Evolution of Antioxidant Defense Mechanism

Organisms have evolved various antioxidation mechanisms to eliminate ROS and avoid oxidative destruction. In general terms, an antioxidant is anything which can prevent or inhibit oxidation. This can be achieved by preventing the generation of ROS, or by inactivating ROS. Antioxidants can be classified in several ways, for instance, endogenous/exogenous or mechanism of action etc. In this section, we classified antioxidants by the mechanism of action.

PreventionProtein binding/inactivation of metal ionsTransferrin,ferritin,caeruloplasmin,albumin
Enzymatic diversion/ neutralisationSpecific channeling of ROS into harmless productsSuperoxidase, dismutase,catalase,glutathione peroxidase
ScavengingSacrificial interaction with ROS by expendable (replaceable or recycable) substratesAscorbic acid,alpha tocopherol ,uric acid,billurubine,glutathione
QuenchingAbsorption of electrons and/or energyAlpha tocopherol,beta carotene

The first antioxidant mechanisms were probably simple physical barriers. Intracellular sequestration of photo-sensitizing pigments such as chlorophyll, development of UV screens and compartmentalization of vulnerable cellular components would serve to protect against the production and action of ROS. The first membrane defense is likely to have been the coating of a simple polymer would have bound extracellular metals ions such as Fe+2 effectively absorbing the subsequent ROS- action and protecting cell membrane. Because of the increased oxidized, soluble forms of cations, they shift into the cell and lead to requiring more specific antioxidant mechanism.

As mentioned before content hydroxyl radical(•OH) is the most reactive ROS and mechanisms which prevented •OH production were favored. Other strategies which diversion of H2O2 to harmless H20, dismutation of superoxide ( •O2-), scavenging of ROS and quenching of excess energy also favored.

Various Antioxidant mechanism

Binding iron and copper prevents •OH production via Fenton Chemistry. This strategy is highly effective and is still used in biological systems for instance transferrin, ferritin, and caeruloplasmin which keeps the concentration of free iron and copper in human plasma extremely low levels

Haber-Weiss Reaction
Fenton and Haber-Weiss Reaction

Enzymes which catalyze the removal of H2O2 include the catalases and peroxidases. These antioxidants are found in almost all aerobic organisms.


In animals, glutathione peroxidase(GPx) acts in cooperation with catalase in the removal of H2O2. The oxidized form of glutathione (GSSG) is reduced and required glutathione reductase enzymes to recycle.

glutathione system
Glutathione peroxidase and glutathione reductase

The enzyme which dismutates superoxide ( •O2-) is Superoxide Dismutase(SOD) also play a role as an antioxidant. Manganese has superoxide dismutase-like activity when it accumulates inside cells and the first SOD may have simply used this property.

Superoxide Dismutase
Superoxide Dismutase

Scavengers include the water-soluble ascorbic acid (vitamin C) and the lipid soluble tocotrienols (vitamin E) are required to eliminate some ROS like singlet oxygen which produced in the plants when harvesting light. To prevent the formation of singlet oxygen and the protect these organelles from excessive energy, an antioxidant mechanism to absorb or quench energy was needed. Carotenoids are very effective quenching antioxidants and are vital components of membranes surrounding chloroplasts.

Chemical compound of Vitamin C
Chemical compound of Vitamin C
Chemical compound of Vitamin E
Chemical compound of Vitamin E

Various types of antioxidant have developed and these reflect different selection pressures over time. Different forms have developed for the same purpose and some species-specific configurations are found. For instance, SODs and peroxidase are widespread but in animals, GPx is also important. Quenching antioxidants are restricted to light-harvesting plants. Tocopherols are also manufactured only in plants but are needed by animals. Ascorbic acid is an essential antioxidant but interestingly cannot be synthesized in a few species, including humans.

Sources and further reading

1)Benzie IF. Evolution of antioxidant defense mechanisms. Eur J Nutr. 2000 Apr;39(2):53-61.

2)Rodriguez R, Redman R. Balancing the generation and elimination of reactive oxygen species. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3175-6.

3)Bilinski T. Oxygen toxicity and microbial evolution. Biosystems.1991;24(4):305-12

4)Fenton reaction – Controversy concerning the chemistry – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Basic-free-radical-mechanisms-for-the-Fenton-and-Haber-Weiss-reaction-43-66_fig2_279937336

[accessed 22 Jan 2019]

5)Chapter 3: Introduction to oxidative cytotoxicity and cellular defense mechanisms – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Structure-and-functional-basis-of-catalase-enzyme_fig4_271644390

[accessed 22 Jan 2019]

6)Weydert CJ, Cullen JJ. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc. 2010 Jan;5(1):51-66. doi: 10.1038/nprot.2009.197.


8)Halliwell, Barry & M.C. Gutteridge, John. (1999). Free Radicals In Biology And Medicine. Journal of Free Radicals in Biology & Medicine. 1. 331–332. 10.1016/0748-5514(85)90140-0.

1 Comment

Gil Shead · June 29, 2019 at 2:02 am

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