Metabolomics as a Tool for Unraveling the Impact of Enantioselectivity in Cellular Metabolism

Metabolomics is an emerging interdisciplinary field focused on the comprehensive analysis of all metabolites within biological samples, making it valuable for areas such as drug development, and environmental analysis. Many compounds, including pharmaceuticals and agrochemicals that have been extensively studied by metabolomics are chiral. The intrinsic chirality of biological targets can lead to a selective recognition of enantiomers resulting in distinct pharmacokinetic, pharmacodynamic and/or toxicological profiles (enantioselectivity). Given that metabolomics captures an instant snapshot of an organism's metabolic state, it serves as a powerful tool to investigate chiral compounds and understand enantioselective effects. Herein, a systematic compilation of scientific literature was performed and 48 enantioselectivity studies using metabolomics were selected. These studies revealed an increasing focus on chiral pesticides (77%), the use of animal models (59%), reliance on LC-MS techniques (52%), and predominantly untargeted approaches (83%). Enantioselective effects were described in most studies. This review describes significant advances in this emerging field and highlights the use of metabolomics to unravel the role of stereochemistry in cellular metabolism by the examination of enantiomer-specific metabolic effects. Furthermore, it elucidates enantioselectivity mechanism that can be further applied to other groups of chiral compounds.