Enzyme Research Reveals How Folic Acid Prevents Heart Disease, Birth Defects

Release Date:
Alison Davis, NIGMS

Scientists have known for decades that folic acid, one of the B vitamins, can protect against certain birth defects--such as spina bifida--that develop in the first few weeks after conception. For this reason, the Food and Drug Administration (FDA) recommends that every woman of child-bearing age supplement her diet with 400 extra micrograms of this vitamin. Folic acid supplements may also decrease the incidence of heart attacks and strokes in both men and women. More recent findings have suggested the way in which folic acid does its molecular good deeds, by lowering levels of a potentially harmful compound called homocysteine, a risk factor for heart attacks and strokes.

Drs. Rowena Matthews and Martha Ludwig, both of the University of Michigan, have succeeded in showing that folic acid performs this task by speeding up the conversion of homocysteine to an amino acid, called methionine, that the body needs to fuel myriad chemical reactions. Folic acid saves the day, the researchers show, by improving the fit between an enzyme and a helper molecule called a cofactor. The enzyme in this case is methylenetetrahydrofolate reductase (MTHFR), and the cofactor, a molecule called FAD, is also vitamin-derived (from vitamin B2) and is essential for converting homocysteine to methionine. The two scientists, who for years have been studying how the MTHFR enzyme works, determined that folic acid performs its protective role in the body by locking FAD onto MTHFR.

Besides bolstering the FDA guidelines on the importance of dietary folic acid for pregnant women, the new results provide solid evidence for the molecule's important and more general role in reducing homocysteine levels that are dangerously high in a variety of unhealthy states, such as heart disease. The work also points to possible therapies for these diseases, by upping folic acid intake in the diet, either through foods rich in the vitamin or vitamin pills.


Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nature Structural Biology 1999;6:359-65.

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