Folate-requiring reactions, collectively referred to as one-carbon metabolism, include those involved in phases of amino acid metabolism, purine and pyrimidine synthesis, and the formation of the primary methylating agent, S-adenosylmethionine (SAM).
The central folate acceptor molecule in the one-carbon cycle is a polyglutamyl form of tetrahydrofolate (THF) (Wagner 1995). The principal function of folate coenzymes is to accept or donate one-carbon units in key metabolic pathways. The conversion of THF to 5,10-methylene-THF is a crucial first step in the cycle that employs the 3-carbon of serine as a major carbon source. This one-carbon unit is transferred from serine to THF via pyridoxal phosphate (PLP)-dependent serine hydroxymethyltransferase (SHMT) to form 5,10-methylene-THF and glycine.
A portion of the 5,10-methylenetetrahydrofolate thus produced undergoes irreversible enzymatic reduction to the methyl oxidation state (as 5-methyl-THF) by methylene tetrahydrofolate reductase (MTHFR). The N-5 methyl group of 5-methyl-THF can only be used metabolically for transfer to homocysteine, which results in the (re)generation of methionine.
MTHFR serves a key role in one-carbon metabolism by converting methylene-THF to 5-methyl-THF, thus irreversibly directing this one-carbon moiety to methylation of homocysteine synthesis. Between 50 and 80% of the homocysteine generated is remethylated, depending on the dietary content of methionine and choline. In the methionine synthase reaction, a methyl group is removed from 5-methyl-THF, which functions as a substrate, and is sequentially transferred to the vitamin B-12 coenzyme before homocysteine, thus forming methionine.
In addition to protein synthesis, methionine serves as a methyl group donor through conversion to SAM, a key biological methylating agent involved in >100 methyltransferase reactions with a wide variety of acceptor molecules. (source)