Structure-Function Relationships of Unusual Fatty Acids with Distinctive Functional Group Modifications and Carbon Chain Skeletons: Focus on the Roles of Double Bonds and Methyl Branches in Metabolism and Signaling.

Structurally unusual fatty acids (FAs) are biomolecules that connect lipid metabolism, membrane adaptation, and cellular communication. Evidence indicates that FA structural features, including double-bond position, stereochemical configuration, and methyl branches, influence physicochemical properties, metabolic fate, and biological functions. However, these mechanisms have not been systematically integrated. This review summarizes the structural characteristics and biological functions of epoxy, hydroxy, cyclopropane, acetylenic, and conjugated fatty acids. Among these, we focus particularly on structure-function relationships, metabolism of FAs with double bonds in uncommon positions and methyl branches, as these characteristics affect their recognition by metabolic enzymes and metabolic stability. We discuss the metabolic features and biological roles of structurally unusual FAs, with particular emphasis on how structural features regulate unsaturated FA β-oxidation. We clarify how double bonds affect isomerases and reductases through spatial configuration and how methyl branches may alter enzymatic recognition and slow degradation through steric effects. In diffusible signal factor (DSF)-family quorum-sensing signals, double bonds and methyl branches may contribute to the stability and effective concentration of signaling molecules by influencing β-oxidation-related turnover, potentially affecting signal intensity and duration. Overall, this review highlights the role of FA structures in linking metabolism with signal transduction. Future studies integrating biochemical assays, genetic analyses, and multi-omics approaches are needed to elucidate these mechanisms and expand applications.