Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Abstract

Vitamin B9, folate in its natural form is present in vegetables, fruits and organ meats. The function of folate is to act in processes of transfer one carbon compounds, methylation on nucleotides, amino acids and phospholipids, processes of vital importance for cell division, synthesis of nucleic acids, amino acids and methionine from homocysteine1. Folic acid is the synthetic form most used as a supplement to compensate low intakes of folate but has not normal biological actions if it is not converted to 5-methylenetetrahydrofolate, by the enzyme methylenetetrahydrofolate reductase. This enzyme may presents polymorphism due to mutation with biotypes of varied activity. The most commonly present, C677C and A1298A, has full activity, but C677T and T677T and A1298C and C1298C with decreased activity between 30 and 70 %, can cause metabolic alterations such as hyperhomocysteinemia and DNA hypomethylation with increased risk for chromosomal abnormalities and various pathological conditions, as neural tube development disorders, early recurrent pregnancy losses, Down syndrome, cleft lip and/or palate, limb reduction, cancer, mediterranean familial fever, polycystic ovarian syndrome and neurological or cardiovascular diseases. Faced with a history of these disorders and the presence of the aforementioned enzyme biotypes, the replacement of folic acid by L 5-methylenetetrahydrofolate supplied together with vitamin B12, B2, and B6 may reduce the risk. Beside this, with excessive intakes of folic acid, especially when low activity of the enzyme is preset, high levels in the blood can be produced, with consequently higher risk of various health problems. To avoid this, recommended intakes of folic acid should not be exceeded.