8.1: Introduction to Free Radicals and Antioxidants
- Page ID
- 21148
Learning Objectives
- Describe free radicals.
- Identify various free radical detoxifying enzymes and antioxidants.
- Explain oxidative stress and identify diseases associated with oxidative stress.
In mainstream advertising you may have heard that antioxidants can extend your life by preventing disease and slowing the aging process. But what are antioxidants? Where do you get them? And how do they work in the body? After reading this chapter you will be able to answer these questions, and your new knowledge will assist you in making dietary decisions to optimize your health.
Keep in mind as you read...there is no scientific evidence that antioxidants singularly provide bodily benefits, but there is evidence that certain benefits are achieved by ingesting antioxidants as part of a balanced, healthy, nutrient-rich diet. This is to say antioxidants may go a long way toward preventing damage, but other nutrients are necessary to repair damage and sustain health. No one nutrient acts alone!
Oxidation
Antioxidants are compounds that protect cells from damage caused by oxidation. But what is oxidation? Oxidation is a chemical reaction in which atoms lose electrons. Atoms have a nucleus (central core) which is positively charged. Orbiting around the nucleus are electrons which are negatively charged. The opposite attraction between the positively charged nucleus and negatively charged electrons keeps an atom stable. However, during metabolic reactions, atoms exchange electrons. Oxidation is the loss of electrons from an atom. Conversely, reduction is the gain of electrons by an atom. Oxidation and reduction usually occur together as an exchange reaction. One way to remember the difference between oxidation and reduction in the exchange reaction is to remember "OIL RIG":
- OIL = Oxidation Is Loss of electrons
- RIG = Reduction Is Gaining of electrons
Free Radicals
Oxidation sometimes results in the formation of free radicals. Remember those electrons that are orbiting the nucleus of an atom? Well those electrons contain energy; however, this energy is not always stable. The stability depends on the number of electrons that are within an atom. Atoms are more stable when their electrons orbit in pairs. An atom with an odd number of electrons must have an unpaired electron. When oxygen (a molecule with two atoms) has one unpaired electron it is known as superoxide (Figure \(\PageIndex{1}\)). Atoms and molecules such as superoxide that have unpaired electrons are called free radicals (Figure \(\PageIndex{2}\)). The unpaired electron in free radicals makes the atom or molecule unstable.
Electrons in atoms "hate" not existing in pairs. An atom with an unpaired electron (a free radical) wants to become stable again, so it quickly seeks out another electron to "steal" from another atom or molecule. The instability of free radicals is what poses a threat to macromolecules such as DNA, RNA, proteins, and fatty acids. Free radicals can cause chain reactions that ultimately damage cells. For example, a free radical may react with a fatty acid and steal one of its electrons. The fatty acid then becomes a free radical that can react with another fatty acid nearby. As this chain reaction continues, the permeability and fluidity of cell membranes changes, proteins in cell membranes experience decreased activity, and receptor proteins undergo changes in structure that either alter or stop their function. If receptor proteins designed to react to insulin levels undergo a structural change it can negatively effect glucose uptake.
Free radical reactions can continue unchecked unless stopped by a defense mechanism.
The Body’s Defense
Free radical development is unavoidable, but human bodies have adapted by setting up and maintaining defense mechanisms that reduce their impact. The body’s two major defense systems are free radical detoxifying enzymes and antioxidants. Free radical detoxifying enzyme systems are responsible for protecting the insides of cells from free radical damage. An antioxidant is any molecule that can block free radicals from stealing electrons; antioxidants act both inside and outside of cells.
Free Radical Detoxifying Enzymes
The three major enzyme systems and the chemical reactions they catalyze are:
- Superoxide Dismutases (SOD). These enzymes have either a manganese, copper, or zinc cofactor, which is essential for their free radical detoxifying activity. During SOD-mediated enzymatic catalysis, two superoxides are converted into hydrogen peroxide and oxygen. Hydrogen peroxide (H2O2) is still considered a free radical, but it is less reactive than some other free radicals (e.g., superoxide). SOD enzymes are one of the fastest enzymes known, and they are also inducible, meaning that the higher their exposure to superoxides, the greater their number and detoxifying activity.
- Catalase. This enzyme contains iron as a cofactor and converts hydrogen peroxide to water and oxygen, thereby finishing the detoxification reaction started by SOD. In cells, catalase enzymes are found in high numbers and continuously patrol for hydrogen peroxide molecules. Catalase is highly efficient and is capable of destroying millions of hydrogen peroxide molecules per second.
- Glutathione Peroxidases. The majority of enzymes within this family are dependent on the micronutrient selenium. Similar to catalase, these enzymes convert hydrogen peroxide to water and oxygen.
Antioxidants
Antioxidants are compounds that protect cells from damage caused by oxidation. Antioxidants are broadly classified as either hydrophilic (water soluble) or hydrophobic (lipid soluble), and this classification determines where they act in the body. Hydrophilic antioxidants act in the cytosol of cells or in extracellular fluids such as blood; hydrophobic antioxidants are largely responsible for protecting cell membranes from free radical damage. The body can synthesize some antioxidants, but others must be obtained from the diet.
Antioxidants the Body Synthesizes
There are two antioxidants that the body synthesizes. They are:
- Glutathione. This molecule is composed of three amino acids and is found in high concentrations in cells. Glutathione contains a sulfur group that can donate an electron to a free radical, thereby stabilizing it. After glutathione has lost its electron, it is regenerated enzymatically so that it can perform its antioxidant function once again.
- Uric Acid. This molecule is a metabolic intermediate in the breakdown of nucleotides such as adenine, which is found in DNA and RNA, among other macromolecules. It circulates at high concentrations in the blood and disables circulating free radicals. However, too high of a concentration in the blood can cause gout, a painful joint disorder.
Antioxidants Obtained from the Diet
There are many different antioxidants in food (Table \(\PageIndex{1}\)). Antioxidant vitamins (e.g., Vitamin E, Vitamin C) donate their electrons to free radicals to stabilize them. Antioxidant phytochemicals (e.g., beta-carotene and other carotenoids) may inhibit the oxidation of lipids or donate electrons. Antioxidant minerals act as cofactors within complex antioxidant enzyme systems (e.g., superoxide dismutases, catalase, glutathione peroxidases described earlier) to convert free radicals to less damaging substances that can be excreted.
| Antioxidant | Functions |
|---|---|
| Vitamin E | Protects cellular membranes, prevents glutathione depletion |
| Vitamin C | Protects DNA, RNA, proteins, and lipids, aids in regenerating vitamin E |
| Carotenoids | Free radical scavengers |
| Selenium | Cofactor of free radical detoxifying enzymes, maintains glutathione levels, aids in regeneration of vitamins C and E |
The Body’s Offense
While our bodies have acquired multiple defenses against free radicals, we also use free radicals to support its functions. For example, the immune system uses the cell-damaging properties of free radicals to kill pathogens. First, immune cells engulf an invader (such as a bacterium), then they expose it to free radicals such as hydrogen peroxide, which destroys its membrane. The invader is thus neutralized.
Free radicals are necessary for many other bodily functions as well. The thyroid gland synthesizes its own hydrogen peroxide, which is required for the production of thyroid hormone. Free radicals have been found to interact with proteins in cells to produce signaling molecules. The free radical nitric oxide has been found to help dilate blood vessels and act as a chemical messenger in the brain.
Sources of Free Radicals in the Environment
The body creates free radicals through the normal processes of metabolism (i.e., turning food into usable energy/ATP). When the amount of free radicals exceeds the body’s ability to eliminate or neutralize them, an oxidative imbalance results.
Substances and energy sources from the environment can add to or accelerate the production of free radicals within the body. Exposure to excessive sunlight, pollution, ozone, smoke, heavy metals, ionizing radiation, asbestos, and other toxic chemicals increase the amount of free radicals in the body. They do so by being free radicals themselves or by adding energy that provokes electrons to move between atoms. Excessive exposure to environmental sources of free radicals can contribute to disease by overwhelming the free radical detoxifying systems and those processes involved in repairing oxidative damage.
Oxidative Stress
Oxidative stress occurs when there is an imbalance between free radical production and their detoxification. Sustained oxidative tissue damage that can contribute to disease occurs only when free radical detoxification systems and repair systems are overwhelmed. Free radical-induced damage, when left unrepaired, destroys lipids, proteins, RNA, and DNA, and can contribute to disease. Oxidative stress has been implicated as a contributing factor to cancer, heart disease, arthritis, diabetes, kidney disease, Alzheimer’s disease, cataracts, Parkinson’s disease, and aging.
Key Takeaways
- Free radicals, unstable molecules with unpaired electrons, are an unavoidable byproduct of cellular metabolism.
- Free radicals can steal electrons from lipids, proteins, RNA, and DNA, causing them damage.
- The body has defenses against free radicals—free radical detoxifying enzymes and antioxidants.
- The body can synthesize some antioxidant molecules, but many are obtained from the diet.
- The body sometimes uses free radicals for beneficial functions such as killing pathogens.
- Oxidative stress is an imbalance between free radical production and detoxification and repair systems. It also plays an integral role in the development of many chronic diseases and in age-related decline of tissues.
- Excessive sunlight, pollution, ozone, smoke, heavy metals, radiation, asbestos, and other toxic chemicals increase the amount of free radicals in the body and can accelerate the progression of diseases in which oxidative stress is a contributing cause.