Epimetabolites: discovering metabolism beyond building and burning

Showalter, Megan R.; Čajka, Tomáš; Fiehn, Oliver

doi:10.1016/j.cbpa.2017.01.012

Cited by 47 publications

(44 citation statements)

References 58 publications

(56 reference statements)

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“…Indeed, they are now so plentiful that it is probably no longer possible to feature them all in a comprehensive review. Several recent reviews provide very good coverage on a topic‐by‐topic basis, however (Fridman and Pichersky, ; Tholl et al ., ; Gaquerel et al ., ; Feussner and Polle, ; Sumner et al ., ; Dong et al ., ; Tenenboim and Brotman, ; Wen et al ., ; Rai et al ., ; Showalter et al ., ). In the current article we plan mainly to review classical papers and provide a perspective of the challenges that remain both with regards to technical aspects but also in defining the in vivo function of metabolites (for highlight see Box 1).…”

Section: Introductionmentioning

confidence: 97%

Metabolomics 20 years on: what have we learned and what hurdles remain?

2018

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The term metabolome was coined in 1998, by analogy to genome, transcriptome and proteome. The first research papers using the terms metabolomics, metabonomics, metabolic profiling or metabolite profiling were published shortly thereafter. In this short review we reflect on the major achievements brought about by the use of these approaches, and document the knowledge and technology gaps that are currently constraining its further development. Finally, we detail why we think that the time is ripe to refocus our efforts on the understanding of metabolic function.

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Section: Introductionmentioning

confidence: 97%

Metabolomics 20 years on: what have we learned and what hurdles remain?

2018

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“…Beyond proteins, the more intriguing point is that many metabolites themselves are targets of acetylation, prompting some to call these epi-metabolites (Showalter et al, 2017). For examples, some amino acids, neurotransmitters or polysaccharides such as glucosamine and muramic acid are all substrates of acetyl-CoA-dependent acetyltransferases (Engelke et al, 2004;Vetting et al, 2005;Han et al, 2012;Showalter et al, 2017;Christensen et al, 2019).…”

Section: Mechanisms Of Acetylation Of Metabolites and Histones Hint Amentioning

confidence: 99%

Who Rules the Cell? An Epi-Tale of Histone, DNA, RNA, and the Metabolic Deep State

Leung

Gaudin

2020

Front. Plant Sci.

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Epigenetics refers to the mode of inheritance independent of mutational changes in the DNA. Early evidence has revealed methylation, acetylation, and phosphorylation of histones, as well as methylation of DNA as part of the underlying mechanisms. The recent awareness that many human diseases have in fact an epigenetic basis, due to unbalanced diets, has led to a resurgence of interest in how epigenetics might be connected with, or even controlled by, metabolism. The Next-Generation genomic technologies have now unleashed torrents of results exposing a wondrous array of metabolites that are covalently attached to selective sites on histones, DNA and RNA. Metabolites are often cofactors or targets of chromatin-modifying enzymes. Many metabolites themselves can be acetylated or methylated. This indicates that the acetylome and methylome can actually be deep and pervasive networks to ensure the nuclear activities are coordinated with the metabolic status of the cell. The discovery of novel histone marks also raises the question on the types of pathways by which their corresponding metabolites are replenished, how they are corralled to the specific histone residues and how they are recognized. Further, atypical cytosines and uracil have also been found in eukaryotic genomes. Although these new and extensive connections between metabolism and epigenetics have been established mostly in animal models, parallels must exist in plants, inasmuch as many of the basic components of chromatin and its modifying enzymes are conserved. Plants are chemical factories constantly responding to stress. Plants, therefore, should lend themselves readily for identifying new endogenous metabolites that are also modulators of nuclear activities in adapting to stress.

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“…Among the ‐omics studies currently gaining traction is "epimetabolomics," a new area of study which specifically investigates metabolites that are modified classical metabolites; these metabolites play a role in the regulation of histone demethylation in epigenetic regulations, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, tumorigenesis, stem cell pluripotency status, inhibition of nitric oxide signaling, and other cellular processes . Resources such as the metabolic in silico expansion database (MINE DB) allow the obtainment of possible and new molecular structures that are predicted by enzyme promiscuity from canonical pathways and lead to the capture of metabolites that are novel or have a novel function.…”

Section: Coverage and Comparability With Other‐omics For A Systems Viewmentioning

confidence: 99%

Challenges and Opportunities in Cancer Metabolomics

Kumar

Misra

2019

Proteomics

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Challenges in metabolomics for a given spectrum of disease are more or less comparable, ranging from the accurate measurement of metabolite abundance, compound annotation, identification of unknown constituents, and interpretation of untargeted and analysis of high throughput targeted metabolomics data leading to the identification of biomarkers. However, metabolomics approaches in cancer studies specifically suffer from several additional challenges and require robust ways to sample the cells and tissues in order to tackle the constantly evolving cancer landscape. These constraints include, but are not limited to, discriminating the signals from given cell types and those that are cancer specific, discerning signals that are systemic and confounded, cell culture‐based challenges associated with cell line identities and media standardizations, the need to look beyond Warburg effects, citrate cycle, lactate metabolism, and identifying and developing technologies to precisely and effectively sample and profile the heterogeneous tumor environment. This review article discusses some of the current and pertinent hurdles in cancer metabolomics studies. In addition, it addresses some of the most recent and exciting developments in metabolomics that may address some of these issues. The aim of this article is to update the oncometabolomics research community about the challenges and potential solutions to these issues.

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Epimetabolites: discovering metabolism beyond building and burning

Cited by 47 publications

References 58 publications

Metabolomics 20 years on: what have we learned and what hurdles remain?

Metabolomics 20 years on: what have we learned and what hurdles remain?

Who Rules the Cell? An Epi-Tale of Histone, DNA, RNA, and the Metabolic Deep State

Challenges and Opportunities in Cancer Metabolomics

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