One Carbon Metabolism - The Missing Link for Cancer and Sepsis

One-carbon (1C) metabolism (OCM) is a biosynthetic and physiological process essential to cells. OCM encompasses a multitude of tightly regulated biochemical reactions that are responsible for nucleotide synthesis (purines and pyrimidines), amino acid homeostasis (Met, Ser, Gly), redox balance, and epigenetic regulation. Dysregulations of this pathway have been implicated in the development and progression of cancer and sepsis - two complex pathologies, each with a characteristically high morbidity and mortality rate. OCM changes in the oncogenic state have been extensively investigated, while metabolic pathway changes in sepsis remain more elusive. Given that emerging evidence suggests that 1 in 5 sepsis hospitalizations occur in patients with a cancer diagnosis, and recovering sepsis patients have a higher incidence of cancer diagnosis, our review aims to analyze the known OCM changes that occur in each pathology, highlight commonalities and variations, and suggest clinical implications that explore possible therapeutic targets. Through a novel cross-disease examination, a more comprehensive understanding of OCM metabolic changes in these disease states could inform clinical practice and lead to the development of targeted therapeutic interventions that further our understanding and treatment of one or both conditions.