PubMed

Related Articles Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts. J Magn Reson. 2019 Jun 04;305:41-50 Authors: Jannin S, Dumez JN, Giraudeau P, Kurzbach D Abstract Dissolution dynamic nuclear polarization (d-DNP) is a versatile method to enhance nuclear magnetic resonance (NMR) spectroscopy. It boosts signal intensities by four to five orders of magnitude thereby providing the potential to improve and enable a plethora of applications ranging from the real-time monitoring of chemical or biological processes to metabolomics and in-cell investigations. This perspectives article highlights possible avenues for developments and applications of d-DNP in biochemical and physicochemical studies. It outlines how chemists, biologists and physicists with various fields of interest can transform and employ d-DNP as a powerful characterization method for their research. PMID: 31203098 [PubMed - as supplied by publisher]

Related Articles Characterizing the Steroidal Milieu in Amniotic Fluid of Mid-Gestation: A GC-MS Study. J Steroid Biochem Mol Biol. 2019 Jun 13;:105412 Authors: Wang R, Hartmann MF, Tiosano D, Wudy SA Abstract Intact steroid hormone biosynthesis is essential for growth and development of the human fetus and embryo. In the present study, gas chromatography-mass spectrometry was employed to characterize the steroidal milieu in amniotic fluid (n = 65; male: female = 35: 30) of mid-gestation (median: 18.8th week, range: 16.0th - 24.6th week) by a comprehensive targeted steroid hormone metabolomics approach. The levels of 52 steroids including pregnenolone and 17-OH-pregnenolone metabolites, dehydroepiandrosterone (DHEA) and its metabolites, progesterone and 17-OH-progesterone metabolites, sex hormones as well as corticosterone and cortisol metabolites were measured. The dominating steroids were the group of pregnenolone and 17-OH-pregnenolone metabolites (mean ± SD: 138.0 ± 59.3 ng/mL), followed by the group of progesterone and 17-OH-progesterone metabolites (107.3 ± 44.3 ng/mL), and thereafter DHEA and its metabolites (97.1 ± 56.5 ng/mL). With respect to sex steroids, only testosterone showed a significantly higher value in male fetuses (p < 0.0001). Of all estrogen metabolites, estriol showed by far the highest concentrations (33.2 ± 26.1 ng/mL). Interestingly, cortisol metabolites were clearly present (59.6 ± 13.6 ng/mL) though fetal de novo synthesis of cortisol is assumed to start from gestational 28th week onwards. Our comprehensive characterization of the steroidal milieu in amniotic fluid of mid-gestation shows presence of all relevant classes of steroid hormones and provides reference data. We conclude that the steroidal milieu in amniotic fluid mirrors the steroidome of the feto-placental unit. PMID: 31202857 [PubMed - as supplied by publisher]

Related Articles Discovery and validation of temporal patterns involved in human brain ketometabolism in cerebral microdialysis fluids of traumatic brain injury patients. EBioMedicine. 2019 Jun 12;: Authors: Eiden M, Christinat N, Chakrabarti A, Sonnay S, Miroz JP, Cuenoud B, Oddo M, Masoodi M Abstract BACKGROUND: Traumatic brain injury (TBI) is recognized as a metabolic disease, characterized by acute cerebral glucose hypo-metabolism. Adaptive metabolic responses to TBI involve the utilization of alternative energy substrates, such as ketone bodies. Cerebral microdialysis (CMD) has evolved as an accurate technique allowing continuous sampling of brain extracellular fluid and assessment of regional cerebral metabolism. We present the successful application of a combined hypothesis- and data-driven metabolomics approach using repeated CMD sampling obtained routinely at patient bedside. Investigating two patient cohorts (n = 26 and n = 12), we identified clinically relevant metabolic patterns at the acute post-TBI critical care phase. METHODS: Clinical and CMD metabolomics data were integrated and analysed using in silico and data modelling approaches. We used both unsupervised and supervised multivariate analysis techniques to investigate structures within the time series and associations with patient outcome. FINDINGS: The multivariate metabolite time series exhibited two characteristic brain metabolic states that were attributed to changes in key metabolites: valine, 4-methyl-2-oxovaleric acid (4-MOV), isobeta-hydroxybutyrate (iso-bHB), tyrosyine, and 2-ketoisovaleric acid (2-KIV). These identified cerebral metabolic states differed significantly with respect to standard clinical values. We validated our findings in a second cohort using a classification model trained on the cerebral metabolic states. We demonstrated that short-term (therapeutic intensity level (TIL)) and mid-term patient outcome (6-month Glasgow Outcome Score (GOS)) can be predicted from the time series characteristics. INTERPRETATION: We identified two specific cerebral metabolic patterns that are closely linked to ketometabolism and were associated with both TIL and GOS. Our findings support the view that advanced metabolomics approaches combined with CMD may be applied in real-time to predict short-term treatment intensity and long-term patient outcome. PMID: 31202815 [PubMed - as supplied by publisher]

Related Articles Influence of cell-cell contact between L. thermotolerans and S. cerevisiae on yeast interactions and the exo-metabolome. Food Microbiol. 2019 Oct;83:122-133 Authors: Petitgonnet C, Klein GL, Roullier-Gall C, Schmitt-Kopplin P, Quintanilla-Casas B, Vichi S, Julien-David D, Alexandre H Abstract Sequential fermentation of grape must inoculated with L. thermotolerans and then S. cerevisiae 24 h later (typical wine-making practice) was conducted with or without cell-cell contact between the two yeast species. We monitored cell viability of the two species throughout fermentation by flow cytometry. The cell viability of S. cerevisiae decreased under both conditions, but the decrease was greater if there was cell-cell contact. An investigation of the nature of the interactions showed competition between the two species for nitrogen compounds, oxygen, and must sterols. Volatile-compound analysis showed differences between sequential and pure fermentation and that cell-cell contact modifies yeast metabolism, as the volatile-compound profile was significantly different from that of sequential fermentation without cell-cell contact. We further confirmed that cell-cell contact modifies yeast metabolism by analyzing the exo-metabolome of all fermentations by FT-ICR-MS analysis. These analyses show specific metabolite production and quantitative metabolite changes associated with each fermentation condition. This study shows that cell-cell contact not only affects cell viability, as already reported, but markedly affects yeast metabolism. PMID: 31202403 [PubMed - in process]

Related Articles Application of UHPLC-Q/TOF-MS-based metabolomics in the evaluation of metabolites and taste quality of Chinese fish sauce (Yu-lu) during fermentation. Food Chem. 2019 Oct 30;296:132-141 Authors: Wang Y, Li C, Li L, Yang X, Chen S, Wu Y, Zhao Y, Wang J, Wei Y, Yang D Abstract Spontaneous fermentation is a critical step in the processing of high-quality fish sauce. In this study, a comparative UHPLC-Q/TOF-MS-based metabolomics approach combining equivalent-quantification and the taste activity value (TAV) was used, for the first time, to evaluate the taste qualities and characterize metabolite profiles in Chinese fish sauce during fermentation. A total of 22,816 metabolite ion features were extracted from fish sauce samples. Forty-six metabolites, including amino acids, small peptides, organic acids, amines, carbohydrates, and nucleic acids, were identified as key chemical components of fish sauce. In addition, absolute quantification and TAV showed that aspartic acid and glutamic acid exert an important influence on the umami taste of fish sauce. Specific metabolites were primarily associated with amino acid metabolism, particularly alterations in arginine and proline metabolism. This study identifies chemical components and provides novel insights into the taste quality of fish sauce due to fermentation. PMID: 31202297 [PubMed - in process]

Interactive effects between cadmium stabilized by palygorskite and mobilized by siderophores from Pseudomonas fluorescens. Ecotoxicol Environ Saf. 2019 Jun 12;181:265-273 Authors: Jiang JJ, Wang JF, Yang P, Xu ZM, He T, Gao Q, Wang LL, Li QS Abstract The application of palygorskite (PAL) for potentially toxic trace elements (Cd2+, Ni2+, etc.) remediation in polluted soil can substantially reduce the bioavailability and toxicity of these hazard materials. However, the secretion of organic acids and siderophores by microorganisms might result in the re-mobilization of cadmium (Cd) in PAL-bound forms (PAL-Cd). In this study, the interactive effects between Cd stabilized by PAL and mobilized by siderophores from Pseudomonas fluorescens were performed with four flask-shaking experimental treatments, namely, strain with or without an ability of siderophores production respectively associated with or without PAL-Cd. The GC-MS and UHPLC-MS test methods were used to analyze the concentrations of metabolites. Results showed that the Cd mobilized by strain with siderophores production was 22.1% higher than that of strain without the ability of siderophores production (p < 0.05). The mobilization of Cd in PAL in turn significantly reduced the siderophores production of Pseudomonas fluorescens by 25.1% (p < 0.05). The numbers of metabolites significantly up-regulated and down-regulated were 9 and 22 in strain groups with PAL-Cd addition compared with the groups without PAL-Cd, respectively. Metabolomics analysis revealed that the mobilized Cd affects the signal transduction pathway and primary metabolic processes, reduces the metabolic capacity of pentose phosphate pathway, glycolysis and tricarboxylic acid cycle pathway. These changes inhibit the ability of strain to biosynthesize amino acids during the mobilization processes, further reducing the capacity of Pseudomonas fluorescens to produce siderophores. This study provides a useful information on how to select soil Cd-stabilizing materials in a targeted manner and how to avoid Cd re-mobilization by siderophores. PMID: 31201958 [PubMed - as supplied by publisher]

Differential plasma postprandial lipidomic responses to krill oil and fish oil supplementations in women: A randomized crossover study. Nutrition. 2019 Apr 25;65:191-201 Authors: Sung HH, Sinclair AJ, Huynh K, Smith AT, Mellett NA, Meikle PJ, Su XQ Abstract OBJECTIVES: There is no convincing evidence that krill oil (KO) consumption results in a higher incorporation of long chain ω-3 polyunsaturated fatty acids into blood lipid fractions than fish oil (FO). This study examined the postprandial plasma lipidomic responses to KO supplementation compared with FO supplementation in healthy women. METHODS: Ten women (aged 18-45 y) consumed a high-fat (15 g of olive oil) breakfast, supplemented with 5 g of KO or FO in a randomized crossover study with a minimum 7-d washout period between the supplementations. Plasma samples collected at the fasting state and at 3 and 5 h postprandially were analyzed using liquid chromatography electrospray ionization-tandem mass spectrometry. RESULTS: After the supplementations, 5 out of 34 lipid classes or subclasses had significantly greater concentrations from KO compared with FO. There were 27 molecular species including 5 ether-phospholipid species, out of a total of 701, which had significant differences between supplementations in the postprandial period. Eicosapentaenoic acid and docosahexaenoic acid from KO were preferentially partitioned toward phospholipid molecular species, whereas eicosapentaenoic acid and docosahexaenoic acid from FO were preferentially partitioned toward neutral lipids. PMID: 31201957 [PubMed - as supplied by publisher]

Related Articles Urine and serum NMR-based metabolomics in pre-procedural prediction of contrast-induced nephropathy. Intern Emerg Med. 2019 Jun 14;: Authors: Dalili N, Chashmniam S, Khoormizi SMH, Salehi L, Jamalian SA, Nafar M, Kalantari S Abstract Contrast induced nephropathy (CIN) has been reported to be the third foremost cause of acute renal failure. Metabolomics is a robust technique that has been used to identify potential biomarkers for the prediction of renal damage. We aim to analyze the serum and urine metabolites changes, before and after using contrast for coronary angiography, to determine if metabolomics can predict early development of CIN. 66 patients undergoing elective coronary angiography were eligible for enrollment. Urine and serum samples were collected prior to administration of CM and 72 h post procedure and analyzed by nuclear magnetic resonance. The significant differential metabolites between patients who develop CIN and patients who have stable renal function after angiography were identified using U test and receiver operating characteristic analysis was performed for each metabolite candidate. Potential susceptible pathways to cytotoxic effect of CM were investigated by pathway analysis. A predictive panel composed of six urinary metabolites had the best area under the curve. Glutamic acid, uridine diphosphate, glutamine and tyrosine were the most important serum predictive biomarkers. Several pathways related to amino acid and nicotinamide metabolism were suggested as impaired pathways in CIN prone patients. Changes exist in urine and serum metabolomics patterns in patients who do and do not develop CIN after coronary angiography hence metabolites may be potential predictive identifiers of CIN. PMID: 31201681 [PubMed - as supplied by publisher]

Related Articles Investigation of the impact of birth by cesarean section on fetal and maternal metabolism. Arch Gynecol Obstet. 2019 Jun 14;: Authors: Shokry E, Marchioro L, Uhl O, Bermúdez MG, García-Santos JA, Segura MT, Campoy C, Koletzko B Abstract PURPOSE: Elective cesarean section (CS) was related to long-term adverse health effects in the offspring, but little is known about underlying mechanisms. Our study investigates the metabolic changes in both maternal and cord blood associated with CS in comparison to vaginal delivery (VD) to explore potential causal pathways. METHODS: Samples obtained from PREOBE study participants were subjected to LC-MS/MS-targeted metabolomics comprising > 200 metabolites. RESULTS: Elective CS showed an impact on both maternal and cord blood metabolomes. In maternal blood, the CS group showed lower levels of phospholipids (PL), principally ether-linked phosphatidylcholines (aaPC), pyruvic acid, branched chain keto-acids (BCKA), and other gluconeogenic substrates, but since the CS group showed different HDL levels in comparison to the VD group, we could not exclude contribution of the latter in the findings. In cord blood, the most remarkable finding in the CS group was the high levels of Cys; conversely, the lower levels of non-esterified fatty acids (NEFA), some tricarboxylic acid (TCA) cycle metabolites, gluconeogenic substrates, markers of β-oxidation, and the sum of hexoses were lower in CS-born babies in addition to tendentially lower levels of PL. CONCLUSIONS: We speculate that lower levels of maternal and fetal corticosteroids in CS, due to less stressful condition, cause metabolic perturbations at birth initiating future negative health outcomes. This further supports the early programming hypothesis. PMID: 31201538 [PubMed - as supplied by publisher]

Related Articles Publisher Correction: Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics. Nat Cell Biol. 2019 Jun 14;: Authors: Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper. PMID: 31201389 [PubMed - as supplied by publisher]

Related Articles Filtering procedures for untargeted LC-MS metabolomics data. BMC Bioinformatics. 2019 Jun 14;20(1):334 Authors: Schiffman C, Petrick L, Perttula K, Yano Y, Carlsson H, Whitehead T, Metayer C, Hayes J, Rappaport S, Dudoit S Abstract BACKGROUND: Untargeted metabolomics datasets contain large proportions of uninformative features that can impede subsequent statistical analysis such as biomarker discovery and metabolic pathway analysis. Thus, there is a need for versatile and data-adaptive methods for filtering data prior to investigating the underlying biological phenomena. Here, we propose a data-adaptive pipeline for filtering metabolomics data that are generated by liquid chromatography-mass spectrometry (LC-MS) platforms. Our data-adaptive pipeline includes novel methods for filtering features based on blank samples, proportions of missing values, and estimated intra-class correlation coefficients. RESULTS: Using metabolomics datasets that were generated in our laboratory from samples of human blood, as well as two public LC-MS datasets, we compared our data-adaptive filtering method with traditional methods that rely on non-method specific thresholds. The data-adaptive approach outperformed traditional approaches in terms of removing noisy features and retaining high quality, biologically informative ones. The R code for running the data-adaptive filtering method is provided at https://github.com/courtneyschiffman/Metabolomics-Filtering . CONCLUSIONS: Our proposed data-adaptive filtering pipeline is intuitive and effectively removes uninformative features from untargeted metabolomics datasets. It is particularly relevant for interrogation of biological phenomena in data derived from complex matrices associated with biospecimens. PMID: 31200644 [PubMed - in process]

Related Articles Metabolomic insights into polyhydroxyalkanoates production by halophilic bacteria with acetic acid as carbon source. Biosci Biotechnol Biochem. 2019 Jun 14;:1-9 Authors: Wang P, Qiu YQ, Chen XT, Liang XF, Ren LH Abstract A metabolomics method was established to analyze changes of intracellular metabolites and study the mechanism for enhancing polyhydroxyalkanoates production by halotolerant bacteria, Bacillus cereus strain HY-3, using acetic acid as carbon source. Maximum poly(3-hydroxybutyrate) (PHB) contents for the medium with 0.5 g/L and 5.0 g/L of acetic acid were 41.0 ± 0.415% and 49.2 ± 1.21%. Principal components analysis revealed clear metabolic differences in different growth stages and different concentrations of carbon source. According to statistical analysis, 3-hydroxybutyrate (3-HB), serine, threonine, malate, and pyruvate were determined as potential biomarkers for PHB production. Moreover, metabolic pathways analysis indicated that high level of 3-HB in death phase was due to the limitation of carbon source. Metabolism of glycine, serine, and threonine was influential pathway for PHB production among amino acid metabolisms. High levels of organic acids from the TCA cycle could stimulate the carbon source flux into PHB biosynthetic pathway. PMID: 31200628 [PubMed - as supplied by publisher]

Related Articles Comparative Metabolomics of Early Development of the Parasitic Plants Phelipanche aegyptiaca and Triphysaria versicolor. Metabolites. 2019 Jun 13;9(6): Authors: Clermont K, Wang Y, Liu S, Yang Z, dePamphilis CW, Yoder JI, Collakova E, Westwood JH Abstract Parasitic weeds of the family Orobanchaceae attach to the roots of host plants via haustoria capable of drawing nutrients from host vascular tissue. The connection of the haustorium to the host marks a shift in parasite metabolism from autotrophy to at least partial heterotrophy, depending on the level of parasite dependence. Species within the family Orobanchaceae span the spectrum of host nutrient dependency, yet the diversity of parasitic plant metabolism remains poorly understood, particularly during the key metabolic shift surrounding haustorial attachment. Comparative profiling of major metabolites in the obligate holoparasite Phelipanche aegyptiaca and the facultative hemiparasite Triphysaria versicolor before and after attachment to the hosts revealed several metabolic shifts implicating remodeling of energy and amino acid metabolism. After attachment, both parasites showed metabolite profiles that were different from their respective hosts. In P. aegyptiaca, prominent changes in metabolite profiles were also associated with transitioning between different tissue types before and after attachment, with aspartate levels increasing significantly after the attachment. Based on the results from 15N labeling experiments, asparagine and/or aspartate-rich proteins were enriched in host-derived nitrogen in T. versicolor. These results point to the importance of aspartate and/or asparagine in the early stages of attachment in these plant parasites and provide a rationale for targeting aspartate-family amino acid biosynthesis for disrupting the growth of parasitic weeds. PMID: 31200467 [PubMed]

Related Articles Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach. Molecules. 2019 Jun 13;24(12): Authors: Marti G, Joulia P, Amiel A, Fabre B, David B, Fabre N, Fiorini-Puybaret C Abstract Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent. PMID: 31200456 [PubMed - in process]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

44 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα). Ecotoxicol Environ Saf. 2019 Jun 08;181:164-171 Authors: Gong Y, Zhang H, Geng N, Ren X, Giesy JP, Luo Y, Xing L, Wu P, Yu Z, Chen J Abstract Short-chain chlorinated paraffins (SCCPs) are frequently detected in environmental matrices and human tissues. It was hypothesized that SCCPs might interact with the peroxisome proliferator-activated receptor α (PPARα). In the present study, an in vitro, dual-luciferase reporter gene assay and in silico molecular docking analysis were employed together to study the interactions between SCCPs congeners and PPARα. Expressions of genes downstream in pathways activated by PPARα in liver of rats exposed to 1, 10, or 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) for 28 days were examined to confirm activation potencies of SCCPs toward PPARα signaling. Effects of exposure to C10-13-CPs (56.5% Cl) on fatty acid metabolism in rat liver were also explored via a pseudo-targeted metabolomics strategy. Our results showed that C10-13-CPs (56.5% Cl) caused a dose-dependent greater expression of luciferase activity of rat PPARα. Molecular docking modeling revealed that SCCPs had a strong capacity to bind with PPARα only through hydrophobic interactions and the binding affinity was dependent on the degree of chlorination in SCCPs congeners. In livers of male rats, exposure to 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) resulted in up-regulated expressions of 11 genes that are downstream in the PPARα-activated pathway and regulate catabolism of fatty acid. Consistently, accelerated fatty acid oxidation was observed mainly characterized by lesser concentrations of ∑fatty acids in livers of rats. Overall, these results demonstrated, for the first time, that SCCPs could activate rat PPARα signaling and thereby disrupt metabolism of fatty acid in livers of male rats. PMID: 31185430 [PubMed - as supplied by publisher]

Metabolomic profiling of CHO fed-batch growth phases at 10, 100 and 1000 L. Biotechnol Bioeng. 2019 Jun 11;: Authors: Vodopivec M, Lah L, Narat M, Curk T Abstract Established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement and the measurement of physicochemical qualities of the cultivation medium. These methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. However, understanding of the latter is essential for optimization of bioprocess development. Our study employed LC-MS metabolomics as a tool for additional resolution of bioprocess monitoring and was designed at three bioreactors scales (10 L, 100 L, 1000 L) to gain insight into the basal metabolic states of the Chinese hamster ovary (CHO) cell culture during fed-batch. Metabolites characteristic of the four growth stages (early and late exponential phase, stationary phase, and the phase of decline) were identified by multivariate analysis. Enriched metabolic pathways were then established for each growth phase using the CHO metabolic network model. Biomass generation and nucleotide synthesis were enriched in early exponential phase, followed by increased protein production and imbalanced glutathione metabolism in late exponential phase. Glycolysis became downregulated in stationary phase and amino-acid metabolism increased. Phase of culture decline resulted in rise of oxidized glutathione and fatty acid concentrations. Intracellular metabolic profiles of the CHO fed-batch culture were also shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale. This article is protected by copyright. All rights reserved. PMID: 31184374 [PubMed - as supplied by publisher]