Despite these widespread implications, a significant link between peroxide and sulfide metabolism had yet to be elucidated until now. This improvement might change our insight of enzymatic mechanisms in humans and malaria causing pathogen, Plasmodium falciparum. Led by Professor Marcel Deponte, the research team revealed how peroxiredoxin 6-type peroxidases react with hydrosulfide, the anion of hydrogen sulfide, an interaction occurring at remarkable speeds.
The research underscores an interesting class of peroxiredoxin 6-type peroxidases found in humans and the malaria parasite. These unique enzymes are fundamentally important in degrading hydrogen peroxide. This unexpected finding leads to fascinating new biochemical questions and possibilities. What’s most impressive is how it highlights the evolutionary divergence between these organisms and highlights unexpected similarities in their metabolic pathways.
These surprising findings, published today in the journal Advanced Science, used the stopped-flow method to directly observe these rapid enzymatic reactions. Based on previous work, it was proposed that hydrosulfide might serve as a universal reducing agent for these enzymes. In contrast to classical physiological reducing agents, these enzymes usually do not respond to them.
Methodology and Findings
This allowed the research team to successfully produce the requisite peroxiredoxin 6-type enzymes. They first worked with benign strains of Escherichia coli and then performed purification steps. This combined approach in turn enabled a careful study of the enzymes catalytic cycle and how they interacted with hydrosulfide.
Lukas Lang and Laura Leiskau, the study’s first authors, explained the fast response of peroxiredoxin 6-type peroxidases to hydrosulfide. This dynamic, multi-step process ultimately converts hydrogen peroxide into water. It’s this reaction that forms hydrogen disulfide. Researchers suspect it is protective because of its role as a source of persulfides, which have protective functions.
“Our research showed that peroxiredoxin 6-type peroxidases in humans and the malaria parasite Plasmodium falciparum react extremely rapidly with hydrosulfide, the anion of hydrogen sulfide. As a result, hydrogen peroxide is reduced to water and hydrogen disulfide is formed as a potential source of persulfides. The latter are currently thought to have a protective function. Furthermore, we gained first insights into the intermediates of the unusual catalytic cycle of these enzymes,” – Laura Leiskau.
Implications of the Research
Knowing precisely how these enzymes work lays the groundwork for entirely new approaches to biochemistry and development of therapeutic targets that might one day help us defeat malaria. The results reveal dramatic evolutionary divergence between humans and malaria parasites. Yet, when they interact with hydrosulfide, both show strikingly similar enzymatic processes.
Professor Deponte expanded on these exciting findings. He pointed out that the reaction characteristics revealed in these two organisms may extend to other peroxiredoxin 6-type peroxidases.
“Humans and malaria parasites are evolutionarily unrelated and belong to completely different groups of eukaryotes. Since the results were highly comparable, we assume that hydrosulfide also reacts very quickly with other peroxiredoxin 6-type peroxidases,” – explains Deponte.
As we wrote previously, the study is consistent with emerging research. Together, these studies indicate that hydrogen sulfide might be used more broadly as a reducing agent in various biological systems.
“The idea of testing hydrogen sulfide or sulfides, which are found in all living organisms, as reducing agents gained momentum when, in 2024, two other research groups independently discovered that peroxiredoxin 6-type peroxidases can react with hydrogen selenide,” – Marcel Deponte.
Future Directions
This research is more than just fundamental science. It has the potential to inform the design of new therapies to treat other diseases, including malaria. Classification of Peroxiredoxin 6-type peroxidases Peroxiredoxin 6-type peroxidases are essential for cellular metabolism. Understanding their mechanisms might reveal new opportunities that can be targeted through drug development.
The ongoing research by Professor Deponte and his team promises to deepen our understanding of enzymatic functions and their significance in both human health and disease dynamics. By unraveling the complexities of these metabolic pathways, scientists may pave the way for innovative solutions to combat malaria and other oxidative stress-related conditions.