Folic acid , or folate, or vitamin B 9, it is necessary for the synthesis of nucleic acids – without it, nitrogenous bases will not be obtained, the very genetic letters that form the sequence of DNA and RNA. Of course, folate deficiency is fraught with serious consequences. These consequences can be especially strong if folic acid deficiency occurs during pregnancy: a developing embryo will develop developmental pathologies, mainly in the nervous system and heart. Many countries now have government programs to fortify foods with folate. Knowing how much folate is needed, many on their own initiative begin to take it in one form or another, believing that even if it turns out to be too much, nothing bad will still happen.
There is evidence that if there is too much folic acid, the body has the same problems as when it is too low. However, according to a recent letter to Cell Discovery from Baylor College of Medicine, such work is still scarce. As a result, we know little about what mechanism works here, i.e. how exactly an excess of folate damages cells. The researchers tried to at least partially correct the situation. In experiments with mice, they fed the rodents three different diets: in one case, the folate in the food was not enough compared to what the mouse usually needs, in the other it was just right, and in the third case there was already too much folate. The mice were kept on each diet for several months. The animals were then mated with partners who ingested normal amounts of folate. The offspring’s DNA was compared to the parent’s DNA to see if the children had mutations that the parents did not.
In general, such mutations look like this. Some genetic defects appear in the germ cells of the father and mother, which are not found in the cells of other organs, and the embryo itself can acquire original mutations. But offspring in which one parent got too little folate had twice as many such mutations. And in the offspring, in which one of the parents got too much folate, there were 1.8 times more of these mutations. That is, both a lack and an excess of folic acid led to the fact that more defects appeared in the DNA.
All cells have a set of tools designed to repair (repair) DNA. But these tools are encoded in the DNA itself. The genes that encode them can function more or less actively. If the repair genes are inactive, the repair proteins will be missing. An excess of folate only affects the activity of repair genes. Folate is required not only for the synthesis of nitrogenous bases, but is also involved in other cellular processes. Researchers have found that with an excess of folic acid, many methyl marks appear on the DNA of the repair genes. This is one of the common mechanisms to regulate gene activity and usually DNA methylation means that it is inactive here. Molecular machines that read genetic information bypass the methylated regions.
In other words, with an excess of folic acid, DNA repair mechanisms begin to work worse, and therefore the number of mutations increases. The details still need to be clarified: We need to figure out exactly when excess folate acts that way, how exactly it stimulates DNA methylation enzymes, etc. However, even without such details, new data once again tell us that even with a lot of useful substances it is necessary to know the measure.
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