Figure 1.

General view of the one-carbon metabolism. Choline, an essential micronutrient, can be obtained from exogenous sources—for instance, from foods such as eggs, beans, fish, nuts, seeds, and whole grain-, and from endogenous biosynthesis. The de novo synthesis of choline is catalyzed by the enzymatic activity of phosphatidylethanolamine-methyltransferase (PEMT) via the sequential methylation of PE, using S-adenosylmethionine (SAM) as a methyl donor. The oxidation of choline into its metabolite betaine by choline oxidase plays a role in the formation of methionine and SAM, methyl-donors that are involved in methylation pathways. SAM is considered the main methyl-donor for histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), key enzymes that catalyze both histone and DNA methylation. Choline can also be acetylated into acetylcholine (Ach) by the enzymatic activity of choline acetyltransferase (ChAT). Methionine is central in a complex metabolic pathway that can be divided into three parts—methionine cycle, the transsulfuration pathway, and polyamine biosynthesis. Thus, methionine is converted to the universal methyl donor SAM, which upon donation of one methyl group is converted to S-adenosylhomocysteine (SAH). SAH is hydrolyzed into homocysteine, which can be used to regenerate methionine via the betaine or folate cycle. In addition, homocysteine can be remethylated to methionine via folate cycle, or can also enter into the transsulfuration pathway, and be sequentially converted into cystathionine and cysteine, in a series of reactions catalyzed by enzymes that use vitamin B6 as cofactor. Finally, this cysteine can be directed to the glutathione synthesis onto the synthesis of taurine.