Reactive Oxygen Species and Lipid Peroxidation

Reactive oxygen species (ROS) are highly reactive compounds, which is making them very dangerous in certain situations. They are mostly formed from O2 molecules in the mitochondrial electron transport chain1. When O2 molecules become reactive species, such as hydrogen peroxide (H2O2) or superoxide (O2), they might be counted as stable compounds. Unfortunately, they might become highly reactive oxygen species (hROS) such as hydroxyl radicals (OH.), with the presence of transition metal ions (Fe+2)2.

Figure 1: Explanation of O2’s electronic spin state.

O2 in the atmosphere is not highly reactive and thus does not react with organisms including us. The reason behind this is the O2 in the atmosphere has two unpaired electrons that have parallel spin states as shown in figure3. So, O2 cannot react with compounds except they also have two parallel spin states which are not quite observable. Due to two parallel spin states, reduction of O2, with electrons applied one by one. These electron additions make the O2 molecule a reactive specie.

Figure 2: Pathway of reduction of O2.

These reactions lead to cell injury or death. That is why oxidative stress is related to aging. Two things are accommodated with human aging. The decrease in the molecular antioxidants and increased amount of products that are derived by oxidation of the biological compounds4. The excess amount of these reactive species can lead to certain disorders by causing damage to lipids, proteins, or DNA5. Due to this reactivity, cellular membranes are undesirably open to ROS damage. Their high polyunsaturated fatty acid formation led to a chain reaction loop which is called “lipid peroxidation”5. Lipid peroxidation is dependent on the peroxide concentrations, by other means, how strong is the oxidative stress in the system. When the membranes are exposed to this stress, lipids (mostly unsaturated ones) are attacked by these reactive radicals and oxidized into lipid peroxides6. Lipid peroxidation is related to several critical diseases such as cancer, diabetes, acute lung injury, and Alzheimer’s disease7.

Figure 3: Steps of lipid peroxidation8 (without enzyme).

The main point of this reaction is that it has a loop effect. Lipid peroxidation starts with the initiation process. In this part, the free radicals are generated in order to become highly reactive against lipids. Fe+2 is also involved as a transition ion during the initiation part. The second stage is the propagation stage. This stage is the most important and dangerous one, due to having a cycle effect. Radicals are reacting with new substrates and generate new radical compounds. You can imagine this step by each newly generated radical lipid to lipid jump in the cell membrane. During each jump, the affected lipid remains in the distributed form, lipid peroxide. And the generated fatty acid radical continues to jump onto the next lipid compound. If it is not stopped with the termination process, this cycle continues and leads the cell death. The termination process occurs with either the presence of antioxidants or other radicals.

The ROS and antioxidant interaction are very important for controlling the production of ROS and stopping the lipid peroxidation reaction in the termination process. Antioxidants can be simply defined as chain-breaking antioxidant inhibitors of lipid peroxidation9. Most antioxidants play a role in interacting with the free radicals and taking their high reactivity Also, they might be raising the levels of antioxidant defences9. Their actions can be extended as removing O2 (as it is the main source of ROS), inhibiting ROS formation, and binding to the transition metal ions that are used in ROS generation10.

 To sum up, it is interesting that the oxygen molecule is not reactive at all until it enters the organism’s system. Oxygen’s natural spin state is distributed and changed with electron addition leads an absurd level of reactive species. Even though these reactive species play important roles in certain systems, sometimes they can play their role as the opposite of benefit. Understanding the chemical reactions behind these interactions and analyzing them plays a huge role in both the food and medicine industries. New methods for preventing these reactions or manipulating them are continuing to develop. It’s not a surprising thing when it is thought about the relationship between aging, diseases, and ROS.

References:

  1. Liu Y, Fiskum G, Schubert D. Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem. 2002;80(5):780-787. doi:10.1046/j.0022-3042.2002.00744.x
  2. Freinbichler W, Colivicchi MA, Stefanini C, et al. Highly reactive oxygen species: Detection, formation, and possible functions. Cell Mol Life Sci. 2011;68(12):2067-2079. doi:10.1007/s00018-011-0682-x
  3. Fridovich I. Fundamental aspects of reactive oxygen species, or what’s the matter with oxygen? Ann N Y Acad Sci. 1999;893:13-18. doi:10.1111/j.1749-6632.1999.tb07814.x
  4. Repetto M, Semprine J, Boveris A. Lipid Peroxidation: Chemical Mechanism, Biological Implications and Analytical Determination. Lipid Peroxidation. Published online August 29, 2012. doi:10.5772/45943
  5. Su LJ, Zhang JH, Gomez H, et al. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid Med Cell Longev. 2019;2019. doi:10.1155/2019/5080843
  6. Halliwell B, Chirico S. Lipid peroxidation: significance and its mechanism. Am J Clin Nutr. 1993;57(February):715-725.
  7. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: Mechanisms and analysis. Chem Rev. 2011;111(10):5944-5972. doi:10.1021/cr200084z
  8. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017;482(3):419-425. doi:10.1016/j.bbrc.2016.10.086
  9. Halliwell B, Aeschbach R, Löliger J, Aruoma OI. The characterization of antioxidants. Food Chem Toxicol. 1995;33(7):601-617. doi:10.1016/0278-6915(95)00024-V
  10. Halliwell B. Antioxidants: The Basics—What They Are and How to. Antioxidants Dis Mech Ther Antioxidants Dis Mech Ther Strateg. 1996;38:3.

Figure References:

  1. Fridovich I. Fundamental aspects of reactive oxygen species, or what’s the matter with oxygen? Ann N Y Acad Sci. 1999;893:13-18. doi:10.1111/j.1749-6632.1999.tb07814.x
  2. Fridovich I. Fundamental aspects of reactive oxygen species, or what’s the matter with oxygen? Ann N Y Acad Sci. 1999;893:13-18. doi:10.1111/j.1749-6632.1999.tb07814.x
  3. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017;482(3):419-425. doi:10.1016/j.bbrc.2016.10.086

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