Identification of bioactive metabolites using activity metabolomics

Abstract

The metabolome, the small molecule chemical entities involved in metabolism, has traditionally been studied with the aim of identifying biomarkers in the diagnosis and prediction of disease. However, the value of metabolomics has been redefined from a simple biomarker identification tool to a technology for the discovery of active drivers of biological processes. In this review, we describe the molecular mechanisms by which the active cell metabolome affects cellular physiology through modulation of other ‘omic’ levels, including the genome, epi-genome, transcriptome and proteome. This concept of activity screening guided by metabolomics to identify biologically active metabolites, or “activity metabolomics”, is having broad impact on biology.

The Aging Metabolome—Biomarkers to Hub Metabolites

“…Figure 1 briefly summarizes metabolomics workflows for analysis of biofluids and tissues using mass spectrometric approaches. These workflows have already been reviewed elsewhere [13][14][15][16][17][18] and are beyond the scope of the current review.…”

Challenges and Opportunities in Cancer Metabolomics

“…Similarly, efforts to capture RNA‐metabolite interactions have been explored using high throughput structure‐activity relationships through sequencing (HiT‐StARTS); these efforts uncovered a rich landscape of hundreds of thousands of RNA motif‐small molecule binding partners . For a more extensive and recent update on the role of metabolites regulating a diverse cellular functions, named as "activity metabolomics," readers are advised to consult Rinschen et al …”

“…Similarly, efforts to capture RNA-metabolite interactions have been explored using high throughput structure-activity relationships through sequencing (HiT-StARTS); these efforts uncovered a rich landscape of hundreds of thousands of RNA motif-small molecule binding partners. [72] For a more extensive and recent update on the role of metabolites regulating a diverse cellular functions, named as "activity metabolomics," readers are advised to consult Rinschen et al [73] 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. [74] Resources such as the metabolic in silico expansion database (MINE DB) [75] 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.…”

Dynamic metabolomic analysis of intestinal ischemia–reperfusion injury in rats

“…Metabolomics, using the techniques of mass spectrometry and nuclear magnetic resonance spectroscopy to identify and quantify small molecules (metabolites) in cells, biological fluids, tissues, or organisms, can directly reflect the underlying biochemical activity in time and bridge the difference between the genotype and phenotype, which is increasingly applied to improve individualized health.…”

“…Restoration of blood flow to the ischemic intestine tissue is critical to its salvage, yet, it may paradoxically magnify the damage to not only the intestine but also the distant organs by a cascade of events, such as inflammatory cytokines, 6 complement activation and oxygen-free radical formation. 7 Metabolomics, 8,9 using the techniques of mass spectrometry and nuclear magnetic resonance spectroscopy to identify and quantify small molecules (metabolites) in cells, biological fluids, tissues, or organisms, can directly reflect the underlying biochemical activity in time and bridge the difference between the genotype and phenotype, which is increasingly applied to improve individualized health.…”