Metabolites beyond metabolism: Exploring their atypical roles in protein modification and signaling transduction

This comprehensive review explores the atypical metabolic roles of metabolites, extending beyond their conventional functions in energy production and biosynthesis. It systematically discusses how metabolites serve as substrates for post-translational protein modifications (PTMs), including lactylation, acetylation, and palmitoylation, detailing their metabolic origins, enzymatic regulation, and impacts on development, homeostasis, and diseases. Additionally, the review highlights how metabolites and metabolic enzymes act as signaling molecules to modulate intracellular and intercellular signal transduction, influencing processes like cell differentiation, survival, and proliferation. Unlike previous reviews, this work integrates PTM mechanisms with metabolic signaling networks, aiming to inspire research on metabolic regulation in health and disease, and to identify novel therapeutic targets.