Why Free Radicals Are Harmful

Why Free Radicals Are Harmful

Why free radicals are bad

A free radical is a molecule that contains an unpaired electron. Although many types of free radicals exist, all of them are derived from the same free radical, the superoxide anion radical (·O2⁻). Mitochondria are cellular organelles that produce superoxide anion radicals as byproducts during energy production, and they are the power plant of the cell. Ingested food is degraded to simple nutrients, such as glucose, amino acids, and fatty acids, in the intestines. Glucose is converted to energy in mitochondria, where electrons are generated. Oxygen serves as an electron acceptor in mitochondria. With the aid of enzymes, each oxygen molecule can accept four electrons and convert to a water molecule. Therefore, oxygen is essential for energy production in mitochondria. This is why we need to breathe—in order to bring oxygen molecules to mitochondria for energy production in every cell in the body.

Incidentally, electrons generated during energy production can stray or become lost in the mitochondria, similar to the power lost when electricity is transported through high-voltage power lines in our communities. The stray or lost electron can react with oxygen molecules to produce superoxide anion radicals, which are the origins of all other free radicals in the cell. All other free radicals, including peroxide and hydroxyl radicals, are derived from superoxide anion radicals. To circumvent this potential free radical problem, mitochondria are equipped with two powerful enzymes, superoxide dismutase and catalase. The former converts superoxide anion radicals to hydrogen peroxide, while the latter converts hydrogen peroxide to water and oxygen.

In small amounts, hydrogen peroxide works as a cellular messenger. Hydrogen peroxide can enter a cell nucleus and promote expression of

antioxidant-related genes and boost production of antioxidant enzymes. Here, hydrogen peroxide acts as part of the body's natural defense mechanism against free radical–induced oxidative damage to organs and tissues.

On the other hand, in large amounts, hydrogen peroxide can be harmful to the body. Excessive hydrogen peroxide can react with metal ions, such as ferrous ions, in the cell, which is called a "Fenton reaction."

Fe+3 + H2O2 → Fe+3 + OH⁻ + ·OH

The Fenton reaction generates hydroxyl radicals (OH⁻), the most potent and harmful free radicals known to humankind. Hydroxyl radicals are the strongest oxidants and possess an extremely high reactivity toward biomolecules, such as lipids, proteins, or nucleic acids. They work by stealing electrons from these biomolecules. Losing electrons precipitates structural instability in proteins, lipids, and DNA and eventually causes the structural collapse of these biomolecules, which then generates even more free radicals. This is known as the chain reaction of a free radical. The chain reaction initiated by hydroxyl radicals and the like can lead to oxidative damage to organs and tissues. Oxidative damage is the major cause of chronic diseases, including cardiovascular disease, diabetes, Alzheimer's disease, heart disease, chronic inflammation, atherosclerosis, and cancers.

Author's note: Using electron spin resonance spectroscopy, I demonstrated experimentally for the first time the existence of hydroxyl radicals in a biological system when I was a graduate student in Honolulu, Hawai‘i. In the next chapter, I will briefly present a personal account of my hunt for the hydroxyl radical.