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Biochemistry

Another use

A new mechanism through which vitamin C combats free radicals is identified

Consumed (with or without any scientific base) by anyone who wants to avoid a cold, vitamin C is an ally against free radicals, molecules that circulate through the organism and can cause damage to compounds that they come across, such as DNA or proteins essential for the body’s working. This microscopic war could contribute to the death of cells and be the origin of aging and of cancer. A research group from the University of São Paulo (USP) and the Butantan Institute have just finished revealing a new function of vitamin C as an antioxidant (action against free radicals). The study, published in the scientific magazine PNAS in partnership with the chemist Ohara Augusto, makes up part of the doctorate thesis of Gisele Monteiro, from the laboratory headed by Luis Eduardo Soares Netto, at USP’s Biosciences Institute. The team is a member of the Millennium Redoxoma Institute, a network that brings together around 200 Brazilian researchers who intend to understand and control the oxidation processes in cells. The program entitled, Millennium Institutes, from the Ministry of Science and Technology, was created to sponsor scientific research of excellence in strategic areas for the country’s development.

Linus Pauling, the 1954 winner of the Nobel Prize in Chemistry, who dedicated a large part of his career to vitamin C, had already suspected it of having antioxidant properties. But he did not know the chemical reaction details, which were discovered little by little. Ascorbate, the main component of vitamin C, can react directly with hydrogen peroxide (oxygenated water) and transform it into molecules of water, harmless to the organism, instead of dangerous free radicals. The new discovery is the manner in which ascorbate combats the formation of these potentially dangerous molecules: as well as participating directly in reactions, it also recycles molecules called peroxiredoxins, which function as catalysts accelerating the transformation of hydrogen peroxide into water.

These antioxidant catalysts lose electrons in the reaction with hydrogen peroxide, but they continue available in the cell. It is enough for them to gain electrons once more and they are ready to re-begin recycling. But if there is little peroxiredoxin or if the recycling does not occur at an adequate speed, the reaction is arrested, like a sandglass that is not turned over and stops counting time. The hydrogen peroxide is a by-product of cellular respiration, therefore it exists in all cells. In order to minimize the toxic effect, adequate concentrations of the molecules are needed to transform them into water. The ascorbate, just like the molecules called thiols, constantly donate electrons to the peroxiredoxin and in this way they develop the capacity to act as antioxidants.

“To discover that vitamin C acts in conjunction with other antioxidants broke a paradigm”, says Netto. Before this, it had been believed that the reaction depended exclusively on the molecules called thiols. But the researcher does not recommend running out to buy vitamins or to drink orange juice. “Preliminary data suggests that the system is already working at the maximum”, he explains. It is like the gearing of a clock that functions perfectly – a watchmaker could attempt to add on a piece, but, if there were no place for him to fit it, it would not contribute to the machine’s performance.

Universal function
The work of the group headed by professor Netto did not just reveal the new function of ascorbate, but also showed that the reaction is not exclusive to humans. It also occurs in rats, plants, drosophila and bacteria. The protozoa Plasmodium falciparum and Trypanosoma cruzi, responsible for causing malaria and Chagas’ illness respectively, appear to make use of vitamin C in human blood to protect them from oxidative stress with which the host defends itself: the defensive cells surround the parasite and bombard it with free radicals, with lethal effect. In order to defend itself, the microorganism needs an efficient system to combat the free radicals. The discovery is a first step in understanding the mechanism, but does not as yet serve as a base for pharmacological advances against these illnesses. “Perhaps it might be possible to inhibit some specific protein of the parasite, which would turn it, this way, more susceptible to the cell’s defense”, speculated the biologist.

It is already an impressive feat to observe chemical reactions, invisible to the eyes of non-specialists. But the researchers are not content with this: at the end of her doctorate thesis, Gisele managed to manipulate the proteins and in this manner interfere in the reaction. Two forms of peroxiredoxins exist in the organism, but the ascorbate only recycles one of them. Gisele altered the chemical structure of the protein that does not interact with the vitamin C and managed to create an affinity – now she knows what causes this attraction.

The results represent an advance in the understanding of the processes that combat free radicals. Since it was a technically difficult study, it was the final part of Gisele’s thesis, but it went well and became the central part of her work, which she is now continuing to explore in her post-doctorate studies. The biochemist wants to know what is the biological relevance of vitamin C in antioxidant reactions, which she, up until now, has only examined in laboratory flasks. Could it be that in live animals the ascorbate competes with the thiols? “Now that the puzzle has been solved, other doors for investigation are opening up”, celebrate Netto.

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