描述
Folates are essential cofactors that provide one-carbon moieties in various states of reduction for biosynthetic reactions. The processes shown in this pathway include transport reactions by which folates are taken up by cells and moved intracellularly, folate conjugation with glutamate (required for folate retention within a cell), as well as the synthesis of pterines, which are used in folate synthesis. Two branches are depicted: Pterin synthesis and Folate biosynthesis. In pterin synthesis, GTP is the precursor for pterin biosynthesis. The enzyme GTP-cyclohydrolase I produces dihydroneopterin triphosphate from GTP as the first step. The product is then dephosphorylated to dihydroneopterin and yields, after removal of a C2-residue from the C3-side chain 6- hydroxymethyldihydropterin, which is the precursor for folate biosynthesis. In terms of folate biosynthesis, the basic steps are: folate → dihydrofolate → tetrahydrofolate ? methylene-THF → methyl-THF. More specifically, the pathway leading to the formation of tetrahydrofolate (FH4) begins when folate (F) is reduced to dihydrofolate (DHF) (FH2), which is then reduced to THF. Dihydrofolate reductase catalyses the last step. Vitamin B3 in the form of NADPH is a necessary cofactor for both steps of the synthesis. Methylene-THF (CH2FH4) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH3-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. Another form of THF, formyl-THF (or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Finally, histidine can donate a single carbon to THF to form methenyl-THF.