynurenine monoxygenase diverts the kynurenine pathway toward the synthesis of xanthurenic acid, its inhibition may also contribute to glucose homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
41. Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors.
- Author
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Barollo, Susi, Bertazza, Loris, Watutantrige-Fernando, Sara, Censi, Simona, Cavedon, Elisabetta, Galuppini, Francesca, Pennelli, Gianmaria, Fassina, Ambrogio, Citton, Marilisa, Rubin, Beatrice, Pezzani, Raffaele, Benna, Clara, Opocher, Giuseppe, Iacobone, Maurizio, and Mian, Caterina
- Subjects
PHEOCHROMOCYTOMA ,AMINO acids ,NEUROENDOCRINE tumors ,GENETIC overexpression ,POLYMERASE chain reaction ,GENETICS ,DIAGNOSIS ,THERAPEUTICS - Abstract
Background: 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (
18 F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC).18 F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC. Methods: Real-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization. Results: LAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization. Conclusions: The present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
42. Contribution of Drosophila TRPA1 to Metabolism.
- Author
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Lee, Jung-Eun, Kim, Yunjung, Kim, Kyoung Heon, Lee, Do Yup, and Lee, Youngseok
- Subjects
TRP channels ,DROSOPHILA ,INSECT metabolism ,PROTEIN expression ,SOMATOMEDIN - Abstract
Transient receptor potential (TRP) cation channels are highly conserved in humans and insects. Some of these channels are expressed in internal organs and their functions remain incompletely understood. By direct knock-in of the GAL4 gene into the trpA1 locus in Drosophila, we identified the expression of this gene in the subesophageal ganglion (SOGs) region. In addition, the neurites present in the dorsal posterior region as well as the drosophila insulin-like peptide 2 (dILP2)-positive neurons send signals to the SOGs. The signal is sent to the crop, which is an enlarged organ of the esophagus and functions as a storage place for food in the digestive system. To systematically investigate the role of TRPA1 in metabolism, we applied non-targeted metabolite profiling analysis together with gas-chromatography/time-of-flight mass spectrometry, with an aim to identify a wide range of primary metabolites. We effectively captured distinctive metabolomic phenotypes and identified specific metabolic dysregulation triggered by TRPA1 mutation based on reconstructed metabolic network analysis. Primarily, the network analysis pinpointed the simultaneous down-regulation of intermediates in the methionine salvation pathway, in contrast to the synchronized up-regulation of a range of free fatty acids. The gene dosage-dependent dynamics of metabolite levels among wild-type, hetero- and homozygous mutants, and their coordinated metabolic modulation under multiple gene settings across five different genotypes confirmed the direct linkages of TRPA1 to metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
43. Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.
- Author
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Palorini, Roberta, Votta, Giuseppina, Pirola, Yuri, De Vitto, Humberto, De Palma, Sara, Airoldi, Cristina, Vasso, Michele, Ricciardiello, Francesca, Lombardi, Pietro Paolo, Cirulli, Claudia, Rizzi, Raffaella, Nicotra, Francesco, Hiller, Karsten, Gelfi, Cecilia, Alberghina, Lilia, and Chiaradonna, Ferdinando
- Subjects
CYCLIC-AMP-dependent protein kinase genetics ,CANCER cells ,CELLULAR immunity ,CELL metabolism ,GLYCOLYSIS ,ANOIKIS - Abstract
Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA) axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER) stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
44. Burkholderia pseudomallei Colony Morphotypes Show a Synchronized Metabolic Pattern after Acute Infection.
- Author
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Gierok, Philipp, Kohler, Christian, Steinmetz, Ivo, and Lalk, Michael
- Subjects
BURKHOLDERIA pseudomallei ,SOIL microbiology ,OXIDATIVE stress ,AMINO acids ,METABOLITES ,DNA replication - Abstract
Background: Burkholderia pseudomallei is a water and soil bacterium and the causative agent of melioidosis. A characteristic feature of this bacterium is the formation of different colony morphologies which can be isolated from environmental samples as well as from clinical samples, but can also be induced in vitro. Previous studies indicate that morphotypes can differ in a number of characteristics such as resistance to oxidative stress, cellular adhesion and intracellular replication. Yet the metabolic features of B. pseudomallei and its different morphotypes have not been examined in detail so far. Therefore, this study aimed to characterize the exometabolome of B. pseudomallei morphotypes and the impact of acute infection on their metabolic characteristics. Methods and Principal Findings: We applied nuclear magnetic resonance spectroscopy (
1 H-NMR) in a metabolic footprint approach to compare nutrition uptake and metabolite secretion of starvation induced morphotypes of the B. pseudomallei strains K96243 and E8. We observed gluconate production and uptake in all morphotype cultures. Our study also revealed that among all morphotypes amino acids could be classified with regard to their fast and slow consumption. In addition to these shared metabolic features, the morphotypes varied highly in amino acid uptake profiles, secretion of branched chain amino acid metabolites and carbon utilization. After intracellular passage in vitro or murine acute infection in vivo, we observed a switch of the various morphotypes towards a single morphotype and a synchronization of nutrient uptake and metabolite secretion. Conclusion: To our knowledge, this study provides first insights into the basic metabolism of B. pseudomallei and its colony morphotypes. Furthermore, our data suggest, that acute infection leads to the synchronization of B. pseudomallei colony morphology and metabolism through yet unknown host signals and bacterial mechanisms. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
45. Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.
- Author
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Rafikova, Olga, Meadows, Mary L., Kinchen, Jason M., Mohney, Robert P., Maltepe, Emin, Desai, Ankit A., Yuan, Jason X.-J., Garcia, Joe G. N., Fineman, Jeffrey R., Rafikov, Ruslan, and Black, Stephen M.
- Subjects
PULMONARY hypertension diagnosis ,METABOLIC profile tests ,MONOCROTALINE ,LABORATORY rats ,DISEASE progression - Abstract
There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
46. 13C-Breath testing in animals: theory, applications, and future directions
- Author
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McCue, Marshall D. and Welch, Jr., Kenneth C.
- Published
- 2016
- Full Text
- View/download PDF
47. The Role of the Carbohydrate Recognition Domain of Placental Protein 13 (PP13) in Pregnancy Evaluated with Recombinant PP13 and the DelT221 PP13 Variant.
- Author
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Sammar, Marei, Nisamblatt, Shahar, Gonen, Ron, Huppertz, Berthold, Gizurarson, Sveinbjorn, Osol, George, and Meiri, Hamutal
- Subjects
PREGNANCY proteins ,PREGNANCY complications ,RECOMBINANT proteins ,CARBOHYDRATE metabolism ,PREECLAMPSIA ,AMINO acids - Abstract
Introduction: Placental protein 13 (PP13), a placenta specific protein, is reduced in the first trimester of pregnancy in women who subsequently develop preeclampsia. A naturally occurring PP13 deletion of thymidine at position 221 (DelT
221 or truncated variant) is associated with increased frequency of severe preeclampsia. In this study we compared the full length (wildtype) PP13 and the truncated variant. Methods: Full length PP13 or its DelT221 variant were cloned, expressed and purified from E-Coli. Both variants were administrated into pregnant rats at day 8 of pregnancy for slow release (>5 days) through osmotic pumps and rat blood pressure was measured. Animals were sacrificed at day 15 or day 21 and their utero-placental vasculature was examined. Results: The DelT221 variant (11 kDA) lacked exon 4 and a part of exon 3, and is short of 2 amino acids involved in the carbohydrate (CRD) binding of the wildtype (18 kDA). Unlike the wildtype PP13, purification of DelT221 variant required special refolding. PP13 specific poly- clonal antibodies recognized both PP13 and DelT221 but PP13 specific monoclonal antibodies recognized only the wildtype, indicating the loss of major epitopes. Wildtype PP13 mRNA and its respective proteins were both lower in PE patients compared to normal pregnancies. The DelT221 mutant was not found in a large Caucasian cohort. Pregnant rats exposed to wildtype or DelT221 PP13 variants had significantly lower blood pressure compared to control. The wildtype but not the DelT221 mutant caused extensive vein expansion. Conclusion: This study revealed the importance of PP13 in regulating blood pressure and expanding the utero-placental vasculature in pregnant rats. PP13 mutant lacking amino acids of the PP13 CRD domain fails to cause vein expansion but did reduce blood pressure. The study provides a basis for replenishing patients at risk for preeclampsia by the full length but not the truncated PP13. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
48. HIF1α and HIF2α Exert Distinct Nutrient Preferences in Renal Cells.
- Author
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Arreola, Alexandra, Cowey, C. Lance, Coloff, Jonathan L., Rathmell, Jeffrey C., and Rathmell, W. Kimryn
- Subjects
HYPOXIA-inducible factors ,RENAL cell carcinoma ,CANCER cell growth ,CELL metabolism ,TRANSCRIPTION factors ,GENE expression ,GLYCOLYSIS - Abstract
Background: Hypoxia Inducible Factors (HIF1α and HIF2α) are commonly stabilized and play key roles related to cell growth and metabolic programming in clear cell renal cell carcinoma. The relationship of these factors to discretely alter cell metabolic activities has largely been described in cancer cells, or in hypoxic conditions, where other confounding factors undoubtedly compete. These transcription factors and their specific roles in promoting cancer metabolic phenotypes from the earliest stages are poorly understood in pre-malignant cells. Methods: We undertook an analysis of SV40-transformed primary kidney epithelial cells derived from newborn mice genetically engineered to express a stabilized HIF1α or HIF2α transgene. We examined the metabolic profile in relation to each gene. Results: Although the cells proliferated similarly, the metabolic profile of each genotype of cell was markedly different and correlated with altered gene expression of factors influencing components of metabolic signaling. HIF1α promoted high levels of glycolysis as well as increased oxidative phosphorylation in complete media, but oxidative phosphorylation was suppressed when supplied with single carbon source media. HIF2α, in contrast, supported oxidative phosphorylation in complete media or single glucose carbon source, but these cells were not responsive to glutamine nutrient sources. This finding correlates to HIF2α-specific induction of Glul, effectively reducing glutamine utilization by limiting the glutamate pool, and knockdown of Glul allows these cells to perform oxidative phosphorylation in glutamine media. Conclusion: HIF1α and HIF2α support highly divergent patterns of kidney epithelial cell metabolic phenotype. Expression of these factors ultimately alters the nutrient resource utilization and energy generation strategy in the setting of complete or limiting nutrients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
49. Effects of exogenous l-arginine on in vitro rooting, chlorophyll, carbohydrate, and proline concentrations in the sweet cherry rootstock M × M 14 ( Prunus avium L. × Prunus mahaleb L.).
- Author
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Sarropoulou, Virginia, Dimassi-Theriou, Kortessa, and Therios, Ioannis
- Subjects
PHOTOSYNTHETIC pigments ,CHLOROPLAST pigments ,PLANT shoots ,PROLINE ,CARBOHYDRATE synthesis ,CARBOHYDRATE metabolism - Abstract
The effects of indole-3-butyric acid (IBA) alone and in combination with l-arginine on the morphogenic and biochemical responses in shoot tip explants of the cherry rootstock M × M 14 ( Prunus avium × Prunus mahaleb) were examined. The maximum root number per rooted explant (16), root fresh (FW) and dry (DW) weights, as well as the rooting percentage (100 %) were recorded when 2 mg l IBA (alone) were applied. Including the lowest IBA concentration (0.5 mg l) with the lowest and highest l-arginine concentrations (0.5 and 2 mg l, respectively) resulted in the greatest root length. The maximum leaf chlorophyll concentration and shoot length of the initial explant were recorded when 0.5 mg l IBA plus 2 mg l l-arginine were applied. In addition, l-arginine in combination with IBA (1 and 2 mg l) was found to suppress shoot FW and DW. On the other hand, l-arginine enhanced the promoting effect of IBA on both root length and leaf chlorophyll concentration. The carbohydrate and proline concentrations in leaves were not significantly altered with the application of IBA alone or in combination with l-arginine. On the other hand, the carbohydrate and proline concentrations in roots were decreased with the application of 1 and 2 mg l IBA with l-arginine, resulting in the suppression of the promoting effects of IBA. It is clear from the findings that l-arginine has a direct effect on the in vitro rooting of M × M 14 explants, is involved in the function of the photosythetic apparatus, influences leaf chlorophyll content, participates in carbohydrate biosynthesis and metabolism, and is involved in proline accumulation both in leaves and roots. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
50. A Simple Approach for COnsumption and RElease (CORE) Analysis of Metabolic Activity in Single Mammalian Embryos.
- Author
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Guerif, Fabrice, McKeegan, Paul, Leese, Henry J., and Sturmey, Roger G.
- Subjects
BIOTRANSFORMATION (Metabolism) ,MAMMAL embryology ,BIOLOGICAL assay ,FERTILIZATION in vitro ,LACTATES ,PYRUVATES ,HIGH performance liquid chromatography - Abstract
Non-invasive assay of the consumption and release of metabolites by individual human embryos could allow selection at the cleavage stage of development and facilitate Single Embryo Transfer in clinical IVF but will require simple, high throughput, sensitive methods applicable to small volume samples. A rapid, simple, non-invasive method has therefore been devised using a standard fluorescence plate reader, and used to measure the consumption of pyruvate and glucose, and release of lactate by single bovine embryos at all stages of preimplantation development in culture; amino acid profiles have been determined using HPLC. Early embryos with an ‘intermediate’ level (6.14±0.27 pmol/embryo/h) of pyruvate uptake were associated with the highest rate (68.3%) of blastocyst development indicating that a mid “optimum” range of pyruvate consumption correlates with high viability in this bovine model. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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