Folic acid: nutritional biochemistry, molecular biology, and role in disease processes

This paper reviews the chemistry, metabolism, and molecular biology of folic acid, with a particular emphasis on how it is, or may be, involved in many disease processes. Folic acid prevents neural tube defects like spina bifida, while its ability to lower homocysteine suggests it might have a positive influence on cardiovascular disease. A role for this B vitamin in maintaining good health may, in fact, extend beyond these clinical conditions to encompass other birth defects, several types of cancer, dementia, affective disorders, Down's syndrome, and serious conditions affecting pregnancy outcome. The effect of folate in these conditions can be explained largely within the context of folate-dependent pathways leading to methionine and nucleotide biosynthesis, and genetic variability resulting from a number of common polymorphisms of folate-dependent enzymes involved in the homocysteine remethylation cycle. Allelic variants of folate genes that have a high frequency in the population, and that may play a role in disease formation include 677C --> T-MTHFR, 1298A --> C-MTHFR, 2756A --> G-MetSyn, and 66A --> G-MSR. Future work will probably uncover further polymorphisms of folate metabolism, and lead to a wider understanding of the interaction between this essential nutrient and the many genes which underpin its enzymatic utilization in a plethora of critical biosynthetic reactions, and which, under adverse nutritional conditions, may promote disease.