Metabolomics: Definitions and Significance in Systems Biology

Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; Cruz, Pedro Luis Rocha da; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

doi:10.1007/978-3-319-47656-8_1

Cited by 84 publications

(71 citation statements)

References 91 publications

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“…Found in widespread genera such as Microcystis, Dolichospermum (Anabaena), between and within organisms in response to environmental stressors. Untargeted metabolomics (also referred to as nontarget analysis) studies the overall change of the metabolome without targeting specific compounds; it is a qualitative analysis that facilitates the detection of metabolites without prior knowledge of their presence, as well as potentially novel compounds [30]. Cyanobacteria metabolites have been studied by applying both targeted and untargeted metabolomics approaches with a major focus on microcystins [31][32][33][34][35][36][37][38][39][40] while targeted metabolomics have most commonly been applied to enable the identification of a few less studied metabolites (e.g., aeruginosins, β-methylamino-L-alanine, cyanobactins) [41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Metabolome Variation between Strains of Microcystis aeruginosa by Untargeted Mass Spectrometry

Racine

Saleem

Pick

2019

Toxins

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Cyanobacteria are notorious for their potential to produce hepatotoxic microcystins (MCs), but other bioactive compounds synthesized in the cells could be as toxic, and thus present interest for characterization. Ultra performance liquid chromatography and high-resolution accurate mass spectrometry (UPLC-QTOF-MS/MS) combined with untargeted analysis was used to compare the metabolomes of five different strains of the common bloom-forming cyanobacterium, Microcystis aeruginosa. Even in microcystin-producing strains, other classes of oligopeptides including cyanopeptolins, aeruginosins, and aerucyclamides, were often the more dominant compounds. The distinct and large variation between strains of the same widespread species highlights the need to characterize the metabolome of a larger number of cyanobacteria, especially as several metabolites other than microcystins can affect ecological and human health.Key Contribution: Metabolome variation between M. aeruginosa strains, highlighted by oligopeptide detection and identification, using a new, untargeted analytical workflow.Toxins 2019, 11, 723 2 of 18 and Planktothrix [17,18], MCs cause the inhibition of protein phosphatases 2A and 1 in vertebrates, which leads to an accumulation of phosphorylated proteins in cells. This accumulation can affect different metabolic pathways, including the inhibition of tumor suppressor proteins, cell proliferation and eventually, death [9,[19][20][21]. Despite many ecological impacts, the biological role of MCs within cyanobacteria remains unknown, which makes their control difficult. Remarkably, the cell concentrations of MCs in toxigenic taxa can reach those of chlorophyll a [22], the primary pigment involved in photosynthesis in cyanobacteria, algae and higher plants.Thus far over 269 variants have been identified with molecular weights varying between 880 and 1200 Da [10,23]. Amino acid variation in various positions of the cyclic molecule affects the degree of toxicity in vertebrates, as shown by LD 50 values between 50 µg/kg (MC-LA) and 800 µg/kg (MC-RR) in mice after intraperitoneal injection [16]. Microcystins are thus potentially more lethal to vertebrates than several highly potent poisons, such as sarin [24]. Increasing toxic effects are observed when hydrophobic amino acids (e.g., methylated amino acids) are present in the molecule, which can facilitate MC penetration into the tissues [25]. However, the ADDA moiety of the molecule (3-amino-9-methoxy-10-phenyl-2,6,8-trimethyldeca-4,6-dienoic acid), found in all MC variants, is known to have a major role in the toxicity [25].In addition to microcystins, cyanobacteria can produce a wide range of bioactive compounds. These include an extraordinary diversity of oligopeptides (e.g., cyanopeptolins, aeruginosins, microviridins) [26]. Several may also be bioactive or even toxic to vertebrates since many are produced through the same metabolic pathway as the MCs [27] and have similar structures [28]. Besides the public and environmental health needs for more research on these co...

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Section: Introductionmentioning

confidence: 99%

Metabolome Variation between Strains of Microcystis aeruginosa by Untargeted Mass Spectrometry

Racine

Saleem

Pick

2019

Toxins

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“…It so could be of interest to validate our data by a MS-based technique, considered more sensitive, more specific and providing more accurate quantification. The advantage of combining the two techniques has been reviewed recently [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Does the 1H-NMR plasma metabolome reflect the host-tumor interactions in human breast cancer?

et al. 2017

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Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters. In particular lactate levels are inversely correlated with the tumor size in the EBC cohort (Pearson correlation r = −0.309; p = 0.044). We suggest that, in BC patients, tumor cells could induce modulation of the whole patient's metabolism even at early stages. If confirmed in a lager study these observations could be of clinical importance.

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“…The higher sensitivity of metabolite detection in MS experiments (lower than 10μmol L −1 ) faces some problems involving the compatibility of molecules with a mode of ionization or detection, and might require previous steps of analysis, as separation by high- or ultra-performance liquid chromatography (HPLC or UPLC), with the aim to reduce sample complexity and enhance detection sensibility and metabolome coverage [ 21 , 22 , 23 ]. Additionally, those separation techniques also have their particularities, such as the need for the derivatization process that converts metabolites into volatile adducts in GC based experiments.…”

Section: Introductionmentioning

confidence: 99%

Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

et al. 2020

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There are, still, limitations to predicting the occurrence and prognosis of neurological disorders. Biomarkers are molecules that can change in different conditions, a feature that makes them potential tools to improve the diagnosis of disease, establish a prognosis, and monitor treatments. Metabolites can be used as biomarkers, and are small molecules derived from the metabolic process found in different biological media, such as tissue samples, cells, or biofluids. They can be identified using various strategies, targeted or untargeted experiments, and by different techniques, such as high-performance liquid chromatography, mass spectrometry, or nuclear magnetic resonance. In this review, we aim to discuss the current knowledge about metabolites as biomarkers for neurological disorders. We will present recent developments that show the need and the feasibility of identifying such biomarkers in different neurological disorders, as well as discuss relevant research findings in the field of metabolomics that are helping to unravel the mechanisms underlying neurological disorders. Although several relevant results have been reported in metabolomic studies in patients with neurological diseases, there is still a long way to go for the clinical use of metabolites as potential biomarkers in these disorders, and more research in the field is needed.

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Metabolomics: Definitions and Significance in Systems Biology

Cited by 84 publications

References 91 publications

Metabolome Variation between Strains of Microcystis aeruginosa by Untargeted Mass Spectrometry

Metabolome Variation between Strains of Microcystis aeruginosa by Untargeted Mass Spectrometry

Does the 1H-NMR plasma metabolome reflect the host-tumor interactions in human breast cancer?

Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

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