Figure 1.

One carbon metabolism is a collection of cyclical metabolic pathways that orchestrates myriad metabolic processes. The one carbon pathway is comprised of the folate cycle and the methionine cycle. Folate enters the pathway through a two-step reaction that generates tetrahydrofolate (THF) with the dihydrofolate reductase enzyme (DHFR). Within the methionine cycle, dietary methionine is catabolized by methionine adenosyltransferase 2A or 1A (MAT2A/MAT1A) to produce the universal methyl donor S-adenosylmethionine (SAM). Upon substrate methylation, SAM is converted to S-adenosylhomocysteine (SAH) and then converted by adenosylhomocysteinase (AHCY) to homocysteine (Hcy). The methionine cycle is completed by the conversion of Hcy back to methionine by methionine synthase (MS). Alternatively, Hcy can fed into the transsulfuration pathway for glutathione synthesis and redox metabolism using vitamin B6-dependent enzymes. The methionine salvage pathway also sparks off the methionine cycle to produce the by-product methylthioadenosine (MTA) from methionine for polyamine biosynthesis. Figure made with BioRender.