A study performed by researchers from the Institute for Advanced Chemistry of Catalonia (IQAC) from the Spanish National Research Council (CSIC) in collaboration with Tsinghua University at Beijing, University of Pennsylvania, and Purdue University at the United States, have pointed out that cysteine disulfides have a very active role in the formation of a potent antioxidant compounds. This research, published in the journal Proceedings of the National Academy of Science, provide new insight into the antioxidant effect of cysteine disulfide compounds, as well as the formation of sulfenic acid as a potent antioxidant.
As scientists reveal in this work, cysteine disulfide, one of the antioxidants that naturally forms in the cell, becomes into a much more potent antioxidant, sulfenic acid, when it reacts with a hydroxyl radical, which is one of the most oxidative molecules in the cell.
Natural molecules of the human organism
The antioxidants are substances like vitamin C, E or glutathione, which are be able of preventing or slowing down the oxidation of other molecules such as lipids, proteins or nucleic acids. The main role of antioxidant substances is to protect cells from the damaging effect of free radicals, which are molecules responsible for altering living organisms that accelerate ageing and contribute to the development of diseases, such as cancer, parkinson’s or alzheimer’s, among others.
“Free radicals and reactive oxygen species (ROS) are generated naturally in cellular metabolism and do not always play a negative role, since they also intervene in correct cellular communication. However, as in all biological systems, cells also need to maintain a balance between the production of free radicals and their elimination”, explains Ramon Crehuet, researcher at the IQAC-CSIC. “Consequently, the function of antioxidant compounds is very important, since they prevent the increase of oxidative activity inside the cell, which causes a structural and functional change in it, accelerating its ageing and favoring cell death”, clarifies Crehuet.
One of the main amino acids in our body, cysteine, is a precursor of antioxidant species at the cellular level and its disulfide derivative plays an important role in the structure and function of proteins, enzymes, and insulin, for example. The purpose of the present study was to investigate how the hydroxyl radical (OH), one of the most oxidative species in our body, reacts with disulfides of the amino acid cysteine.
One of the main conclusions is that, by reacting with the hydroxyl radical, cysteine disulfide becomes into a more powerful antioxidant, sulfenic acid (- SOH). “These results help us to gain insight the role of these antioxidant compounds and to understand a new line of defense against free radicals,” explains another co-author of the study, Josep M. Anglada, from IQAC-CSIC.
The basic reaction mechanisms between the hydroxyl radical (OH) and the molecules with disulfide bonds had been previously determined using simpler models. The research carried out in this work is based on a combination of experimental, mainly based on mass spectroscopy in order to determine which products are formed in the reaction and in what proportion, and in the application of theoretical chemistry studies, especially quantum mechanics and kinetics. “These studies allow us to understand why some products are formed and not others, and also allow us to predict how the hydroxyl radical will behave against other disulfides or in different environments”, concludes Anglada.
Two-step reaction mechanism reveals new antioxidant capability of cysteine disulfide against hydroxyl radical attack. Sarju Adhikari, Ramon Crehuet, Josep M. Anglada, Joseph S. Francisco, and Yu Xia. Proceedings of the national Academy of Sciences, of the United States of America. DOI: https://www.pnas.org/lookup/doi/10.1073/pnas.2006639117