Lack of key enzyme in the metabolism of folic acid leads to birth defects

January 17, 2013

Researchers at The University of Texas at Austin have discovered that the lack of a critical enzyme in the folic acid metabolic pathway leads to neural tube birth defects in developing embryos.

It has been known for several decades that folic acid supplementation dramatically reduces the incidence of neural tube defects, such as and , which are among the most common birth defects. In some populations, folic acid supplementation has decreased neural tube defects by as much as 70 percent.

However, scientists still do not fully understand how folic acid decreases neural tube defects, or why folic acid supplementation does not eliminate birth defects in all pregnancies.

"Now, we've found that mutation of a key folic acid enzyme causes neural tube defects in mice," said Dean Appling, professor of biochemistry in the College of Natural Sciences. "This is the clearest mechanistic link yet between folic acid and birth defects."

Appling and his colleagues published their research in the Jan. 8 issue of (PNAS).

The scientists made the discovery using mice that lack a gene for a folic acid enzyme called Mthfd1l, which is required for cells to produce a metabolite called formate. Embryos need formate to develop normally.

"This work reveals that one of the ways that folic acid prevents birth defects is by ensuring the production of formate in the developing embryo," said Appling, "and it may explain those 30 percent of neural tube defects that cannot be prevented by folic acid supplementation."

Appling said that the mice provide researchers with a strong that they can use to further understand folic acid and its role in birth defects in humans. In fact, humans share the same gene for the folic acid enzyme with the mouse and all other mammals. Indeed, it has recently been discovered that point mutations in that increase the risk of birth defects.

Appling said that he and his colleagues would like to use the mouse system to begin looking for nutrients that could be delivered to pregnant mothers to prevent those neural tube defects that cannot be prevented by folic acid.

Ultimately, women could someday be screened for the gene that produces the enzyme. If they are deficient, steps could be taken to improve their chances for developing embryos free of through further nutrient supplementation.

Folic acid was discovered at The University of Texas at Austin in the 1940s by biochemists Esmond Snell and Herschel Mitchell. The U.S. has fortified all enriched cereal grain products with folic acid since 1996 to ensure that women of childbearing age receive adequate quantities of the vitamin.

Explore further: Fortifying corn masa flour with folic acid could prevent birth defects, March of Dimes says

Related Stories

Fortifying corn masa flour with folic acid could prevent birth defects, March of Dimes says

June 16, 2011
Fortifying corn masa flour with the B vitamin folic acid could prevent more serious birth defects of the brain and spine in the Hispanic community, according to a March of Dimes commentary published in the American Journal ...

Folic acid given to mother rats protects offspring from colon cancer

May 26, 2011
Folic acid supplements given to pregnant and breast-feeding rats reduced the rate of colon cancer in their offspring by 64 per cent, a new study has found.

Recommended for you

New understanding of how muscles work

August 23, 2017
Muscle malfunctions may be as simple as a slight strain after exercise or as serious as heart failure and muscular dystrophy. A new technique developed at McGill now makes it possible to look much more closely at how sarcomeres, ...

Scientists find RNA with special role in nerve healing process

August 22, 2017
Scientists may have identified a new opening to intervene in the process of healing peripheral nerve damage with the discovery that an "anti-sense" RNA (AS-RNA) is expressed when nerves are injured. Their experiments in mice ...

Mouse model of human immune system inadequate for stem cell studies

August 22, 2017
A type of mouse widely used to assess how the human immune system responds to transplanted stem cells does not reflect what is likely to occur in patients, according to a study by researchers at the Stanford University School ...

Researchers offer new targets for drugs against fatty liver disease and liver cancer

August 22, 2017
There may no silver bullet for treating liver cancer or fatty liver disease, but knowing the right targets will help scientists develop the most effective treatments. Researchers in Sweden have just identified a number of ...

Link between cells associated with aging and bone loss

August 21, 2017
Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. ...

Bio-inspired materials give boost to regenerative medicine

August 18, 2017
What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.