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Lack of key enzyme in the metabolism of folic acid leads to birth defects
Date:1/17/2013

AUSTIN, Texas 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 spina bifida and anencephaly, 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 Proceedings of the National Academy of Sciences (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 model system 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 mut
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Contact: Dean Appling, professor
dappling@austin.utexas.edu
512-471-4796
University of Texas at Austin
Source:Eurekalert

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