Folic Acid Metabolism | Folate Cycle

Folate, also known as vitamin B9 and folacin,is one of the B vitamins.
Folate (vitamin B9) refers to the many forms of folic acid and its related compounds, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid, folacin, and pteroylglutamic acid. Historic names included L. ⁠casei factor, vitamin Bc and vitamin M.[2]

The terms folate and folic acid have somewhat different meanings in different contexts, although sometimes used interchangeably. Within the field of organic chemistry, folate refers to the conjugate base of folic acid. Within the field of biochemistry, folates refer to a class of biologically active compounds related to and including folic acid.
All of the biological functions of folic acid are performed by THF and its methylated derivatives. Hence folic acid must first be reduced to THF. This four electron reduction proceeds in two chemical steps both catalyzed by the same enzyme, dihydrofolate reductase.Folic acid is first reduced to dihydrofolate and then to tetrahydrofolate. Each step consumes one molecule of NADPH (biosynthetically derived from vitamin B3) and produces one molecule of NADP.Mechanistically, hydride is transferred from NADPH to the C6 position of the pteridine ring.

A one-carbon (1C) methyl group is added to tetrahydrofolate through the action of serine hydroxymethyltransferase (SHMT) to yield 5,10-methylenetetrahydrofolate (5,10-CH2-THF). This reaction also consumes serine and pyridoxal phosphate (PLP; vitamin B6) and produces glycine and pyridoxal.[77] A second enzyme, methylenetetrahydrofolate dehydrogenase (MTHFD2)[80] oxidizes 5,10-methylenetetrahydrofolate to an iminium cation which in turn is hydrolyzed to produce 5-formyl-THF and 10-formyl-THF.[77] This series of reactions using the β-carbon atom of serine as the carbon source provide the largest part of the one-carbon units available to the cell.