Interplays and functional divergences of one-carbon metabolic shunts.

One-carbon (1C) metabolism serves as a central hub governing anabolism-supporting and epigenetic modification processes through its shunts, the tetrahydrofolate (THF) cycle, and the methionine cycle. The 1C shunts exhibit divergent characteristics in mammalian cells in terms of methyl sources, regulatory networks, and supporting functions. Under specific physiological and pathological contexts, 1C metabolic shunts exhibit distinct biological functions and orchestrate metabolic crosstalk between cells and across organs. These findings have significantly advanced our understanding of systemic compartmentalization and functional cooperation between the divergent 1C shunts. In this review, we explore the intricate interplays and divergent biological roles between the THF and methionine cycles at the molecular, cellular, and systemic levels and further propose innovative avenues for research and clinical applications.