Omics-scale capture of electrophilic metabolites
The majority of metabolic pathways rely on the production of activated electrophilic intermediates, e.g., coenzyme-A esters, and their chemical structures and abundances are central to understanding enzyme function and biochemical mechanisms. However, most electrophilic metabolites are lost in traditional metabolomic analysis and thus remain poorly characterized. Here we introduce a biochemical…
Metabolic pathways heavily depend on the formation of activated electrophilic intermediates, such as coenzyme-A esters, which play a crucial role in enzyme functionality and biochemical mechanisms. However, traditional metabolomic analysis often misses these electrophilic metabolites, leading to their poor characterization. Researchers have now developed a biochemical probe called O-(trimethylammoniobutyl)-hydroxylamine (TAMOHA) that allows for the comprehensive profiling of electrophilic species, including coenzyme-A esters, ketones, and aldehydes.
TAMOHA incorporates a highly nucleophilic hydroxyl amine that quickly reacts with electrophilic species upon tissue lysis, trapping them as stable derivatives. These derivatives possess a tetraalkylammonium moiety with a distinct charge and a characteristic MS2 fragmentation fingerprint, enabling their sensitive detection. By employing TAMOHA to analyze the electrophilomes of E. coli, C. elegans, and mouse, the researchers identified several thousand previously uncharacterized electrophilic metabolites.
The study further demonstrates the effectiveness of TAMOHA in trapping electrophilic metabolites within specific biochemical pathways. The researchers confirm the previously proposed functions of two fatty acid metabolism enzymes, detect formaldehyde production in mice, and gain new insights into the biosynthesis of ascaroside pheromones in C. elegans.
The authors believe that utilizing TAMOHA for profiling electrophilic species will provide valuable information on enzyme function and uncover previously unknown biochemical mechanisms across various biological systems.
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