folate-homocysteine metabolic pathway
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Folates are carriers of one-carbon units and are metabolized by 5,10-methylenetetrahydrofolate reductase (MTHFR) and other enzymes that use riboflavin, cobalamin, or vitamin B6 as cofactors.
These B vitamins are essential for the remethylation and transsulfuration of homocysteine, which is an important intermediate in one-carbon metabolism.
Folic acid is an inactive water-soluble B vitamin that is absorbed in the proximal small intestine via a carrier-mediated mechanism involving reduced folate carrier (RFC).
Once entered into the bloodstream, folate is transported into cells mainly through the folate receptor (FR-?, -? and -?) and through the RFC.
Once entered into the cell, folate acts as a methyl donor for methionine synthesis via homocysteine (Hcy) remethylation. Methionine is the single most important methyl donor for the methylation of DNA and tRNA.
Folate also acts a donor of one-carbon groups for synthesis of thymidine and purines, the building blocks of DNA.
Folate and Hcy metabolic cycles are closely related and involve over 25 proteins, many of which have been investigated for association with an increased NTD risk.
Key enzymes involved in folate and Hcy metabolism are 5,10-methylene-tetrahydrofolate reductase (MTHFR), the trifunctional enzyme methyleneTHF dehydrogenase/formylTHF synthase/methenylTHF cyclohydrolase (MTHFD), methionine synthase (MTR) and methionine synthase reductase (MTRR).
Pathology
susceptibility to spina bifida