Epimetabolites: discovering metabolism beyond building and burning.

Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism. Epimetabolites are discovered by untargeted metabolomics using liquid- or gas chromatography-high resolution mass spectrometry and structurally annotated by in-silico fragmentation prediction tools. Their specific biological functions are subsequently investigated by targeted metabolomics methods.