a) Where and how are superoxide radicals generated? b) Do they have constructive, destructive or both functions?

a) Where and how are superoxide radicals generated? b) Do they have constructive, destructive or both functions?

A free radical is “an atom, molecule, or molecular fragment that has one or more unpaired electrons” which leads to its “high reactivity” and “pro-oxidant activity” (1). If these radicals are oxygen-based, they are reactive oxygen species (ROS); if nitrogen based then reactive nitrogen species (RNS) (1). Oxygen is the terminal electron acceptor in mitochondria for energy production. However, high levels of intracellular oxygen can be harmful to cell as oxygen molecules can become incomplely reduced, termed reactive oxygen species. These ROS include superoxide radical ion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH-) (2).

ROS reactions take place in multiple locations within a cell: the plasma membrane, nucleus, vacuole, or mitochondria (1). When these processes lead to excessive ROS then this is termed oxidative stress (1). Processes that contribute to ROS include (1):

1. Environmental pollution, including chemical, drugs, radiation, pollution.
2. Exposure to very high levels of oxygen
3. Normal physiological responses
   1. Oxidative phosphorylation in mitochondria
   2. Immune defense
   3. with liver metabolism (peroxisomes and cytochrome P450).

Superoxide radicals may be formed when molecular O2 has a reaction, and may be seen with CONSTRUCTIVE reactions such as with (1):

• tetrahydrofolate
• with the electron transport chain
• Cytochrome P450 enzymes
• white blood cells

With excessive reactions or toxins present, superoxide radicals can react to form secondary reactive substances like  hydrogen peroxide (H2O2) and hydroxyl radical (OH-) (1). Specifically, the hydroxyl radical can be harmful as it will react quickly and definitely with surrounding molecules, including DNA molecules (1). These harmful reactions can lead to DNA damage or protein degradation that can impair cellular function and lead to disease state.s 

Sources:

1/ Gropper et al. Advanced Nutrition in Human Metabolism. 7th Ed. Cengage. 2018.

2/ Thorpe, G.W., Reodica, M., Davies, M.J., Heeren, G., Jarolim, S., Pillay, B., Breitenbach, M., Higgins, V.J., Dawes, I.W., 2013. Superoxide radicals have a protective role during H 2 O 2 stress. Molecular Biology of the Cell 24, 2876–2884. https://doi.org/10.1091/mbc.e13-01-0052 (Links to an external site.)Links to an external site.