Enalomics: A Mass Spectrometry-Based Approach for Profiling, Identifying, and Semiquantifying Enals in Biological Samples

Human
cells generate a bulk of aldehydes during lipid peroxidation
(LPO), influencing critical cellular processes, such as oxidative
stress, protein modification, and DNA damage. Enals, highly reactive
α,β-unsaturated aldehydic metabolites, are implicated
in various human pathologies, especially neurodegenerative disorders,
cancer, and cardiovascular diseases. Despite their importance, endogenous
enals remain poorly characterized, primarily due to their instability
and low abundance. Herein, we introduced “enalomics,”
a mass spectrometry (MS)-based approach for profiling, identifying,
and semiquantifying enals in biological samples. Derivatization with
2,4-dinitrophenylhydrazine and treatment with ascorbic acid stabilized
enals in biological matrices and provided a unique MS fragment ([M-H-47]−) for reliable enal identification. Utilizing precursor
ion scanning, dynamic multiple reaction monitoring, high-resolution
MS, and mathematical correlations between retention times and carbon
numbers of enals, we identified 157 enals (127 newly reported) with
tissue-specific profiles in rats and 29 enals (24 newly reported)
in human plasma. To the best of our knowledge, this represents the
comprehensive analysis of enals, i.e., “enalomics,”
in biological samples. Enalomics demonstrated significant alterations
in enal metabolism in rats with myocardial injury, highlighting the
potential of medium- and short-chain plasma enals as sensitive diagnostic
biomarkers. Further application of enalomics in patients with myocardial
infarction (MI) identified 14 plasma diagnostic biomarkers. Receiver
operating characteristic curves showed good discrimination (area under
curve ≥ 0.8603, p ≤ 0.0043).
This research advances the understanding of LPO products and emphasizes
the roles of enals in human diseases, offering good prospects for
early screening, diagnosis, and clinical interventions targeting LPO
products in MI patients.