MTHFR Is Not Your Problem: The Complete Methylation Architecture Science Has Never Fully Told You — section

Dietary folate enters the cell and is converted to dihydrofolate (DHF) by the enzyme DHFR &#8212; dihydrofolate reductase. DHFR then converts DHF to tetrahydrofolate (THF), the base form of active folate. THF is then acted on by SHMT1 &#8212; serine hydroxymethyltransferase, the cytoplasmic isoform &#8212; which uses serine to add a one-carbon unit, producing 5,10-methylene-THF. This is the direct substrate for MTHFR. MTHFR &#8212; methylenetetrahydrofolate reductase, the enzyme everyone has heard of &#8212; converts 5,10-methylene-THF to 5-methyl-THF. This reaction requires FAD, derived from riboflavin (vitamin B2), as a prosthetic cofactor. The output, 5-methyl-THF, is then handed to methionine synthase (MTR), which requires vitamin B12 as a cofactor to transfer the methyl group onto homocysteine, producing methionine. Methionine is then converted to S-adenosylmethionine &#8212; SAM &#8212; by the methionine adenosyltransferase enzymes MAT1A and MAT2A.