Stability of energy metabolitesAn often overlooked issue in metabolomics studies: A review

Recent advances in analytical chemistry have set the stage for metabolite profiling to help understand complex molecular processes in physiology. Despite ongoing efforts, there are concerns regarding metabolomics workflows, since it has been shown that internal (enzyme activity, blood contamination, and the dynamic nature of metabolite concentrations) as well as external factors (storage, handling, and analysis method) may affect the metabolome profile. Many metabolites are intrinsically instable, particularly some of those associated with central carbon metabolism. While enzymatic conversions have been studied in great detail, nonenzymatic, chemical conversions received comparatively little attention. This review aims to give an in-depth overview of nonenzymatic energy metabolite degradation/interconversion chemistry focusing on a selected range of metabolites. Special attention will be given to qualitative (degradation pathways) as well as quantitative aspects, that may affect the acquisition of accurate data in the context of metabolomics studies. Problems related to the use of isotopically labeled internal standards hindering the quantitative analysis of common metabolites will be presented with an experimental example. Finally, general conclusions and perspectives are given.