Metabolites

9 pages, 319 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Metabolites in 2019

by Metabolites Editorial Office

Metabolites 2020, 10(1), 41; https://doi.org/10.3390/metabo10010041 - 17 Jan 2020

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Abstract

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12 pages, 1885 KiB

Open AccessArticle

Study of the Royal Jelly Free Fatty Acids by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS)

by Maroula G. Kokotou, Christiana Mantzourani, Rodalia Babaiti and George Kokotos

Metabolites 2020, 10(1), 40; https://doi.org/10.3390/metabo10010040 - 16 Jan 2020

Cited by 19 | Viewed by 4695

Abstract

The lipidome of royal jelly (RJ) consists of medium-chained (8–12 carbon atoms) free fatty acids. We present herein a liquid chromatography-high resolution mass spectrometry (HRMS) method that permits the determination of RJ fatty acids and at the same time the detection of suspect [...] Read more.

The lipidome of royal jelly (RJ) consists of medium-chained (8–12 carbon atoms) free fatty acids. We present herein a liquid chromatography-high resolution mass spectrometry (HRMS) method that permits the determination of RJ fatty acids and at the same time the detection of suspect fatty acids. The method allows for the direct quantification of seven free fatty acids of RJ, avoiding any derivatization step. It was validated and applied in seven RJ samples, where the major RJ fatty acid trans-10-hydroxy-2-decenoic acid (10-HDA) was found to vary from 0.771 ± 0.08 to 0.928 ± 0.04 g/100 g fresh RJ. Four additional suspect fatty acids were simultaneously detected taking advantage of the HRMS detection. Full article

(This article belongs to the Special Issue Compound Identification of Small Molecules)

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12 pages, 1145 KiB

Open AccessArticle

Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions

by Sonia Del Prete, Andrea Angeli, Cynthia Ghobril, Julien Hitce, Cécile Clavaud, Xavier Marat, Claudiu T. Supuran and Clemente Capasso

Metabolites 2020, 10(1), 39; https://doi.org/10.3390/metabo10010039 - 16 Jan 2020

Cited by 18 | Viewed by 3015

Abstract

The critical CO₂ hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO₂ and HCO₃⁻ at the cellular level, which will not be ensured [...] Read more.

The critical CO₂ hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO₂ and HCO₃⁻ at the cellular level, which will not be ensured by the low velocity of the uncatalyzed reaction. CA inhibition may impair the growth of microorganisms. In the yeasts, Candida albicans and Malassezia globosa, the activity of the unique β-CA identified in their genomes was demonstrated to be essential for growth of the pathogen. Here, we decided to investigate the sulfonamide inhibition profile of the homologous β-CA (MreCA) identified in the genome of Malassezia restricta, an opportunistic pathogen triggering dandruff and seborrheic dermatitis. Among 40 investigated derivatives, the best MreCA sulfonamide inhibitors were dorzolamide, brinzolamide, indisulam, valdecoxib, sulthiam, and acetazolamide (K_I < 1.0 μM). The MreCA inhibition profile was different from those of the homologous enzyme from Malassezia globosa (MgCA) and the human isoenzymes (hCA I and hCA II). These results might be useful to for designing CA inhibitor scaffolds that may selectively inhibit the dandruff-producing fungi. Full article

(This article belongs to the Special Issue Carbonic Anhydrases and Metabolism Volume 2)

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14 pages, 1991 KiB

Open AccessArticle

Comparative Analysis of β-Carotene Production by Mucor circinelloides Strains CBS 277.49 and WJ11 under Light and Dark Conditions

by Tahira Naz, Shaista Nosheen, Shaoqi Li, Yusuf Nazir, Kiren Mustafa, Qing Liu, Victoriano Garre and Yuanda Song

Metabolites 2020, 10(1), 38; https://doi.org/10.3390/metabo10010038 - 16 Jan 2020

Cited by 22 | Viewed by 3290

Abstract

Carotenoids are natural potent antioxidants and free radical scavengers which are able to modulate the pathogenesis of some cancers and heart diseases in human, indicating their importance in being provided through the diet. Mucor circinelloides accumulates β-carotene as the main carotenoid compound and [...] Read more.

Carotenoids are natural potent antioxidants and free radical scavengers which are able to modulate the pathogenesis of some cancers and heart diseases in human, indicating their importance in being provided through the diet. Mucor circinelloides accumulates β-carotene as the main carotenoid compound and has been used as a model organism in carotenogenic studies. In the present study, the potential of two M. circinelloides strains to accumulate β-carotene was investigated under light and dark conditions. The results, which were quantitated by HPLC, showed that CBS 277.49 accumulated higher pigment in comparison to WJ11 under both conditions. Continuous illumination triggered the pigment accumulation up to 2.7-fold in strain CBS 277.49 and 2.2-fold in strain WJ11 in comparison to dark. The mRNA analysis of the four key genes involved in isoprenoid pathway by RT-qPCR showed higher transcriptional levels in CBS 277.49 as compared to WJ11, indicating that the pigment production metabolic machinery is more active in CBS 277.49 strain. A new scope for further research was established by this work for improved β-carotene production in the high producing strain CBS 277.49. Full article

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30 pages, 917 KiB

Open AccessEditor’s ChoiceReview

Metabolomics in the Context of Plant Natural Products Research: From Sample Preparation to Metabolite Analysis

by Mohamed A. Salem, Leonardo Perez de Souza, Ahmed Serag, Alisdair R. Fernie, Mohamed A. Farag, Shahira M. Ezzat and Saleh Alseekh

Metabolites 2020, 10(1), 37; https://doi.org/10.3390/metabo10010037 - 15 Jan 2020

Cited by 159 | Viewed by 13560

Abstract

Plant-derived natural products have long been considered a valuable source of lead compounds for drug development. Natural extracts are usually composed of hundreds to thousands of metabolites, whereby the bioactivity of natural extracts can be represented by synergism between several metabolites. However, isolating [...] Read more.

Plant-derived natural products have long been considered a valuable source of lead compounds for drug development. Natural extracts are usually composed of hundreds to thousands of metabolites, whereby the bioactivity of natural extracts can be represented by synergism between several metabolites. However, isolating every single compound from a natural extract is not always possible due to the complex chemistry and presence of most secondary metabolites at very low levels. Metabolomics has emerged in recent years as an indispensable tool for the analysis of thousands of metabolites from crude natural extracts, leading to a paradigm shift in natural products drug research. Analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are used to comprehensively annotate the constituents of plant natural products for screening, drug discovery as well as for quality control purposes such as those required for phytomedicine. In this review, the current advancements in plant sample preparation, sample measurements, and data analysis are presented alongside a few case studies of the successful applications of these processes in plant natural product drug discovery. Full article

(This article belongs to the Special Issue Sample Preparation in Metabolomics)

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14 pages, 1401 KiB

Open AccessArticle

Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

by Nataliya Chorna, Josefina Romaguera and Filipa Godoy-Vitorino

Metabolites 2020, 10(1), 36; https://doi.org/10.3390/metabo10010036 - 15 Jan 2020

Cited by 22 | Viewed by 4791

Abstract

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid [...] Read more.

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity. Full article

(This article belongs to the Special Issue Metabolomics and Multi-Omics Integration)

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11 pages, 1045 KiB

Open AccessArticle

Metabolomic Profiling of Fungal Pathogens Responsible for Root Rot in American Ginseng

by Natasha DesRochers, Jacob P. Walsh, Justin B. Renaud, Keith A. Seifert, Ken K.-C. Yeung and Mark W. Sumarah

Metabolites 2020, 10(1), 35; https://doi.org/10.3390/metabo10010035 - 14 Jan 2020

Cited by 25 | Viewed by 3967

Abstract

Ginseng root is an economically valuable crop in Canada at high risk of yield loss caused by the pathogenic fungus Ilyonectria mors-panacis, formerly known as Cylindrocarpon destructans. While this pathogen has been well-characterized from morphological and genetic perspectives, little is known about [...] Read more.

Ginseng root is an economically valuable crop in Canada at high risk of yield loss caused by the pathogenic fungus Ilyonectria mors-panacis, formerly known as Cylindrocarpon destructans. While this pathogen has been well-characterized from morphological and genetic perspectives, little is known about the secondary metabolites it produces and their role in pathogenicity. We used an untargeted tandem liquid chromatography-mass spectrometry (LC-MS)-based approach paired with global natural products social molecular networking (GNPS) to compare the metabolite profiles of virulent and avirulent Ilyonectria strains. The ethyl acetate extracts of 22 I. mors-panacis strains and closely related species were analyzed by LC-MS/MS. Principal component analysis of LC-MS features resulted in two distinct groups, which corresponded to virulent and avirulent Ilyonectria strains. Virulent strains produced more types of compounds than the avirulent strains. The previously reported I. mors-panacis antifungal compound radicicol was present. Additionally, a number of related resorcyclic acid lactones (RALs) were putatively identified, namely pochonins and several additional derivatives of radicicol. Pochonins have not been previously reported in Ilyonectria spp. and have documented antimicrobial activity. This research contributes to our understanding of I. mors-panacis natural products and its pathogenic relationship with ginseng. Full article

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18 pages, 1816 KiB

Open AccessArticle

Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids

by Arnaud Germain, Dinesh K. Barupal, Susan M. Levine and Maureen R. Hanson

Metabolites 2020, 10(1), 34; https://doi.org/10.3390/metabo10010034 - 14 Jan 2020

Cited by 47 | Viewed by 16923

Abstract

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 [...] Read more.

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways. Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds. The most intriguing finding concerns acyl cholines, belonging to the fatty acid metabolism sub-pathway of lipids, for which all compounds are consistently reduced in two distinct ME/CFS patient cohorts. We compiled the extremely limited knowledge about these compounds and regard them as promising in the quest to explain many of the ME/CFS symptoms. Another class of lipids with far-reaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort. We also report on lower dipeptides and elevated sphingolipids abundance in patients compared to controls. Disturbances in the metabolism of many of these molecules can be linked to the profound organ system symptoms endured by ME/CFS patients. Full article

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14 pages, 2382 KiB

Open AccessArticle

Discovering Temporal Patterns in Longitudinal Nontargeted Metabolomics Data via Group and Nuclear Norm Regularized Multivariate Regression

by Zhaozhou Lin, Qiao Zhang, Shengyun Dai and Xiaoyan Gao

Metabolites 2020, 10(1), 33; https://doi.org/10.3390/metabo10010033 - 13 Jan 2020

Cited by 3 | Viewed by 2215

Abstract

Temporal associations in longitudinal nontargeted metabolomics data are generally ignored by common pattern recognition methods such as partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA). To discover temporal patterns in longitudinal metabolomics, a multitask learning (MTL) method [...] Read more.

Temporal associations in longitudinal nontargeted metabolomics data are generally ignored by common pattern recognition methods such as partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA). To discover temporal patterns in longitudinal metabolomics, a multitask learning (MTL) method employing structural regularization was proposed. The group regularization term of the proposed MTL method enables the selection of a small number of tentative biomarkers while maintaining high prediction accuracy. Meanwhile, the nuclear norm imposed into the regression coefficient accounts for the interrelationship of the metabolomics data obtained on consecutive time points. The effectiveness of the proposed method was demonstrated by comparison study performed on a metabolomics dataset and a simulating dataset. The results showed that a compact set of tentative biomarkers charactering the whole antipyretic process of Qingkailing injection were selected with the proposed method. In addition, the nuclear norm introduced in the new method could help the group norm to improve the method’s recovery ability. Full article

(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics: Challenges and Applications)

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26 pages, 815 KiB

Open AccessReview

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease

by Camila Weschenfelder, Alexandre Schaan de Quadros, Julia Lorenzon dos Santos, Silvia Bueno Garofallo and Aline Marcadenti

Metabolites 2020, 10(1), 32; https://doi.org/10.3390/metabo10010032 - 11 Jan 2020

Cited by 23 | Viewed by 5105

Abstract

Adipose tissue is a complex structure responsible for fat storage and releasing polypeptides (adipokines) and metabolites, with systemic actions including body weight balance, appetite regulation, glucose homeostasis, and blood pressure control. Signals sent from different tissues are generated and integrated in adipose tissue; [...] Read more.

Adipose tissue is a complex structure responsible for fat storage and releasing polypeptides (adipokines) and metabolites, with systemic actions including body weight balance, appetite regulation, glucose homeostasis, and blood pressure control. Signals sent from different tissues are generated and integrated in adipose tissue; thus, there is a close connection between this endocrine organ and different organs and systems such as the gut and the cardiovascular system. It is known that functional foods, especially different nuts, may be related to a net of molecular mechanisms contributing to cardiometabolic health. Despite being energy-dense foods, nut consumption has been associated with no weight gain, weight loss, and lower risk of becoming overweight or obese. Several studies have reported beneficial effects after nut consumption on glucose control, appetite suppression, metabolites related to adipose tissue and gut microbiota, and on adipokines due to their fatty acid profile, vegetable proteins, l-arginine, dietary fibers, vitamins, minerals, and phytosterols. The aim of this review is to briefly describe possible mechanisms implicated in weight homeostasis related to different nuts, as well as studies that have evaluated the effects of nut consumption on adipokines and metabolites related to adipose tissue and gut microbiota in animal models, healthy individuals, and primary and secondary cardiovascular prevention. Full article

(This article belongs to the Special Issue Metabolic Health and Weight)

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23 pages, 4045 KiB

Open AccessArticle

Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies

by Mohammed S. Hifnawy, Mahmoud A. Aboseada, Hossam M. Hassan, Asmaa M. AboulMagd, Adel F. Tohamy, Samraa H. Abdel-Kawi, Mostafa E. Rateb, El Moataz Bellah El Naggar, Miaomiao Liu, Ronald J. Quinn, Hani A. Alhadrami and Usama Ramadan Abdelmohsen

Metabolites 2020, 10(1), 31; https://doi.org/10.3390/metabo10010031 - 11 Jan 2020

Cited by 14 | Viewed by 3785

Abstract

Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of [...] Read more.

Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten different plant extracts on testicular spermatogenesis. The correlation between the chemical profile of these extracts and their in vivo effect on male reproductive system was evaluated using various techniques. Approximately 10% of LD₅₀ of hydro-methanolic extracts were orally administrated to rats for 60 days. Semen parameters, sexual organ weights, and serum levels of male sex hormones in addition to testes histopathology, were evaluated. Moreover, metabolomic analysis using (LC-HRESIMS), multivariate analysis (PCA), immunohistochemistry (caspase-3 and β-catenin), and a docking study were performed. Results indicated that three plant extracts significantly decreased epididymal sperm density and motility. Moreover, their effects on testicular cells were also assured by histopathological evaluations. Metabolomic profiling of the bioactive plant extracts showed the presence of diverse phytochemicals, mostly oleanane saponins, phenolic diterpenes, and lupane triterpenes. A docking study on caspase-3 enzyme showed that oleanane saponins possessed the highest binding affinity. An immunohistochemistry assay on β-catenin and caspase-3 indicated that Albizzia lebbeck was the most active extract for decreasing immunoexpression of β-catenin, while Rosmarinus officinalis showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of A. lebbeck, Anagallis arvensis, and R. officinalis can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells. Full article

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11 pages, 2118 KiB

Open AccessArticle

Liquid Chromatography Tandem Mass Spectrometry Quantification of ¹³C-Labeling in Sugars

by Jean-Christophe Cocuron, Zacchary Ross and Ana P. Alonso

Metabolites 2020, 10(1), 30; https://doi.org/10.3390/metabo10010030 - 10 Jan 2020

Cited by 6 | Viewed by 3488

Abstract

Subcellular compartmentation has been challenging in plant ¹³C-metabolic flux analysis. Indeed, plant cells are highly compartmented: they contain vacuoles and plastids in addition to the regular organelles found in other eukaryotes. The distinction of reactions between compartments is possible when metabolites are [...] Read more.

Subcellular compartmentation has been challenging in plant ¹³C-metabolic flux analysis. Indeed, plant cells are highly compartmented: they contain vacuoles and plastids in addition to the regular organelles found in other eukaryotes. The distinction of reactions between compartments is possible when metabolites are synthesized in a particular compartment or by a unique pathway. Sucrose is an example of such a metabolite: it is specifically produced in the cytosol from glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P). Therefore, determining the ¹³C-labeling in the fructosyl and glucosyl moieties of sucrose directly informs about the labeling of cytosolic F6P and G6P, respectively. To date, the most commonly used method to monitor sucrose labeling is by nuclear magnetic resonance, which requires substantial amounts of biological sample. This study describes a new methodology that accurately measures the labeling in free sugars using liquid chromatography tandem mass spectrometry (LC-MS/MS). For this purpose, maize embryos were pulsed with [U-¹³C]-fructose, intracellular sugars were extracted, and their time-course labeling was analyzed by LC-MS/MS. Additionally, extracts were enzymatically treated with hexokinase to remove the soluble hexoses, and then invertase to cleave sucrose into fructose and glucose. Finally, the labeling in the glucosyl and fructosyl moieties of sucrose was determined by LC-MS/MS. Full article

(This article belongs to the Special Issue Metabolomic and Flux Analysis in Plants)

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16 pages, 3027 KiB

Open AccessArticle

Biotransformation of Silymarin Flavonolignans by Human Fecal Microbiota

by Kateřina Valentová, Jaroslav Havlík, Pavel Kosina, Barbora Papoušková, José Diógenes Jaimes, Kristýna Káňová, Lucie Petrásková, Jitka Ulrichová and Vladimír Křen

Metabolites 2020, 10(1), 29; https://doi.org/10.3390/metabo10010029 - 09 Jan 2020

Cited by 23 | Viewed by 3972

Abstract

Flavonolignans occur typically in Silybum marianum (milk thistle) fruit extract, silymarin, which contains silybin, isosilybin, silychristin, silydianin, and their 2,3-dehydroderivatives, together with other minor flavonoids and a polymeric phenolic fraction. Biotransformation of individual silymarin components by human microbiota was studied ex vivo, using [...] Read more.

Flavonolignans occur typically in Silybum marianum (milk thistle) fruit extract, silymarin, which contains silybin, isosilybin, silychristin, silydianin, and their 2,3-dehydroderivatives, together with other minor flavonoids and a polymeric phenolic fraction. Biotransformation of individual silymarin components by human microbiota was studied ex vivo, using batch incubations inoculated by fecal slurry. Samples at selected time points were analyzed by ultrahigh-performance liquid chromatography equipped with mass spectrometry. The initial experiment using a concentration of 200 mg/L showed that flavonolignans are resistant to the metabolic action of intestinal microbiota. At the lower concentration of 10 mg/L, biotransformation of flavonolignans was much slower than that of taxifolin, which was completely degraded after 16 h. While silybin, isosilybin, and 2,3-dehydrosilybin underwent mostly demethylation, silychristin was predominantly reduced. Silydianin, 2,3-dehydrosilychristin and 2,3-dehydrosilydianin were reduced, as well, and decarbonylation and cysteine conjugation proceeded. No low-molecular-weight phenolic metabolites were detected for any of the compounds tested. Strong inter-individual differences in the biotransformation profile were observed among the four fecal-material donors. In conclusion, the flavonolignans, especially at higher (pharmacological) doses, are relatively resistant to biotransformation by gut microbiota, which, however, depends strongly on the individual structures of these isomeric compounds, but also on the stool donor. Full article

(This article belongs to the Special Issue Gut Metabolism of Natural Products)

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13 pages, 2845 KiB

Open AccessArticle

A Case Report of Switching from Specific Vendor-Based to R-Based Pipelines for Untargeted LC-MS Metabolomics

by Álvaro Fernández-Ochoa, Rosa Quirantes-Piné, Isabel Borrás-Linares, María de la Luz Cádiz-Gurrea, PRECISESADS Clinical Consortium, Marta E. Alarcón Riquelme, Carl Brunius and Antonio Segura-Carretero

Metabolites 2020, 10(1), 28; https://doi.org/10.3390/metabo10010028 - 08 Jan 2020

Cited by 13 | Viewed by 4441

Abstract

Data pre-processing of the LC-MS data is a critical step in untargeted metabolomics studies in order to achieve correct biological interpretations. Several tools have been developed for pre-processing, and these can be classified into either commercial or open source software. This case report [...] Read more.

Data pre-processing of the LC-MS data is a critical step in untargeted metabolomics studies in order to achieve correct biological interpretations. Several tools have been developed for pre-processing, and these can be classified into either commercial or open source software. This case report aims to compare two specific methodologies, Agilent Profinder vs. R pipeline, for a metabolomic study with a large number of samples. Specifically, 369 plasma samples were analyzed by HPLC-ESI-QTOF-MS. The collected data were pre-processed by both methodologies and later evaluated by several parameters (number of peaks, degree of missingness, quality of the peaks, degree of misalignments, and robustness in multivariate models). The vendor software was characterized by ease of use, friendly interface and good quality of the graphs. The open source methodology could more effectively correct the drifts due to between and within batch effects. In addition, the evaluated statistical methods achieved better classification results with higher parsimony for the open source methodology, indicating higher data quality. Although both methodologies have strengths and weaknesses, the open source methodology seems to be more appropriate for studies with a large number of samples mainly due to its higher capacity and versatility that allows combining different packages, functions, and methods in a single environment. Full article

(This article belongs to the Special Issue Metabolomics Methodologies and Applications)

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22 pages, 9924 KiB

Open AccessArticle

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI

by Fang Tian, Runzhe Liu, Chaoxin Fan, Yi Sun, Xi Huang, Zongxiu Nie, Xin Zhao and Xiaoping Pu

Metabolites 2020, 10(1), 27; https://doi.org/10.3390/metabo10010027 - 07 Jan 2020

Cited by 23 | Viewed by 3814

Abstract

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation [...] Read more.

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism. Full article

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12 pages, 1509 KiB

Open AccessArticle

Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS

by Vivaldy Prinville, Leanne Ohlund and Lekha Sleno

Metabolites 2020, 10(1), 26; https://doi.org/10.3390/metabo10010026 - 07 Jan 2020

Cited by 11 | Viewed by 5360

Abstract

Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to [...] Read more.

Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to study the variation of individual circulating bile acids in the context of hepatotoxity or liver disease. Acetaminophen (APAP), a drug commonly taken to relieve pain and decrease fever, is known to cause acute liver failure at high doses. We have developed a targeted liquid chromatography-tandem mass spectrometry method to monitor the effects of different doses of APAP on the bile acid plasma profile in a rat model. The analysis method was optimized to ensure chromatographic resolution of isomeric species using a mixture of 46 standard bile acids, and 14 isotopically-labeled internal standard (IS) compounds detected in multiple reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. Four doses of acetaminophen were studied, the highest of which shows signs of hepatotoxicity in rats. This targeted method revealed that high dose APAP has an important effect on bile acid profiles. Changes were seen in several unconjugated bile acids as well as glycine conjugates; however, no obvious changes were apparent for taurine-conjugated species. Full article

(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)

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1 pages, 146 KiB

Open AccessErratum

Erratum: Ismail, I.T.; et al. Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics. Metabolites 2019, 9, 242

by Israa T. Ismail, Megan R. Showalter and Oliver Fiehn

Metabolites 2020, 10(1), 25; https://doi.org/10.3390/metabo10010025 - 06 Jan 2020

Cited by 4 | Viewed by 1997

Abstract

The authors wish to make the following correction to this paper [...] Full article

16 pages, 1606 KiB

Open AccessArticle

Metabolomics Provide Sensitive Insights into the Impacts of Low Level Environmental Contamination on Fish Health—A Pilot Study

by Sara M. Long, Dedreia L. Tull, David P. De Souza, Konstantinos A. Kouremenos, Saravanan Dayalan, Malcolm J. McConville, Kathryn L. Hassell, Vincent J. Pettigrove and Marthe Monique Gagnon

Metabolites 2020, 10(1), 24; https://doi.org/10.3390/metabo10010024 - 06 Jan 2020

Cited by 8 | Viewed by 3301

Abstract

This exploratory study aims to investigate the health of sand flathead (Platycephalus bassensis) sampled from five sites in Port Phillip Bay, Australia using gas chromatography-mass spectrometry (GC-MS) metabolomics approaches. Three of the sites were the recipients of industrial, agricultural, and urban [...] Read more.

This exploratory study aims to investigate the health of sand flathead (Platycephalus bassensis) sampled from five sites in Port Phillip Bay, Australia using gas chromatography-mass spectrometry (GC-MS) metabolomics approaches. Three of the sites were the recipients of industrial, agricultural, and urban run-off and were considered urban sites, while the remaining two sites were remote from contaminant inputs, and hence classed as rural sites. Morphological parameters as well as polar and free fatty acid metabolites were used to investigate inter-site differences in fish health. Significant differences in liver somatic index (LSI) and metabolite abundance were observed between the urban and rural sites. Differences included higher LSI, an increased abundance of amino acids and energy metabolites, and reduced abundance of free fatty acids at the urban sites compared to the rural sites. These differences might be related to the additional energy requirements needed to cope with low-level contaminant exposure through energy demanding processes such as detoxification and antioxidant responses as well as differences in diet between the sites. In this study, we demonstrate that metabolomics approaches can offer a greater level of sensitivity compared to traditional parameters such as physiological parameters or biochemical markers of fish health, most of which showed no or little inter-site differences in the present study. Moreover, the metabolite responses are more informative than traditional biomarkers in terms of biological significance as disturbances in specific metabolic pathways can be identified. Full article

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18 pages, 2112 KiB

Open AccessArticle

Phytohormone and Transcriptomic Analysis Reveals Endogenous Cytokinins Affect Kiwifruit Growth under Restricted Carbon Supply

by Simona Nardozza, Janine Cooney, Helen L. Boldingh, Katrin G. Hewitt, Tania Trower, Dan Jones, Amali H. Thrimawithana, Andrew C. Allan and Annette C. Richardson

Metabolites 2020, 10(1), 23; https://doi.org/10.3390/metabo10010023 - 04 Jan 2020

Cited by 26 | Viewed by 3529

Abstract

Following cell division, fruit growth is characterized by both expansion through increases in cell volume and biomass accumulation in cells. Fruit growth is limited by carbon starvation; however, the mechanism controlling fruit growth under restricted carbohydrate supply is poorly understood. In a previous [...] Read more.

Following cell division, fruit growth is characterized by both expansion through increases in cell volume and biomass accumulation in cells. Fruit growth is limited by carbon starvation; however, the mechanism controlling fruit growth under restricted carbohydrate supply is poorly understood. In a previous study using red-fleshed kiwifruit, we showed that long-term carbon starvation had detrimental effects on carbohydrate, anthocyanin metabolism, and fruit growth. To elucidate the mechanisms underlying the reduction in fruit growth during kiwifruit development, we integrated phytohormone profiling with transcriptomic and developmental datasets for fruit under high or low carbohydrate supplies. Phytohormone profiling of the outer pericarp tissue of kiwifruit showed a 6-fold reduction in total cytokinin concentrations in carbon-starved fruit, whilst other hormones were less affected. Principal component analysis visualised that cytokinin composition was distinct between fruit at 16 weeks after mid bloom, based on their carbohydrate supply status. Cytokinin biosynthetic genes (IPT, CYP735A) were significantly downregulated under carbon starvation, in agreement with the metabolite data. Several genes that code for expansins, proteins involved in cell wall loosening, were also downregulated under carbon starvation. In contrast to other fleshy fruits, our results suggest that cytokinins not only promote cell division, but also drive fruit cell expansion and growth in kiwifruit. Full article

(This article belongs to the Special Issue Fruit Metabolism and Metabolomics)

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11 pages, 1154 KiB

Open AccessArticle

Direct Implementation of Intestinal Permeability Test in NMR Metabolomics for Simultaneous Biomarker Discovery—A Feasibility Study in a Preterm Piglet Model

by Masoumeh Alinaghi, Duc Ninh Nguyen, Per Torp Sangild and Hanne Christine Bertram

Metabolites 2020, 10(1), 22; https://doi.org/10.3390/metabo10010022 - 01 Jan 2020

Cited by 6 | Viewed by 3220

Abstract

Measurement of intestinal permeability (IP) is often used in the examination of inflammatory gastrointestinal disorders. IP can be assessed by measurement of urinary recovery of ingested non-metabolizable lactulose (L) and mannitol (M). The present study aimed to examine how measurements of IP can [...] Read more.

Measurement of intestinal permeability (IP) is often used in the examination of inflammatory gastrointestinal disorders. IP can be assessed by measurement of urinary recovery of ingested non-metabolizable lactulose (L) and mannitol (M). The present study aimed to examine how measurements of IP can be integrated in a NMR-based metabolomics approach for a simultaneous quantification of L/M ratio and biomarker exploration. For this purpose, plasma and urine samples were collected from five-day-old preterm piglets (n = 20) with gastrointestinal disorders (subjected to intra-amniotic lipopolysaccharide (LPS, 1 mg/fetus)) after they had been administrated a 5% lactulose and 5% mannitol solution (15 mL/kg). The collected plasma and urine samples were analyzed by ¹H NMR-based metabolomics. Urine L/M ratio measured by ¹H NMR spectroscopy showed high correlation with the standard measurement of the urinary recoveries by enzymatic assays (r = 0.93, p < 0.05). Partial least squares (PLS) regressions and correlation analyses between L/M ratio and NMR metabolomics data revealed that L/M ratio was positively correlated with plasma lactate, acetate and succinate levels and negatively correlated with urinary hippuric acid and glycine. In conclusion, the present study demonstrated that NMR metabolomics enables simultaneous IP testing and discovery of biomarkers associated with an impaired intestinal permeability. Full article

(This article belongs to the Special Issue Metabolomics Methodologies and Applications)

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12 pages, 1776 KiB

Open AccessArticle

Metabolite Profiling and Classification of Developing Styrax tonkinensis Kernels

by Qikui Wu, Xue Zhao, Chen Chen, Zihan Zhang and Fangyuan Yu

Metabolites 2020, 10(1), 21; https://doi.org/10.3390/metabo10010021 - 01 Jan 2020

Cited by 15 | Viewed by 3297

Abstract

Background: Styrax tonkinensis is an economic tree species with high timber, medicine, oil, and ornamental value. Its seed, containing a particularly high oil content, are widely studied for their biodiesel properties by nutritional components and oil body ultrastructure. However, their comprehensive biochemical compositions [...] Read more.

Background: Styrax tonkinensis is an economic tree species with high timber, medicine, oil, and ornamental value. Its seed, containing a particularly high oil content, are widely studied for their biodiesel properties by nutritional components and oil body ultrastructure. However, their comprehensive biochemical compositions have not been studied. Methods: During S. tonkinensis kernel development, we collected samples from four time points for metabolite profiling and classification through gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Results: A total of 187 and 1556 metabolites were obtained, respectively. All of the metabolites were grouped into 19 and 21 classes by their chemical properties and into 8 clusters based on their change trends, respectively. Among all the metabolites, carboxylic acids and derivatives, flavonoids, fatty acyls, glycerophospholipids, organooxygen compounds, prenol lipids, and steroids and steroid derivatives were the main components. Alanine, glutamine, tryptophan, tyrosine and valine were the five most abundant amino acids. Palmitic acid, stearic acid, oleic acid and linoleic acid were the four major free fatty acids. Flavans, flavonoid glycosides and o-methylated flavonoids were the three major flavonoids. The differential metabolites distributions between different time points were identified. A pathway enrichment was performed, which was mainly focused on three groups, amino acids metabolism, carbon flow from sucrose to lipid and secondary metabolites biosynthesis. Conclusions: It’s the first time to analyze the metabolite fingerprinting for developing S. tonkinensis kernels and identify varied kinds of flavonoids. We performed metabolite profiling, classification and pathway enrichment to assess the comprehensive biochemical compositions. Our results described the change in major metabolites and main metabolic processes during S. tonkinensis kernel development and provided a variety of bases for seed applications as biofuel or medicine. Full article

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15 pages, 5307 KiB

Open AccessArticle

Dynamic Changes in Serum Metabolomic Profiles of Growing Pigs Induced by Intravenous Infusion of Sodium Butyrate

by Hongyu Wang, Erdu Ren, Xiaoe Xiang, Yong Su and Weiyun Zhu

Metabolites 2020, 10(1), 20; https://doi.org/10.3390/metabo10010020 - 01 Jan 2020

Cited by 7 | Viewed by 3431

Abstract

This study aimed to explore the dynamic changes in metabolite profiles and metabolism pathways in the serum of growing pigs by intravenous infusion of sodium butyrate (SB). Fourteen crossbred growing barrows (BW = 23.70 ± 1.29 kg) fitted with jugular cannula were randomly [...] Read more.

This study aimed to explore the dynamic changes in metabolite profiles and metabolism pathways in the serum of growing pigs by intravenous infusion of sodium butyrate (SB). Fourteen crossbred growing barrows (BW = 23.70 ± 1.29 kg) fitted with jugular cannula were randomly allocated to the SB and control (Con) groups, each group consisted of seven replicates (pens), with one pig per pen. At 9:00 of each day during the experimental period, pigs in the SB group were infused with 10 mL of SB (200 mmol/L, pH 7.4, 37 °C) via precaval vein, while the Con group was treated with the same volume of physiological saline. On day 4, the blood of each pig was collected at 0, 30, 60, and 120 min after the intravenous infusion. Metabolites in the serum were detected by gas chromatograph-mass spectrometry analysis. Pathway analysis of metabolomic profiles showed that the differential metabolites mainly enriched in amino acid metabolism, lipid-related metabolism, and the tricarboxylic acid (TCA) cycle. More importantly, the relative concentrations of all eight essential amino acids, five non-essential amino acids, and two amino acid derivatives were decreased by the parenteral SB. In addition, SB significantly increased the relative concentrations of eicosanoic acid and octadecanoic acid and decreased the relative concentration of glycerol-3-phosphate at 0 min (three days after intravenous infusion of SB), which suggests that parenteral SB may increase stearates mobilization and decrease the biosynthesis of stearates. In conclusion, intravenous infusion of SB may induce more amino acids to synthesize proteins and affect fat metabolism through increasing fat mobilization and decreasing the biosynthesis of stearates. However, a further study is needed to understand the mechanism of extensive metabolic pathway changes induced by parenteral SB. Full article

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11 pages, 226 KiB

Open AccessReview

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

by Gabriele Dossi, Letizia Squarcina and Mario Rango

Metabolites 2020, 10(1), 19; https://doi.org/10.3390/metabo10010019 - 28 Dec 2019

Cited by 7 | Viewed by 2762

Abstract

Parkinson’s disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy (³¹P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered [...] Read more.

Parkinson’s disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy (³¹P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 ³¹P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development. Full article

(This article belongs to the Special Issue Mitochondria and Metabolism in Disorders)

15 pages, 2105 KiB

Open AccessArticle

On the Inverse Correlation of Protein and Oil: Examining the Effects of Altered Central Carbon Metabolism on Seed Composition Using Soybean Fast Neutron Mutants

by Shrikaar Kambhampati, Jose A. Aznar-Moreno, Cooper Hostetler, Tara Caso, Sally R. Bailey, Allen H. Hubbard, Timothy P. Durrett and Doug K. Allen

Metabolites 2020, 10(1), 18; https://doi.org/10.3390/metabo10010018 - 28 Dec 2019

Cited by 28 | Viewed by 3836

Abstract

Protein and oil levels measured at maturity are inversely correlated across soybean lines; however, carbon is in limited supply during maturation resulting in tradeoffs for the production of other reserves including oligosaccharides. During the late stages of seed development, the allocation of carbon [...] Read more.

Protein and oil levels measured at maturity are inversely correlated across soybean lines; however, carbon is in limited supply during maturation resulting in tradeoffs for the production of other reserves including oligosaccharides. During the late stages of seed development, the allocation of carbon for storage reserves changes. Lipid and protein levels decline while concentrations of indigestible raffinose family oligosaccharides (RFOs) increase, leading to a decreased crop value. Since the maternal source of carbon is diminished during seed maturation stages of development, carbon supplied to RFO synthesis likely comes from an internal, turned-over source and may contribute to the reduction in protein and lipid content in mature seeds. In this study, fast neutron (FN) mutagenized soybean populations with deletions in central carbon metabolic genes were examined for trends in oil, protein, sugar, and RFO accumulation leading to an altered final composition. Two lines with concurrent increases in oil and protein, by combined 10%, were identified. A delayed switch in carbon allocation towards RFO biosynthesis resulted in extended lipid accumulation and without compromising protein. Strategies for future soybean improvement using FN resources are described. Full article

(This article belongs to the Special Issue Metabolomic and Flux Analysis in Plants)

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23 pages, 4556 KiB

Open AccessReview

Green and White Asparagus (Asparagus officinalis): A Source of Developmental, Chemical and Urinary Intrigue

by Eirini Pegiou, Roland Mumm, Parag Acharya, Ric C. H. de Vos and Robert D. Hall

Metabolites 2020, 10(1), 17; https://doi.org/10.3390/metabo10010017 - 25 Dec 2019

Cited by 55 | Viewed by 12942

Abstract

Asparagus (Asparagus officinalis) is one of the world’s top 20 vegetable crops. Both green and white shoots (spears) are produced; the latter being harvested before becoming exposed to light. The crop is grown in nearly all areas of the world, with the largest [...] Read more.

Asparagus (Asparagus officinalis) is one of the world’s top 20 vegetable crops. Both green and white shoots (spears) are produced; the latter being harvested before becoming exposed to light. The crop is grown in nearly all areas of the world, with the largest production regions being China, Western Europe, North America and Peru. Successful production demands high farmer input and specific environmental conditions and cultivation practices. Asparagus materials have also been used for centuries as herbal medicine. Despite this widespread cultivation and consumption, we still know relatively little about the biochemistry of this crop and how this relates to the nutritional, flavour, and neutra-pharmaceutical properties of the materials used. To date, no-one has directly compared the contrasting compositions of the green and white crops. In this short review, we have summarised most of the literature to illustrate the chemical richness of the crop and how this might relate to key quality parameters. Asparagus has excellent nutritional properties and its flavour/fragrance is attributed to a set of volatile components including pyrazines and sulphur-containing compounds. More detailed research, however, is needed and we propose that (untargeted) metabolomics should have a more prominent role to play in these investigations. Full article

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18 pages, 2411 KiB

Open AccessArticle

Genome-Scale Metabolic Modeling with Protein Expressions of Normal and Cancerous Colorectal Tissues for Oncogene Inference

by Feng-Sheng Wang, Wu-Hsiung Wu, Wei-Shiang Hsiu, Yan-Jun Liu and Kuan-Wei Chuang

Metabolites 2020, 10(1), 16; https://doi.org/10.3390/metabo10010016 - 25 Dec 2019

Cited by 13 | Viewed by 3324

Abstract

Although cancer has historically been regarded as a cell proliferation disorder, it has recently been considered a metabolic disease. The first discovery of metabolic alterations in cancer cells refers to Otto Warburg’s observations. Cancer metabolism results in alterations in metabolic fluxes that are [...] Read more.

Although cancer has historically been regarded as a cell proliferation disorder, it has recently been considered a metabolic disease. The first discovery of metabolic alterations in cancer cells refers to Otto Warburg’s observations. Cancer metabolism results in alterations in metabolic fluxes that are evident in cancer cells compared with most normal tissue cells. This study applied protein expressions of normal and cancer cells to reconstruct two tissue-specific genome-scale metabolic models. Both models were employed in a tri-level optimization framework to infer oncogenes. Moreover, this study also introduced enzyme pseudo-coding numbers in the gene association expression to avoid performing posterior decision-making that is necessary for the reaction-based method. Colorectal cancer (CRC) was the topic of this case study, and 20 top-ranked oncogenes were determined. Notably, these dysregulated genes were involved in various metabolic subsystems and compartments. We found that the average similarity ratio for each dysregulation is higher than 98%, and the extent of similarity for flux changes is higher than 93%. On the basis of surveys of PubMed and GeneCards, these oncogenes were also investigated in various carcinomas and diseases. Most dysregulated genes connect to catalase that acts as a hub and connects protein signaling pathways, such as those involving TP53, mTOR, AKT1, MAPK1, EGFR, MYC, CDK8, and RAS family. Full article

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14 pages, 508 KiB

Open AccessArticle

The Antimethanogenic Nitrocompounds Can be Cleaved into Nitrite by Rumen Microorganisms: A Comparison of Nitroethane, 2-Nitroethanol, and 2-Nitro-1-propanol

by Zhen-Wei Zhang, Yan-Lu Wang, Wei-Kang Wang, Yong-Yang Chen, Xue-Meng Si, Ya-Jing Wang, Wei Wang, Zhi-Jun Cao, Sheng-Li Li and Hong-Jian Yang

Metabolites 2020, 10(1), 15; https://doi.org/10.3390/metabo10010015 - 25 Dec 2019

Cited by 3 | Viewed by 2436

Abstract

A class of aliphatic short chain nitrocompounds have been reported as being capable of CH₄ reduction both in vitro and in vivo. However, the laboratory evidence associated with the metabolic fate of nitrocompounds in the rumen has not been well documented. The [...] Read more.

A class of aliphatic short chain nitrocompounds have been reported as being capable of CH₄ reduction both in vitro and in vivo. However, the laboratory evidence associated with the metabolic fate of nitrocompounds in the rumen has not been well documented. The present study was conducted to compare in vitro degradation and metabolism of nitroethane (NE), 2-nitroethanol (NEOH), and 2-nitro-1-propanol (NPOH) incubated with mixed rumen microorganisms of dairy cows. After 10 mM supplementation of nitrocompounds, a serious of batch cultures were carried out for 120 h under the presence of two substrates differing in the ratio of maize meal to alfalfa hay (HF, 1:4; LF, 4:1). Compared to the control, methane production was reduced by 59% in NPOH and by >97% in both NE and NEOH, and such antimethanogenic effects were more pronounced in the LF than the HF group. Although NE, NEOH, and NPOH addition did not alter total VFA production, the rumen fermentation pattern shifted toward increasing propionate and butyrate and decreasing acetate production. The kinetic disappearance of each nitrocompound was well fitted to the one-compartment model, and the disappearance rate (k, %/h) of NE was 2.6 to 5.2 times greater than those of NEOH and NPOH. Higher intermediates of nitrite occurred in NEOH in comparison with NPOH and NE while ammonia N production was lowest in NEOH. Consequently, a stepwise accumulation of bacterial crude protein (BCP) in response to the nitrocompound addition was observed in both the HF and LF group. In brief, both NE and NEOH in comparison with NPOH presented greater antimethanogenic activity via the shift of rumen fermentation. In addition, the present study provided the first direct evidence that rumen microbes were able to cleave these nitrocompounds into nitrite, and the subsequent metabolism of nitrite into ammonia N may enhance the growth of rumen microbes or promote microbial activities. Full article

(This article belongs to the Special Issue Metabolomics and Microbiota Metabolism)

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16 pages, 2350 KiB

Open AccessArticle

13C-Metabolic Flux Analysis in Developing Flax (Linum usitatissinum L.) Embryos to Understand Storage Lipid Biosynthesis

by Sébastien Acket, Anthony Degournay, Yannick Rossez, Stéphane Mottelet, Pierre Villon, Adrian Troncoso-Ponce and Brigitte Thomasset

Metabolites 2020, 10(1), 14; https://doi.org/10.3390/metabo10010014 - 24 Dec 2019

Cited by 6 | Viewed by 3571

Abstract

Flax (Linum usitatissinum L.) oil is an important source of α-linolenic (C18:3 ω-3). This polyunsaturated fatty acid is well known for its nutritional role in human and animal diets. Understanding storage lipid biosynthesis in developing flax embryos can lead to an increase [...] Read more.

Flax (Linum usitatissinum L.) oil is an important source of α-linolenic (C18:3 ω-3). This polyunsaturated fatty acid is well known for its nutritional role in human and animal diets. Understanding storage lipid biosynthesis in developing flax embryos can lead to an increase in seed yield via marker-assisted selection. While a tremendous amount of work has been done on different plant species to highlight their metabolism during embryo development, a comprehensive analysis of metabolic flux in flax is still lacking. In this context, we have utilized in vitro cultured developing embryos of flax and determined net fluxes by performing three complementary parallel labeling experiments with 13C-labeled glucose and glutamine. Metabolic fluxes were estimated by computer-aided modeling of the central metabolic network including 11 cofactors of 118 reactions of the central metabolism and 12 pseudo-fluxes. A focus on lipid storage biosynthesis and the associated pathways was done in comparison with rapeseed, arabidopsis, maize and sunflower embryos. In our hands, glucose was determined to be the main source of carbon in flax embryos, leading to the conversion of phosphoenolpyruvate to pyruvate. The oxidative pentose phosphate pathway (OPPP) was identified as the producer of NADPH for fatty acid biosynthesis. Overall, the use of 13C-metabolic flux analysis provided new insights into the flax embryo metabolic processes involved in storage lipid biosynthesis. The elucidation of the metabolic network of this important crop plant reinforces the relevance of the application of this technique to the analysis of complex plant metabolic systems. Full article

(This article belongs to the Special Issue Metabolomic and Flux Analysis in Plants)

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17 pages, 3239 KiB

Open AccessArticle

Generation of a Collision Cross Section Library for Multi-Dimensional Plant Metabolomics Using UHPLC-Trapped Ion Mobility-MS/MS

by Mark Schroeder, Sven W. Meyer, Heino M. Heyman, Aiko Barsch and Lloyd W. Sumner

Metabolites 2020, 10(1), 13; https://doi.org/10.3390/metabo10010013 - 24 Dec 2019

Cited by 55 | Viewed by 7270

Abstract

The utility of metabolomics is well documented; however, its full scientific promise has not yet been realized due to multiple technical challenges. These grand challenges include accurate chemical identification of all observable metabolites and the limiting depth-of-coverage of current metabolomics methods. Here, we [...] Read more.

The utility of metabolomics is well documented; however, its full scientific promise has not yet been realized due to multiple technical challenges. These grand challenges include accurate chemical identification of all observable metabolites and the limiting depth-of-coverage of current metabolomics methods. Here, we report a combinatorial solution to aid in both grand challenges using UHPLC-trapped ion mobility spectrometry coupled to tandem mass spectrometry (UHPLC-TIMS-TOF-MS). TIMS offers additional depth-of-coverage through increased peak capacities realized with the multi-dimensional UHPLC-TIMS separations. Metabolite identification confidence is simultaneously enhanced by incorporating orthogonal collision cross section (CCS) data matching. To facilitate metabolite identifications, we created a CCS library of 146 plant natural products. This library was generated using TIMS with N₂ drift gas to record the ^TIMSCCS_N2 of plant natural products with a high degree of reproducibility; i.e., average RSD = 0.10%. The robustness of ^TIMSCCS_N2 data matching was tested using authentic standards spiked into complex plant extracts, and the precision of CCS measurements were determined to be independent of matrix affects. The utility of the UHPLC-TIMS-TOF-MS/MS in metabolomics was then demonstrated using extracts from the model legume Medicago truncatula and metabolites were confidently identified based on retention time, accurate mass, molecular formula, and CCS. Full article

(This article belongs to the Special Issue Compound Identification of Small Molecules)

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14 pages, 1474 KiB

Open AccessArticle

Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in Salmonella enterica

by Andrew J. Borchert, Jacquelyn M. Walejko, Adrien Le Guennec, Dustin C. Ernst, Arthur S. Edison and Diana M. Downs

Metabolites 2020, 10(1), 12; https://doi.org/10.3390/metabo10010012 - 24 Dec 2019

Cited by 10 | Viewed by 3485

Abstract

In Salmonella enterica, 2-aminoacrylate (2AA) is a reactive enamine intermediate generated during a number of biochemical reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA; EC: 3.5.99.10) is eliminated, 2AA accumulates and inhibits the activity of multiple pyridoxal 5’-phosphate(PLP)-dependent enzymes. In this study, untargeted proton [...] Read more.

In Salmonella enterica, 2-aminoacrylate (2AA) is a reactive enamine intermediate generated during a number of biochemical reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA; EC: 3.5.99.10) is eliminated, 2AA accumulates and inhibits the activity of multiple pyridoxal 5’-phosphate(PLP)-dependent enzymes. In this study, untargeted proton nuclear magnetic resonance (¹H NMR) metabolomics and transcriptomics data were used to uncover the global metabolic response of S. enterica to the accumulation of 2AA. The data showed that elimination of RidA perturbed folate and branched chain amino acid metabolism. Many of the resulting perturbations were consistent with the known effect of 2AA stress, while other results suggested additional potential enzyme targets of 2AA-dependent damage. The majority of transcriptional and metabolic changes appeared to be the consequence of downstream effects on the metabolic network, since they were not directly attributable to a PLP-dependent enzyme. In total, the results highlighted the complexity of changes stemming from multiple perturbations of the metabolic network, and suggested hypotheses that will be valuable in future studies of the RidA paradigm of endogenous 2AA stress. Full article

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