Metabolites

10 pages, 1079 KiB

Open AccessArticle

Quantification of All-Trans Retinoic Acid by Liquid Chromatography–Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes

by Jakob Morgenstern, Thomas Fleming, Elisabeth Kliemank, Maik Brune, Peter Nawroth and Andreas Fischer

Metabolites 2021, 11(1), 60; https://doi.org/10.3390/metabo11010060 - 19 Jan 2021

Cited by 11 | Viewed by 3305

Abstract

Retinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (atRA) is the major occurring metabolite of retinoic acid in humans. This [...] Read more.

Retinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (atRA) is the major occurring metabolite of retinoic acid in humans. This study provides a sensitive and specific liquid chromatography–tandem mass spectrometry approach in order to quantify atRA in human plasma samples. The isolation of atRA by hyperacidified liquid–liquid extraction using hexane and ethyl acetate resulted in a recovery of 89.7 ± 9.2%. The lower limit of detection was 20 pg·mL⁻¹, and 7 point calibration displayed good linearity (R² = 0.994) in the range of 50–3200 pg mL⁻¹. Selectivity was guaranteed by the use of two individual mass transitions (qualifier and quantifier), and precision and accuracy were determined intraday and interday with a coefficient variation of 9.3% (intraday) and 14.0% (interday). Moreover, the method could be used to isolate atRA from hyperlipidemic samples. Applying this method to plasma samples from patients with poorly controlled Type 2 diabetes significantly decreased atRA plasma levels as compared to those of the healthy controls. In addition, atRA concentrations were highly associated with increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) cholesterol levels. Full article

(This article belongs to the Section Advances in Metabolomics)

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13 pages, 761 KiB

Open AccessArticle

Physical Activity-Related Metabolites Are Associated with Mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) Study

by Jun Xu, Guning Liu, Sheila M. Hegde, Priya Palta, Eric Boerwinkle, Kelley P. Gabriel and Bing Yu

Metabolites 2021, 11(1), 59; https://doi.org/10.3390/metabo11010059 - 19 Jan 2021

Cited by 4 | Viewed by 3305

Abstract

Habitual physical activity can diminish the risk of premature death. Identifying a pattern of metabolites related to physical activity may advance our understanding of disease etiology. We quantified 245 serum metabolites in 3802 participants from the Atherosclerosis Risk in Communities (ARIC) study using [...] Read more.

Habitual physical activity can diminish the risk of premature death. Identifying a pattern of metabolites related to physical activity may advance our understanding of disease etiology. We quantified 245 serum metabolites in 3802 participants from the Atherosclerosis Risk in Communities (ARIC) study using chromatography–mass spectrometry. We regressed self-reported moderate-to-vigorous intensity leisure-time physical activity (LTPA) against each metabolite, adjusting for traditional risk factors. A standardized metabolite risk score (MRS) was constructed to examine its association with all-cause mortality using the Cox proportional hazard model. We identified 10 metabolites associated with LTPA (p < 2.04 × 10⁻⁴) and established that an increase of one unit of the metabolic equivalent of task-hours per week (MET·hr·wk⁻¹) in LTPA was associated with a 0.012 SD increase in MRS. During a median of 27.5 years of follow-up, we observed 1928 deaths. One SD increase of MRS was associated with a 10% lower risk of death (HR = 0.90, 95% CI: 0.85–0.95). The highest vs. the lowest MRS quintile rank was associated with a 22% reduced risk of death (HR = 0.78, 95% CI: 0.62–0.94). The effects were consistent across race and sex groups. In summary, we identified a set of metabolites associated with LTPA and an MRS associated with a lower risk of death. Our study provides novel insights into the potential mechanisms underlying the health impacts of physical activity. Full article

(This article belongs to the Special Issue Metabolomics and Its Application in Human Diseases Volume 2)

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17 pages, 3170 KiB

Open AccessEditor’s ChoiceArticle

Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E₂ Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes

by Michael D. Schaid, Yanlong Zhu, Nicole E. Richardson, Chinmai Patibandla, Irene M. Ong, Rachel J. Fenske, Joshua C. Neuman, Erin Guthery, Austin Reuter, Harpreet K. Sandhu, Miles H. Fuller, Elizabeth D. Cox, Dawn B. Davis, Brian T. Layden, Allan R. Brasier, Dudley W. Lamming, Ying Ge and Michelle E. Kimple

Metabolites 2021, 11(1), 58; https://doi.org/10.3390/metabo11010058 - 16 Jan 2021

Cited by 17 | Viewed by 4765

Abstract

The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 [...] Read more.

The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 ligand is the arachidonic acid metabolite prostaglandin E₂ (PGE₂). Expression of the pancreatic islet EP3 and PGE₂ synthetic enzymes and/or PGE₂ excretion itself have all been shown to be upregulated in primary mouse and human islets isolated from animals or human organ donors with established T2D compared to nondiabetic controls. In this study, we took advantage of a rare and fleeting phenotype in which a subset of Black and Tan BRachyury (BTBR) mice homozygous for the Leptin^ob/ob mutation—a strong genetic model of T2D—were entirely protected from fasting hyperglycemia even with equal obesity and insulin resistance as their hyperglycemic littermates. Utilizing this model, we found numerous alterations in full-body metabolic parameters in T2D-protected mice (e.g., gut microbiome composition, circulating pancreatic and incretin hormones, and markers of systemic inflammation) that correlate with improvements in EP3-mediated β-cell dysfunction. Full article

(This article belongs to the Special Issue Islet Inflammation and Metabolic Homeostasis)

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13 pages, 2229 KiB

Open AccessArticle

Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using N^α-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)

by Taiji Yamamoto, Keisuke Yaku and Takashi Nakagawa

Metabolites 2021, 11(1), 57; https://doi.org/10.3390/metabo11010057 - 15 Jan 2021

Cited by 11 | Viewed by 3945

Abstract

d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino [...] Read more.

d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino acid enantiomers in cells and tissues. Various quantification methods have been developed for measurements of chiral amino acids. However, each method has advantages and disadvantages. Additionally, measuring the amino acid enantiomers in crude biological samples requires a higher selectivity. In this study, we developed a quantification method for amino acid enantiomers using derivatization with N^α-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA) followed by liquid chromatography–tandem mass spectrometry (LC/MS/MS) with a conventional reversed-phase column. We simultaneously identified 10 chiral amino acids. Furthermore, we applied this method to investigate murine tissue samples and examined the effect of aging on the amino acid levels in aged brain regions. We found that aging decreased the levels of both d-serine and d-aspartate in the hippocampus. In addition, d-Phenylalanine in the thalamus significantly increased with age. In conclusion, our method is suitable for the quantification of the d-amino acids in crude biological samples and may contribute to elucidating the biological roles of chiral amino acids. Full article

(This article belongs to the Section Animal Metabolism)

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12 pages, 2180 KiB

Open AccessArticle

Exploring the Characteristic Aroma of Beef from Japanese Black Cattle (Japanese Wagyu) via Sensory Evaluation and Gas Chromatography-Olfactometry

by Shuji Ueda, Minoru Yamanoue, Yasuhito Sirai and Eiji Iwamoto

Metabolites 2021, 11(1), 56; https://doi.org/10.3390/metabo11010056 - 15 Jan 2021

Cited by 22 | Viewed by 4890

Abstract

Beef from Japanese Black cattle (Japanese Wagyu) is renowned for its flavor characteristics. To clarify the key metabolites contributing to this rich and sweet aroma of beef, an omics analysis combined with GC-olfactometry (GC-O) and metabolomics analysis with gas chromatography–mass spectrometry (GC-MS) were [...] Read more.

Beef from Japanese Black cattle (Japanese Wagyu) is renowned for its flavor characteristics. To clarify the key metabolites contributing to this rich and sweet aroma of beef, an omics analysis combined with GC-olfactometry (GC-O) and metabolomics analysis with gas chromatography–mass spectrometry (GC-MS) were applied. GC-O analysis identified 39 odor-active odorants from the volatile fraction of boiled beef distilled by solvent-assisted flavor evaporation. Eight odorants predicted to contribute to Wagyu beef aroma were compared between Japanese Black cattle and Holstein cattle using a stable isotope dilution assay with GC–tandem quadrupole mass spectrometry. By correlating the sensory evaluation values of retronasal aroma, γ-hexalactone, γ-decalactone, and γ-undecalactone showed a high correlation with the Wagyu beef aroma. Metabolomics data revealed a high correlation between the amounts of odorants and multiple metabolites, such as glutamine, decanoic acid, lactic acid, and phosphoric acid. These results provide useful information for assessing the aroma and quality of beef. Full article

(This article belongs to the Special Issue Metabolomic Applications in Animal Science Volume 2)

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15 pages, 1183 KiB

Open AccessFeature PaperReview

Linking Gut Microbiome and Lipid Metabolism: Moving beyond Associations

by Santosh Lamichhane, Partho Sen, Marina Amaral Alves, Henrique C. Ribeiro, Peppi Raunioniemi, Tuulia Hyötyläinen and Matej Orešič

Metabolites 2021, 11(1), 55; https://doi.org/10.3390/metabo11010055 - 15 Jan 2021

Cited by 61 | Viewed by 9281

Abstract

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, [...] Read more.

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, only recently, several studies have shown how microbial lipids alter intestinal and circulating lipid concentrations in the host, thus impacting human lipid homeostasis. There is emerging evidence that gut microbial communities play a particularly significant role in the regulation of host cholesterol and sphingolipid homeostasis. Here, we review and discuss recent research focusing on microbe-host-lipid co-metabolism. We also discuss the interplay of human gut microbiota and molecular lipids entering host systemic circulation, and its role in health and disease. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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19 pages, 2948 KiB

Open AccessArticle

Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity

by Benjamin Buchard, Camille Teilhet, Natali Abeywickrama Samarakoon, Sylvie Massoulier, Juliette Joubert-Zakeyh, Corinne Blouin, Christelle Reynes, Robert Sabatier, Anne-Sophie Biesse-Martin, Marie-Paule Vasson, Armando Abergel and Aicha Demidem

Metabolites 2021, 11(1), 54; https://doi.org/10.3390/metabo11010054 - 14 Jan 2021

Cited by 15 | Viewed by 2842

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to [...] Read more.

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using ¹H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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19 pages, 1281 KiB

Open AccessArticle

Comprehensive Comparative Analysis of Local False Discovery Rate Control Methods

by Shin June Kim, Youngjae Oh and Jaesik Jeong

Metabolites 2021, 11(1), 53; https://doi.org/10.3390/metabo11010053 - 14 Jan 2021

Cited by 1 | Viewed by 2349

Abstract

Due to the advance in technology, the type of data is getting more complicated and large-scale. To analyze such complex data, more advanced technique is required. In case of omics data from two different groups, it is interesting to find significant biomarkers between [...] Read more.

Due to the advance in technology, the type of data is getting more complicated and large-scale. To analyze such complex data, more advanced technique is required. In case of omics data from two different groups, it is interesting to find significant biomarkers between two groups while controlling error rate such as false discovery rate (FDR). Over the last few decades, a lot of methods that control local false discovery rate have been developed, ranging from one-dimensional to k-dimensional FDR procedure. For comparison study, we select three of them, which have unique and significant properties: Efron’s approach, Ploner’s approach, and Kim’s approach in chronological order. The first approach is one-dimensional approach while the other two are two-dimensional ones. Furthermore, we consider two more variants of Ploner’s approach. We compare the performance of those methods on both simulated and real data. Full article

(This article belongs to the Special Issue Data Science in Metabolomics)

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19 pages, 1685 KiB

Open AccessReview

Beyond Proteostasis: Lipid Metabolism as a New Player in ER Homeostasis

by Jiaming Xu and Stefan Taubert

Metabolites 2021, 11(1), 52; https://doi.org/10.3390/metabo11010052 - 14 Jan 2021

Cited by 26 | Viewed by 5266

Abstract

Biological membranes are not only essential barriers that separate cellular and subcellular structures, but also perform other critical functions such as the initiation and propagation of intra- and intercellular signals. Each membrane-delineated organelle has a tightly regulated and custom-made membrane lipid composition that [...] Read more.

Biological membranes are not only essential barriers that separate cellular and subcellular structures, but also perform other critical functions such as the initiation and propagation of intra- and intercellular signals. Each membrane-delineated organelle has a tightly regulated and custom-made membrane lipid composition that is critical for its normal function. The endoplasmic reticulum (ER) consists of a dynamic membrane network that is required for the synthesis and modification of proteins and lipids. The accumulation of unfolded proteins in the ER lumen activates an adaptive stress response known as the unfolded protein response (UPR-ER). Interestingly, recent findings show that lipid perturbation is also a direct activator of the UPR-ER, independent of protein misfolding. Here, we review proteostasis-independent UPR-ER activation in the genetically tractable model organism Caenorhabditis elegans. We review the current knowledge on the membrane lipid composition of the ER, its impact on organelle function and UPR-ER activation, and its potential role in human metabolic diseases. Further, we summarize the bi-directional interplay between lipid metabolism and the UPR-ER. We discuss recent progress identifying the different respective mechanisms by which disturbed proteostasis and lipid bilayer stress activate the UPR-ER. Finally, we consider how genetic and metabolic disturbances may disrupt ER homeostasis and activate the UPR and discuss how using -omics-type analyses will lead to more comprehensive insights into these processes. Full article

(This article belongs to the Special Issue Caenorhabditis elegans Applied to Metabolism Research)

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21 pages, 1982 KiB

Open AccessEditor’s ChoiceReview

L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

by Marc R. McCann, Mery Vet George De la Rosa, Gus R. Rosania and Kathleen A. Stringer

Metabolites 2021, 11(1), 51; https://doi.org/10.3390/metabo11010051 - 14 Jan 2021

Cited by 160 | Viewed by 11224

Abstract

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or [...] Read more.

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets. Full article

(This article belongs to the Special Issue Mitochondrial Metabolism and Bioenergetics)

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14 pages, 2578 KiB

Open AccessArticle

In Vivo Metabolism of [1,6-¹³C₂]Glucose Reveals Distinct Neuroenergetic Functionality between Mouse Hippocampus and Hypothalamus

by Antoine Cherix, Rajesh Sonti, Bernard Lanz and Hongxia Lei

Metabolites 2021, 11(1), 50; https://doi.org/10.3390/metabo11010050 - 12 Jan 2021

Cited by 3 | Viewed by 2577

Abstract

Glucose is a major energy fuel for the brain, however, less is known about specificities of its metabolism in distinct cerebral areas. Here we examined the regional differences in glucose utilization between the hypothalamus and hippocampus using in vivo indirect ¹³C magnetic [...] Read more.

Glucose is a major energy fuel for the brain, however, less is known about specificities of its metabolism in distinct cerebral areas. Here we examined the regional differences in glucose utilization between the hypothalamus and hippocampus using in vivo indirect ¹³C magnetic resonance spectroscopy (¹H-[¹³C]-MRS) upon infusion of [1,6-¹³C₂]glucose. Using a metabolic flux analysis with a 1-compartment mathematical model of brain metabolism, we report that compared to hippocampus, hypothalamus shows higher levels of aerobic glycolysis associated with a marked gamma-aminobutyric acid-ergic (GABAergic) and astrocytic metabolic dependence. In addition, our analysis suggests a higher rate of ATP production in hypothalamus that is accompanied by an excess of cytosolic nicotinamide adenine dinucleotide (NADH) production that does not fuel mitochondria via the malate-aspartate shuttle (MAS). In conclusion, our results reveal significant metabolic differences, which might be attributable to respective cell populations or functional features of both structures. Full article

(This article belongs to the Special Issue Computational Biology for Metabolic Modelling)

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11 pages, 999 KiB

Open AccessReview

Trimethylornithine Membrane Lipids: Discovered in Planctomycetes and Identified in Diverse Environments

by Eli K. Moore

Metabolites 2021, 11(1), 49; https://doi.org/10.3390/metabo11010049 - 12 Jan 2021

Cited by 6 | Viewed by 2764

Abstract

Intact polar membrane lipids (IPLs) are the building blocks of all cell membranes. There is a wide range of phosphorus-free IPL structures, including amino acid containing IPLs, that can be taxonomically specific. Trimethylornithine membrane lipids (TMOs) were discovered in northern wetland Planctomycete species [...] Read more.

Intact polar membrane lipids (IPLs) are the building blocks of all cell membranes. There is a wide range of phosphorus-free IPL structures, including amino acid containing IPLs, that can be taxonomically specific. Trimethylornithine membrane lipids (TMOs) were discovered in northern wetland Planctomycete species that were isolated and described in the last decade. The trimethylated terminal nitrogen moiety of the ornithine amino acid in the TMO structure gives the lipid a charged polar head group, similar to certain phospholipids. Since their discovery, TMOs have been identified in various other recently described northern latitude Planctomycete species, and in diverse environments including tundra soil, a boreal eutrophic lake, meso-oligotrophic lakes, and hot springs. The majority of environments or enrichment cultures in which TMOs have been observed include predominately heterotrophic microbial communities involved in the degradation of recalcitrant material and/or low oxygen methanogenic conditions at primarily northern latitudes. Other ecosystems occupied with microbial communities that possess similar metabolic pathways, such as tropical peatlands or coastal salt marshes, may include TMO producing Planctomycetes as well, further allowing these lipids to potentially be used to understand microbial community responses to environmental change in a wide range of systems. The occurrence of TMOs in hot springs indicates that these unique lipids could have broad environmental distribution with different specialized functions. Opportunities also exist to investigate the application of TMOs in microbiome studies, including forensic necrobiomes. Further environmental and microbiome lipidomics research involving TMOs will help reveal the evolution, functions, and applications of these unique membrane lipids. Full article

(This article belongs to the Special Issue Metabolomics of Fatty Acyl Esters of Hydroxy Fatty Acids: Three Diverse Lipid Families)

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15 pages, 2939 KiB

Open AccessArticle

Diverse Taxonomies for Diverse Chemistries: Enhanced Representation of Natural Product Metabolism in UniProtKB

by Marc Feuermann, Emmanuel Boutet, Anne Morgat, Kristian B. Axelsen, Parit Bansal, Jerven Bolleman, Edouard de Castro, Elisabeth Coudert, Elisabeth Gasteiger, Sébastien Géhant, Damien Lieberherr, Thierry Lombardot, Teresa B. Neto, Ivo Pedruzzi, Sylvain Poux, Monica Pozzato, Nicole Redaschi, Alan Bridge and on behalf of the UniProt Consortium

Metabolites 2021, 11(1), 48; https://doi.org/10.3390/metabo11010048 - 12 Jan 2021

Cited by 3 | Viewed by 4095

Abstract

The UniProt Knowledgebase UniProtKB is a comprehensive, high-quality, and freely accessible resource of protein sequences and functional annotation that covers genomes and proteomes from tens of thousands of taxa, including a broad range of plants and microorganisms producing natural products of medical, nutritional, [...] Read more.

The UniProt Knowledgebase UniProtKB is a comprehensive, high-quality, and freely accessible resource of protein sequences and functional annotation that covers genomes and proteomes from tens of thousands of taxa, including a broad range of plants and microorganisms producing natural products of medical, nutritional, and agronomical interest. Here we describe work that enhances the utility of UniProtKB as a support for both the study of natural products and for their discovery. The foundation of this work is an improved representation of natural product metabolism in UniProtKB using Rhea, an expert-curated knowledgebase of biochemical reactions, that is built on the ChEBI (Chemical Entities of Biological Interest) ontology of small molecules. Knowledge of natural products and precursors is captured in ChEBI, enzyme-catalyzed reactions in Rhea, and enzymes in UniProtKB/Swiss-Prot, thereby linking chemical structure data directly to protein knowledge. We provide a practical demonstration of how users can search UniProtKB for protein knowledge relevant to natural products through interactive or programmatic queries using metabolite names and synonyms, chemical identifiers, chemical classes, and chemical structures and show how to federate UniProtKB with other data and knowledge resources and tools using semantic web technologies such as RDF and SPARQL. All UniProtKB data are freely available for download in a broad range of formats for users to further mine or exploit as an annotation source, to enrich other natural product datasets and databases. Full article

(This article belongs to the Special Issue Computational Methods for Secondary Metabolite Discovery)

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18 pages, 2714 KiB

Open AccessArticle

Analytical Methods for Quantification and Identification of Intact Glucosinolates in Arabidopsis Roots Using LC-QqQ(LIT)-MS/MS

by Kourosh Hooshmand and Inge S. Fomsgaard

Metabolites 2021, 11(1), 47; https://doi.org/10.3390/metabo11010047 - 11 Jan 2021

Cited by 12 | Viewed by 4281

Abstract

Glucosinolates are biologically active secondary metabolites in Brassicaceae plants that play a critical role in positive and negative interactions between plants and root-associated microbial communities. The aim of this study was to develop a reversed-phase liquid chromatography method to quantify and identify intact [...] Read more.

Glucosinolates are biologically active secondary metabolites in Brassicaceae plants that play a critical role in positive and negative interactions between plants and root-associated microbial communities. The aim of this study was to develop a reversed-phase liquid chromatography method to quantify and identify intact glucosinolates in the root of Arabidopsis thaliana (Arabidopsis) grown in non-sterile natural soil by using liquid chromatography-hybrid triple quadruple-linear ion trap (LC-QqQ(LIT)) mass spectrometry. The Synergi Fusion C18-based column was found to be effective for sufficient retention and separation of nine intact glucosinolates without the need for time-consuming desulfation or ion-pairing steps. Method validation results showed satisfactory inter-day and intra-day precision for all glucosinolates except for 4-hydroxyglucobrassicin. Good inter-day and intra-day accuracy and recovery results were observed for glucoiberin, gluconapin, glucobrassicin, 4-methoxyglucobrassicin and neoglucobrassicin. However, for 4-hydroxyglucobrassicin, glucoraphanin and glucoerucin corrections to quantification results might be necessary since the recovery and accuracy results were not optimal. Matrix effects were shown to have a negligible effect on the ionization of all target analytes. The established liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was applied to quantify target intact glucosinolates in Arabidopsis root crude extract of four different wild-type accessions where differences in terms of concentration and composition of intact glucosinolates were observed. Employment of sensitive and selective precursor ion survey scan of m/z 97 in combination with the information-dependent acquisition (IDA) of the enhanced product ion (EPI) dependent scan (Prec97-IDA-EPI) using LC-QqQ(LIT) provided high confidence in structural characterization of diverse intact glucosinolate profiles in complex Arabidopsis root crude extract. Full article

(This article belongs to the Section Metabolomic Profiling Technology)

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13 pages, 2864 KiB

Open AccessArticle

Free Saturated Oxo Fatty Acids (SOFAs) and Ricinoleic Acid in Milk Determined by a Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS) Method

by Maroula G. Kokotou, Charikleia S. Batsika, Christiana Mantzourani and George Kokotos

Metabolites 2021, 11(1), 46; https://doi.org/10.3390/metabo11010046 - 11 Jan 2021

Cited by 10 | Viewed by 3380

Abstract

Oxidized saturated fatty acids, containing a hydroxyl or an oxo functionality, have attracted little attention so far. Recent studies have shown that saturated hydroxy fatty acids, which exhibit cancer cell growth inhibition and may suppress β-cell apoptosis, are present in milk. Herein, we [...] Read more.

Oxidized saturated fatty acids, containing a hydroxyl or an oxo functionality, have attracted little attention so far. Recent studies have shown that saturated hydroxy fatty acids, which exhibit cancer cell growth inhibition and may suppress β-cell apoptosis, are present in milk. Herein, we present the application of a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the detection and quantification of various saturated oxo fatty acids (SOFAs) previously unrecognized in milk. This robust and rapid analytical method, which involves simple sample preparation and a single 10-min run, revealed the presence of families of oxostearic acids (OSAs) and oxopalmitic acids (OPAs) in milk. 8OSA, 9OSA, 7OSA, 10OSA and 10OPA were found to be the most abundant SOFAs in both cow and goat milk. Higher contents of SOFAs were found in cow milk in comparison to goat milk. Together with SOFAs, ricinoleic acid, which is isobaric to OSA, was detected and quantified in all milk samples, following a “suspect” HRMS analysis approach. This unique natural fatty acid, which is the main component (>90%) of castor oil triglycerides, was estimated at mean content values of 534.3 ± 6.0 μg/mL and 460 ± 8.1 μg/mL in cow and goat milk samples, respectively. Full article

(This article belongs to the Special Issue Mass Spectrometry-Based Lipidomics)

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15 pages, 4989 KiB

Open AccessEditor’s ChoiceArticle

Tissue-Specific ¹H-NMR Metabolomic Profiling in Mice with Adenine-Induced Chronic Kidney Disease

by Ram B. Khattri, Trace Thome and Terence E. Ryan

Metabolites 2021, 11(1), 45; https://doi.org/10.3390/metabo11010045 - 10 Jan 2021

Cited by 24 | Viewed by 4986

Abstract

Chronic kidney disease (CKD) results in the impaired filtration of metabolites, which may be toxic or harmful to organs/tissues. The objective of this study was to perform unbiased ¹H nuclear magnetic resonance (NMR)-based metabolomics profiling of tissues from mice with CKD. Five-month-old [...] Read more.

Chronic kidney disease (CKD) results in the impaired filtration of metabolites, which may be toxic or harmful to organs/tissues. The objective of this study was to perform unbiased ¹H nuclear magnetic resonance (NMR)-based metabolomics profiling of tissues from mice with CKD. Five-month-old male C57BL6J mice were placed on either a casein control diet or adenine-supplemented diet to induce CKD for 24 weeks. CKD was confirmed by significant increases in blood urea nitrogen (24.1 ± 7.7 vs. 105.3 ± 18.3 mg/dL, p < 0.0001) in adenine-fed mice. Following this chronic adenine diet, the kidney, heart, liver, and quadriceps muscles were rapidly dissected; snap-frozen in liquid nitrogen; and the metabolites were extracted. Metabolomic profiling coupled with multivariate analyses confirm clear separation in both aqueous and organic phases between control and CKD mice. Severe energetic stress and apparent impaired mitochondrial metabolism were observed in CKD kidneys evidenced by the depletion of ATP and NAD⁺, along with significant alterations in tricarboxylic acid (TCA) cycle intermediates. Altered amino acid metabolism was observed in all tissues, although significant differences in specific amino acids varied across tissue types. Taken together, this study provides a metabolomics fingerprint of multiple tissues from mice with and without severe CKD induced by chronic adenine feeding. Full article

(This article belongs to the Special Issue Metabolomics in Kidney Disease)

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14 pages, 2833 KiB

Open AccessArticle

Comprehensive Meta-Analysis of COVID-19 Global Metabolomics Datasets

by Zhiqiang Pang, Guangyan Zhou, Jasmine Chong and Jianguo Xia

Metabolites 2021, 11(1), 44; https://doi.org/10.3390/metabo11010044 - 9 Jan 2021

Cited by 70 | Viewed by 13600

Abstract

The novel coronavirus SARS-CoV-2 has spread across the world since 2019, causing a global pandemic. The pathogenesis of the viral infection and the associated clinical presentations depend primarily on host factors such as age and immunity, rather than the viral load or its [...] Read more.

The novel coronavirus SARS-CoV-2 has spread across the world since 2019, causing a global pandemic. The pathogenesis of the viral infection and the associated clinical presentations depend primarily on host factors such as age and immunity, rather than the viral load or its genetic variations. A growing number of omics studies have been conducted to characterize the host immune and metabolic responses underlying the disease progression. Meta-analyses of these datasets have great potential to identify robust molecular signatures to inform clinical care and to facilitate therapeutics development. In this study, we performed a comprehensive meta-analysis of publicly available global metabolomics datasets obtained from three countries (United States, China and Brazil). To overcome high heterogeneity inherent in these datasets, we have (a) implemented a computational pipeline to perform consistent raw spectra processing; (b) conducted meta-analyses at pathway levels instead of individual feature levels; and (c) performed visual data mining on consistent patterns of change between disease severities for individual studies. Our analyses have yielded several key metabolic signatures characterizing disease progression and clinical outcomes. Their biological interpretations were discussed within the context of the current literature. To the best of our knowledge, this is the first comprehensive meta-analysis of global metabolomics datasets of COVID-19. Full article

(This article belongs to the Special Issue Systematic Reviews and Meta-Analyses (SR-MA) of Metabolites and Disease Risk)

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15 pages, 745 KiB

Open AccessArticle

Molecular Differences Based on Erythrocyte Fatty Acid Profile to Personalize Dietary Strategies between Adults and Children with Obesity

by Iker Jauregibeitia, Kevin Portune, Sonia Gaztambide, Itxaso Rica, Itziar Tueros, Olaia Velasco, Gema Grau, Alicia Martín, Luis Castaño, Anna Vita Larocca, Federica Di Nolfo, Carla Ferreri and Sara Arranz

Metabolites 2021, 11(1), 43; https://doi.org/10.3390/metabo11010043 - 8 Jan 2021

Cited by 10 | Viewed by 3359

Abstract

As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study [...] Read more.

As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study aimed to determine the fatty acid (FA) profile of red blood cell (RBC) membranes, together with the evaluation of their dietary intake and biochemical parameters, of children and adults with obesity. An observational study was carried out on 196 children (113 with normal weight and 83 with obesity) and 91 adults (30 with normal weight and 61 with obesity). Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ). Children with obesity presented higher levels of ω-6 polyunsaturated FAs (mainly linoleic acid, p = 0.01) and lower values of ω-3 FAs (mainly DHA, p < 0.001) compared with adults. Regarding blood biochemical parameters, children with obesity presented lower levels of glucose, LDL cholesterol, and alanine aminotransferase compared with adults with obesity. These lipidomic differences could be considered to provide specific nutritional recommendations for different age groups, based on an adequate fat intake. Full article

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

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16 pages, 3127 KiB

Open AccessArticle

Untargeted Metabolomics Analysis Using FTIR and UHPLC-Q-Orbitrap HRMS of Two Curculigo Species and Evaluation of Their Antioxidant and α-Glucosidase Inhibitory Activities

by Abdul Halim Umar, Diah Ratnadewi, Mohamad Rafi and Yohana Caecilia Sulistyaningsih

Metabolites 2021, 11(1), 42; https://doi.org/10.3390/metabo11010042 - 8 Jan 2021

Cited by 32 | Viewed by 4469

Abstract

Curculigo orchioides and C. latifolia have been used as traditional medicines such as antidiabetic and anticancer. This study measured the total phenolics and flavonoid contents as well as analyzed the functional groups and chemical compounds using Fourier-transform infrared (FTIR) spectra and UHPLC-Q-Orbitrap-HRMS profiling [...] Read more.

Curculigo orchioides and C. latifolia have been used as traditional medicines such as antidiabetic and anticancer. This study measured the total phenolics and flavonoid contents as well as analyzed the functional groups and chemical compounds using Fourier-transform infrared (FTIR) spectra and UHPLC-Q-Orbitrap-HRMS profiling for the discrimination of plant parts, geographical origin, and compounds that presumably have a significant contribution as antioxidant and α-glucosidase inhibitors on both plants. The total phenolics and flavonoids contents in Curculigo species varied from 142.09 to 452.47 mg gallic acid equivalent (GAE/g) and from 0.82 to 5.44 mg quercetin equivalent (QE/g), respectively. The lowest IC₅₀ for antioxidant and α-glucosidase inhibitory activities is presented by C. latifolia from a higher altitude region. Principal component analysis (PCA) from FTIR and UHPLC-Q-Orbitrap-HRMS data could discriminate the plant parts and geographical origin. Partial least squares (PLS) analysis has identified several functional groups, such as O–H, C–H, C=O, C–C, C–O, and chemical compounds, unknown-185 and unknown-85, that are most likely to contribute to the antioxidant and α-glucosidase inhibitory activities. Full article

(This article belongs to the Special Issue Plant and Derived Natural Product Metabolomics)

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22 pages, 2092 KiB

Open AccessReview

Bioactive Ether Lipids: Primordial Modulators of Cellular Signaling

by Nikhil Rangholia, Tina M. Leisner and Stephen P. Holly

Metabolites 2021, 11(1), 41; https://doi.org/10.3390/metabo11010041 - 8 Jan 2021

Cited by 27 | Viewed by 5150

Abstract

The primacy of lipids as essential components of cellular membranes is conserved across taxonomic domains. In addition to this crucial role as a semi-permeable barrier, lipids are also increasingly recognized as important signaling molecules with diverse functional mechanisms ranging from cell surface receptor [...] Read more.

The primacy of lipids as essential components of cellular membranes is conserved across taxonomic domains. In addition to this crucial role as a semi-permeable barrier, lipids are also increasingly recognized as important signaling molecules with diverse functional mechanisms ranging from cell surface receptor binding to the intracellular regulation of enzymatic cascades. In this review, we focus on ether lipids, an ancient family of lipids having ether-linked structures that chemically differ from their more prevalent acyl relatives. In particular, we examine ether lipid biosynthesis in the peroxisome of mammalian cells, the roles of selected glycerolipids and glycerophospholipids in signal transduction in both prokaryotes and eukaryotes, and finally, the potential therapeutic contributions of synthetic ether lipids to the treatment of cancer. Full article

(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism)

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15 pages, 1829 KiB

Open AccessArticle

HPLC-HRMS Global Metabolomics Approach for the Diagnosis of “Olive Quick Decline Syndrome” Markers in Olive Trees Leaves

by Alberto Asteggiano, Pietro Franceschi, Michael Zorzi, Riccardo Aigotti, Federica Dal Bello, Francesca Baldassarre, Francesco Lops, Antonia Carlucci, Claudio Medana and Giuseppe Ciccarella

Metabolites 2021, 11(1), 40; https://doi.org/10.3390/metabo11010040 - 8 Jan 2021

Cited by 8 | Viewed by 3133

Abstract

Olive quick decline syndrome (OQDS) is a multifactorial disease affecting olive plants. The onset of this economically devastating disease has been associated with a Gram-negative plant pathogen called Xylella fastidiosa (Xf). Liquid chromatography separation coupled to high-resolution mass spectrometry detection is one the [...] Read more.

Olive quick decline syndrome (OQDS) is a multifactorial disease affecting olive plants. The onset of this economically devastating disease has been associated with a Gram-negative plant pathogen called Xylella fastidiosa (Xf). Liquid chromatography separation coupled to high-resolution mass spectrometry detection is one the most widely applied technologies in metabolomics, as it provides a blend of rapid, sensitive, and selective qualitative and quantitative analyses with the ability to identify metabolites. The purpose of this work is the development of a global metabolomics mass spectrometry assay able to identify OQDS molecular markers that could discriminate between healthy (HP) and infected (OP) olive tree leaves. Results obtained via multivariate analysis through an HPLC-ESI HRMS platform (LTQ-Orbitrap from Thermo Scientific) show a clear separation between HP and OP samples. Among the differentially expressed metabolites, 18 different organic compounds highly expressed in the OP group were annotated; results obtained by this metabolomic approach could be used as a fast and reliable method for the biochemical characterization of OQDS and to develop targeted MS approaches for OQDS detection by foliage analysis. Full article

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

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16 pages, 1597 KiB

Open AccessArticle

Comparison of Regular, Pure Shift, and Fast 2D NMR Experiments for Determination of the Geographical Origin of Walnuts

by Stephanie Watermann, Caroline Schmitt, Tobias Schneider and Thomas Hackl

Metabolites 2021, 11(1), 39; https://doi.org/10.3390/metabo11010039 - 8 Jan 2021

Cited by 11 | Viewed by 3101

Abstract

¹H NMR spectroscopy, in combination with chemometric methods, was used to analyze the methanol/acetonitrile (1:1) extract of walnut (Juglans Regia L.) regarding the geographical origin of 128 authentic samples from different countries (France, Germany, China) and harvest years (2016–2019). Due to [...] Read more.

¹H NMR spectroscopy, in combination with chemometric methods, was used to analyze the methanol/acetonitrile (1:1) extract of walnut (Juglans Regia L.) regarding the geographical origin of 128 authentic samples from different countries (France, Germany, China) and harvest years (2016–2019). Due to the large number of different metabolites within the acetonitrile/methanol extract, the one-dimensional (1D) ¹H NOESY (nuclear Overhauser effect spectroscopy) spectra suffer from strongly overlapping signals. The identification of specific metabolites and statistical analysis are complicated. The use of pure shift ¹H NMR spectra such as PSYCHE (pure shift yielded by chirp excitation) or two-dimensional ASAP-HSQC (acceleration by sharing adjacent polarization-heteronuclear single quantum correlation) spectra for multivariate analysis to determine the geographical origin of foods may be a promising method. Different types of NMR spectra (1D ¹H NOESY, PSYCHE, and ASAP-HSQC) were acquired for each of the 128 walnut samples and the results of the statistical analysis were compared. A support vector machine classifier was applied for differentiation of samples from Germany/China, France/Germany, and France/China. The models obtained by conduction of a repeated nested cross-validation showed accuracies from 58.9% (±1.3%) to 95.9% (±0.8%). The potential of the ¹H-¹³C HSQC as a 2D NMR experiment for metabolomics studies was shown. Full article

(This article belongs to the Special Issue NMR-Based Metabolomics of Food)

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13 pages, 2774 KiB

Open AccessArticle

Sampling Method Affects HR-MAS NMR Spectra of Healthy Caprine Brain Biopsies

by Annakatrin Häni, Gaëlle Diserens, Anna Oevermann, Peter Vermathen and Christina Precht

Metabolites 2021, 11(1), 38; https://doi.org/10.3390/metabo11010038 - 6 Jan 2021

Cited by 2 | Viewed by 1902

Abstract

The metabolic profiling of tissue biopsies using high-resolution–magic angle spinning (HR-MAS) ¹H nuclear magnetic resonance (NMR) spectroscopy may be influenced by experimental factors such as the sampling method. Therefore, we compared the effects of two different sampling methods on the metabolome of [...] Read more.

The metabolic profiling of tissue biopsies using high-resolution–magic angle spinning (HR-MAS) ¹H nuclear magnetic resonance (NMR) spectroscopy may be influenced by experimental factors such as the sampling method. Therefore, we compared the effects of two different sampling methods on the metabolome of brain tissue obtained from the brainstem and thalamus of healthy goats by ¹H HR-MAS NMR spectroscopy—in vivo-harvested biopsy by a minimally invasive stereotactic approach compared with postmortem-harvested sample by dissection with a scalpel. Lactate and creatine were elevated, and choline-containing compounds were altered in the postmortem compared to the in vivo-harvested samples, demonstrating rapid changes most likely due to sample ischemia. In addition, in the brainstem samples acetate and inositols, and in the thalamus samples ƴ-aminobutyric acid, were relatively increased postmortem, demonstrating regional differences in tissue degradation. In conclusion, in vivo-harvested brain biopsies show different metabolic alterations compared to postmortem-harvested samples, reflecting less tissue degradation. Sampling method and brain region should be taken into account in the analysis of metabolic profiles. To be as close as possible to the actual situation in the living individual, it is desirable to use brain samples obtained by stereotactic biopsy whenever possible. Full article

(This article belongs to the Section Metabolomic Profiling Technology)

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19 pages, 1120 KiB

Open AccessReview

Involvements of Hyperhomocysteinemia in Neurological Disorders

by Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Salvatore Cuzzocrea, Rosanna Di Paola and Daniela Impellizzeri

Metabolites 2021, 11(1), 37; https://doi.org/10.3390/metabo11010037 - 6 Jan 2021

Cited by 37 | Viewed by 5337

Abstract

Homocysteine (HCY), a physiological amino acid formed when proteins break down, leads to a pathological condition called hyperhomocysteinemia (HHCY), when it is over a definite limit. It is well known that an increase in HCY levels in blood, can contribute to arterial damage [...] Read more.

Homocysteine (HCY), a physiological amino acid formed when proteins break down, leads to a pathological condition called hyperhomocysteinemia (HHCY), when it is over a definite limit. It is well known that an increase in HCY levels in blood, can contribute to arterial damage and several cardiovascular disease, but the knowledge about the relationship between HCY and brain disorders is very poor. Recent studies demonstrated that an alteration in HCY metabolism or a deficiency in folate or vitamin B12 can cause altered methylation and/or redox potentials, that leads to a modification on calcium influx in cells, or into an accumulation in amyloid and/or tau protein involving a cascade of events that culminate in apoptosis, and, in the worst conditions, neuronal death. The present review will thus summarize how much is known about the possible role of HHCY in neurodegenerative disease. Full article

(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)

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12 pages, 2131 KiB

Open AccessArticle

Theoretical Analysis of the Built-in Metabolic Pathway Effect on the Metabolism of Erythrocyte-Bioreactors That Neutralize Ammonium

by Evgeniy Protasov, Larisa Koleva, Elizaveta Bovt, Fazoil I. Ataullakhanov and Elena Sinauridze

Metabolites 2021, 11(1), 36; https://doi.org/10.3390/metabo11010036 - 6 Jan 2021

Cited by 3 | Viewed by 2156

Abstract

The limitations of the efficiency of ammonium-neutralizing erythrocyte-bioreactors based on glutamate dehydrogenase and alanine aminotransferase reactions were analyzed using a mathematical model. At low pyruvate concentrations in the external medium (below about 0.3 mM), the main limiting factor is the rate of pyruvate [...] Read more.

The limitations of the efficiency of ammonium-neutralizing erythrocyte-bioreactors based on glutamate dehydrogenase and alanine aminotransferase reactions were analyzed using a mathematical model. At low pyruvate concentrations in the external medium (below about 0.3 mM), the main limiting factor is the rate of pyruvate influx into the erythrocyte from the outside, and at higher concentrations, it is the disappearance of a steady state in glycolysis if the rate of ammonium processing is higher than the critical value (about 12 mM/h). This rate corresponds to different values of glutamate dehydrogenase activity at different concentrations of pyruvate in plasma. Oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) by glutamate dehydrogenase decreases the fraction of NADPH in the constant pool of nicotinamide adenine dinucleotide phosphates (NADP + NADPH). This, in turn, activates the pentose phosphate pathway, where NADP reduces to NADPH. Due to the increase in flux through the pentose phosphate pathway, stabilization of the ATP concentration becomes impossible; its value increases until almost the entire pool of adenylates transforms into the ATP form. As the pool of adenylates is constant, the ADP concentration decreases dramatically. This slows the pyruvate kinase reaction, leading to the disappearance of the steady state in glycolysis. Full article

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3 pages, 177 KiB

Open AccessEditorial

Special Issue “Metabolic Engineering and Synthetic Biology Volume 2”

by An N. T. Phan and Lars M. Blank

Metabolites 2021, 11(1), 35; https://doi.org/10.3390/metabo11010035 - 6 Jan 2021

Viewed by 2005

Abstract

In times of ever-increasing demand for chemicals and the subsequent increase in CO₂ in the atmosphere, we have to intensify our efforts to establish a circular (bio) economy [...] Full article

(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology Volume 2)

11 pages, 1374 KiB

Open AccessEditor’s ChoiceArticle

Amino Acid and Acylcarnitine Levels in Chronic Patients with Schizophrenia: A Preliminary Study

by Irina A. Mednova, Alexander A. Chernonosov, Marat F. Kasakin, Elena G. Kornetova, Arkadiy V. Semke, Nikolay A. Bokhan, Vladimir V. Koval and Svetlana A. Ivanova

Metabolites 2021, 11(1), 34; https://doi.org/10.3390/metabo11010034 - 5 Jan 2021

Cited by 13 | Viewed by 2907

Abstract

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with [...] Read more.

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with ‘omics’ technology to study their contribution. The aim of our study was to investigate serum amino acid and acylcarnitine levels in antipsychotics-treated patients with chronic schizophrenia compared with healthy donors. We measured serum levels of 15 amino acids and 30 acylcarnitines in 37 patients with schizophrenia and 36 healthy donors by means of tandem mass spectrometry. In summary, patients with chronic schizophrenia had an altered concentration of a few amino acids and acylcarnitines in comparison to the healthy probands. Further research is needed to assess and understand the identified changes. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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9 pages, 1320 KiB

Open AccessArticle

Application of Carbon-13 Isotopomer Analysis to Assess Perinatal Myocardial Glucose Metabolism in Sheep

by Mukundan Ragavan, Mengchen Li, Anthony G. Giacalone, Charles E. Wood, Maureen Keller-Wood and Matthew E. Merritt

Metabolites 2021, 11(1), 33; https://doi.org/10.3390/metabo11010033 - 5 Jan 2021

Cited by 2 | Viewed by 3191

Abstract

Ovine models of pregnancy have been used extensively to study maternal–fetal interactions and have provided considerable insight into nutrient transfer to the fetus. Ovine models have also been utilized to study congenital heart diseases. In this work, we demonstrate a comprehensive assessment of [...] Read more.

Ovine models of pregnancy have been used extensively to study maternal–fetal interactions and have provided considerable insight into nutrient transfer to the fetus. Ovine models have also been utilized to study congenital heart diseases. In this work, we demonstrate a comprehensive assessment of heart function and metabolism using a perinatal model of heart function with the addition of a [U-¹³C]glucose as tracer to study central energy metabolism. Using nuclear magnetic resonance spectroscopy, and metabolic modelling, we estimate myocardial citric acid cycle turnover (normalized for oxygen consumption), substrate selection, and anaplerotic fluxes. This methodology can be applied to studying acute and chronic effects of hormonal signaling in future studies. Full article

(This article belongs to the Special Issue Stable Isotope Guided Metabolomics)

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20 pages, 996 KiB

Open AccessReview

Analytical Platforms for the Determination of Phospholipid Turnover in Breast Cancer Tissue: Role of Phospholipase Activity in Breast Cancer Development

by Rosa Perestrelo, Marijana Petkovic and Catarina Luís Silva

Metabolites 2021, 11(1), 32; https://doi.org/10.3390/metabo11010032 - 4 Jan 2021

Cited by 6 | Viewed by 2685

Abstract

Altered lipid metabolism has been associated with the progression of various cancers, and aberrant expression of enzymes involved in the lipid metabolism has been detected in different stages of cancer. Breast cancer (BC) is one of the cancer types known to be associated [...] Read more.

Altered lipid metabolism has been associated with the progression of various cancers, and aberrant expression of enzymes involved in the lipid metabolism has been detected in different stages of cancer. Breast cancer (BC) is one of the cancer types known to be associated with alterations in the lipid metabolism and overexpression of enzymes involved in this metabolism. It has been demonstrated that inhibition of the activity of certain enzymes, such as that of phospholipase A₂ in BC cell lines sensitizes these cells and decreases the IC₅₀ values for forthcoming therapy with traditional drugs, such as doxorubicin and tamoxifen. Moreover, other phospholipases, such as phospholipase C and D, are involved in intracellular signal transduction, which emphasizes their importance in cancer development. Finally, BC is assumed to be dependent on the diet and the composition of lipids in nutrients. Despite their importance, analytical approaches that can associate the activity of phospholipases with changes in the lipid composition and distribution in cancer tissues are not yet standardized. In this review, an overview of various analytical platforms that are applied on the study of lipids and phospholipase activity in BC tissues will be given, as well as their association with cancer diagnosis and tumor progression. The methods that are applied to tissues obtained from the BC patients will be emphasized and critically evaluated, regarding their applicability in oncology. Full article

(This article belongs to the Special Issue Metabolomic Approaches Combined with Statistical Methods as Cancer Diagnostic Tools)

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16 pages, 10218 KiB

Open AccessArticle

Quantitative Analysis of Biogenic Amines in Different Cheese Varieties Obtained from the Korean Domestic and Retail Markets

by Sujatha Kandasamy, Jayeon Yoo, Jeonghee Yun, Han Byul Kang, Kuk-Hwan Seol and Jun-Sang Ham

Metabolites 2021, 11(1), 31; https://doi.org/10.3390/metabo11010031 - 4 Jan 2021

Cited by 25 | Viewed by 3098

Abstract

To evaluate the safety and risk assessment of cheese consumption in the Republic of Korea, sixty cheese samples purchased from the farmstead and retails markets (imported) were analyzed for their biogenic amine (BA) contents. The BA profiles and quantities of eight amines (tryptamine, [...] Read more.

To evaluate the safety and risk assessment of cheese consumption in the Republic of Korea, sixty cheese samples purchased from the farmstead and retails markets (imported) were analyzed for their biogenic amine (BA) contents. The BA profiles and quantities of eight amines (tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine) were determined using high-performance liquid chromatography (HPLC). Spermine was the only amine detectable in all the samples. The BAs of fresh cheeses from both farmstead and retail markets were mostly undetectable, and comparatively at lower levels (<125 mg/kg) than ripened samples. Putrescine was undetectable in all the domestic ripened cheeses. The sum of BA levels in the imported ripened cheeses of Pecorino Romano (1889.75 mg/kg) and Grana Padano (1237.80 mg/kg) exceeds >1000 mg/kg, of which histamine accounts nearly 86 and 77% of the total levels, respectively. The tolerable limits of the potential toxic amines, histamine and tyramine surpassed in four and three imported ripened samples, respectively. Furthermore, the presence of potentiators (putrescine and cadaverine) together in samples even with a lower level of toxic amines alarms the risk in consumption. Therefore, adoption of strict hygienic practices during the entire chain of cheese production, along with obligatory monitoring and regulation of BA in cheeses seems to be mandatory to ensure the safety of the consumers. Full article

(This article belongs to the Special Issue Metabolomic Analysis in Food Science)

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