More on Free Radicals and Oxidative Damage
Free radicals are cellular renegades; they wreak havoc by damaging DNA, altering biochemical compounds, corroding cell membranes and killing cells outright. Such molecular mayhem, scientists increasingly believe, plays a major role in the development of ailments like cancer, heart or lung disease and cataracts. Many researchers are convinced that the cumulative effects of free radicals also underlie the gradual deterioration that is the hallmark of aging in all individuals, healthy as well as sick.
-TIME, April 6, 1992
What are free radicals - a review. Atoms consist of the positively charged nucleus and negatively charged electrons. Electrons orbit around the nucleus in pairs and each pair has its own region of space. When an electron from a pair is removed, the molecule becomes very unstable and very reactive. A free radical is any chemical species, capable of independent (although extremely short) existence with one or more unpaired electrons. Free radicals frantically seek electrons in order to pair their unpaired electrons. Because most of the molecules in our body do not have unpaired electrons, free radicals steal electrons from normal molecules. This process is called oxidation.
Free radicals cause a chain reaction of oxidation. The speed at which these radicals, such as the hydroxyl radical, can steal electrons is incredible - one billionth of a second! Other common free radicals have very short half-lives from tiny fractions of a second to less than ten seconds. These radicals will attack the first molecule in its path - fat, protein, DNA, sugar. The newly damaged molecules unfortunately become free radicals (kind of like getting bitten by a vampire). These free radicals attack other molecules starting a chain-reaction!
Oxidation causes physiologic damage. Free radicals are part of life. Our immune system produces free radicals to fight invading bacteria and viruses and cells use free radicals to communicate with each other. When produced in large quantities, however, they can be extremely damaging. Free radical oxidative damage has been implicated in almost every major chronic disease. Aging, disease, physical and emotional stress, UV radiation, strenuous exercise, smoking and diet increase the production of free radicals. Lipids, sugars and enzymes and other proteins such as DNA that are oxidized cannot perform their normal function and may even become harmful. For example, damaged DNA may provide the wrong genetic code leading to unregulated protein synthesis and/or cell growth which results in cancer.
Lipid material in our body plays critical role. Our body contains lipid material or fat. Despite popular myths, lipid material plays vital roles in our body. Take cell membranes for example. To function properly, the membrane must be fluid. This means that its constituents must be able to move around freely.
What makes and keeps membranes fluid is the polyunsaturated fatty acid (PUFA) side chains in the membrane lipids. PUFA, however, are very susceptible to free radical attack (oxidation), which can start lipid peroxidation. A free radical can pull off a hydrogen atom (with its only electron) from polyunsaturated fatty acid side chains. As a result, the fatty acid has now an unpaired electron and becomes itself a free radical called peroxyl radical. It can then attack another fatty acid setting off a very destructive chain reaction. In theory, oxidation of a single lipid molecule by a one radical could start a chain reaction that would destroy all lipid material with devastating effects. Peroxyl radicals attack not only other lipid molecules but also proteins, DNA, sugars, hormones etc.
The survival of the cell depends on the integrity of its membrane. As we discussed above, the membrane must be fluid. This requires that the polyunsaturated fatty acid side chains attached to the membrane lipids must be protected from oxidation. Oxidized fatty acid chains are more hydrophilic than non-oxidized ones and seek to migrate to the surface of the membrane to interact with water. This can disrupt the membrane structure and destroy its fluidity. The membrane becomes leaky - a death sentence for the cell.
Unfortunately, polyunsaturated fatty acid side chains are easily attacked by radicals and generate highly reactive peroxyl radicals. Unless stopped, this whole process is repeated over and over as a chain reaction until all lipids go rancid.
Examples of free radicals and oxidizing compounds.
Free Radicals:
The hydroxyl radical is the leader of the pack. It is the most reactive oxygen radical known to chemistry. It is produced from water exposed to X-rays or gamma-rays, or from hydrogen peroxide present in our body. - Superoxide radical is produced from oxygen when an electron is attached.
- Nitric oxide and nitrogen dioxide. Nitric oxide is produced in our body. Nitrogen dioxide is found in polluted air and smoke. The vascular endothelial cells which form the lining of our blood vessels, the phagocytes which are part of our immune system and some brain cells also produce nitric oxide.
Oxidizing compounds: Most scientists group oxidizing compounds with free radicals. These are compounds that, although not free radicals, they are strong oxidants or can be converted easily to free radicals.
Some examples include:
- Hydrogen peroxide can make the extremely damaging hydroxyl radical. Injury or hemolysis (breakdown of our red blood cells) releases unbound iron, which promotes the conversion; UV radiation does the same.
- Singlet oxygen is an extremely reactive form of the same oxygen in the air we breath. Oxygen has two unpaired electrons arranged in such a way that oxidizes other molecules very slowly. If the electrons are rearranged, oxygen is converted to singlet oxygen. Light and compounds sensitive to light produce singlet oxygen.
- Ozone - At the stratosphere, ozone provides a protective shield against the harmful UV rays. At ground level, ozone causes major oxidation.
Free radicals are part of life!
- We consume approximately 3.5 kilograms of oxygen every day
- 2.8 percent of the oxygen is not properly used and forms free radicals
- Several kilograms of peroxides (harmful oxidized lipids) are produced in our body every year
Life is an incurable disease.
- Cawley, 1656