Metabolomics-Edited Transcriptomics Analysis (Meta)

The study of the metabolome or systems biochemical functions in response to external agents such as drugs or toxicants is made possible by recent advances in nuclear magnetic resonance (NMR) and mass spectrometry (MS). To optimize a given metabolomic study, samples should be processed with maintenance of biochemical integrity and optimal or reproducible recovery of metabolites. Various approaches to accomplish these goals were given. For metabolite profiling, both NMR and MS are excellently suited for providing molecular structure and abundance information. They are also uniquely suited for deciphering stable isotopomers of various metabolites in crude extracts. By coupling such analytical technologies with the stable isotope tracer approach, it is now practical to map changes in metabolic networks with atomic resolution such that metabolic perturbations can be discerned at individual enzyme reaction levels. This information readily lends its use in guiding transcriptomic analysis for metabolic regulations at the transcriptional level - an approach we called 'metabolomics-edited transcriptomic analysis' or META. An example study is given to illustrate the use of uniformly ¹³C-labeled glucose ([U-¹³C]-Glc) tracer, ¹³C-isotopomer-based metabolomic analysis, and META for reconstructing metabolic pathways and for discerning their regulatory pathways. This involved the investigation on defining the multitargeted action of selenite in human lung adenocarcinoma A549 cells. The META approach revealed 5? adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mediated downregulation of fatty acid and protein synthesis, in addition to negative regulation of glycolysis, pentose phosphate pathway (PPP), Krebs cycle, glutathione synthesis, and nucleotide synthesis, as well as positive regulation of Gln oxidation. The complexity of the selenite action including the induction of opposing regulatory events was resolvable with the integrated metabolomics and transcriptomics approach, which is also generally applicable to any living system including the human body.