Our cells work like factories and have particular processes of keeping their survival, proliferation and differentiation, known as cell metabolism. Changes in cell metabolism reflect interactions between genetic, epigenetic and environmental changes. Thus, in order to better understand the regulation of cell metabolism, one needs to analyse and quantify levels of proteins and metabolites. Since metabolite concentration is in constant flux, it is necessary to employ metabolic flux analysis or, at least, tracer-based metabolism (rather than static metabolite levels) to elucidate metabolic mechanisms in cells.
Using substances to trace the course of a chemical or biological process (tracer-based analyses), it is possible to determine the intermediates and products of metabolism in cells, and changes in metabolites can be assigned to particular mechanisms. So, the authors highlight that “tracer-based analyses offers considerable opportunities in the context of metabolism in various diseases including cancer.”
For this purpose, Nuclear Magnetic Resonance (NMR) spectroscopy is an attractive technique as it can quantify site-specific label incorporation. However, for applications using human cells and cell lines, the challenge is to optimize the process in order to maximize sensitivity and reproducibility.
Recently, researchers from the University of Birmingham, England, developed a new framework to analyse metabolism in hematological and liver cancer cell lines using NMR spectroscopy.
Figure 1 - Workflow for NMR tracer-based metabolism. Unlabelled and labelled precursors were used in cell cultures in order to study the flow of label from isotopically labelled precursors into other metabolistes.
Throughout the scientific article, the researchers explain in detail all the steps of the workflow (Figure 1), from the cell culture to metabolic analysis, as well as the materials used and the results obtained. To find out more about these details, consult the reference article.
They applied this new framework in hematological and liver cancer cell lines and confirm its feasibility, reporting that “tracer-based metabolism in primary liver samples has great potential for diagnostic purposes in translational medicine”.
Concluding, the researchers consider that“this approach is relevant for future drug discovery in the field of metabolism, and also for elucidating the mechanistic differences between healthy and diseased states in cell lines”.
Reference:
Saborano, R., Eraslan, Z., Roberts, J., Khanim, F.L., Lator, P.F., Reed, M.A.C., Günther, U,L. (2019). A framework for tracer-based metabolism in mammalian cells by NMR. Scientific Reports, 9:2520, 1-13. DOI: 10.1038/s41598-018-37525-3
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