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The dark side of oxigen
How free radicals cause damage and disease?
Free radical damage may involve any cellular constituents.
These constituents include mitochondria, lysosomes, peroxisomes,
nuclear endoplasmic reticulum, and plasma membranes, as well
as sites within the cytosol. All are vital to the normal metabolic
functions of the cell.
Free radical damage culminates in cross-linkages, denaturation,
and inactivation. The genetic machinery of the cell may be damaged,
which is a major disorder in ionizing radiation. Damage to the
DNA molecule may result in mutagenesis and carcinogenesis (Floyd,
1982).
Oxygen plays a key role in the generation of free radicals and lipid peroxidation. Molecular oxygen is uniquely suited for free radical production because its two unpaired electrons cause the molecule to participate in redox reactions at the kinetic energy levels available in biological systems. Damage to intracellular membrane lipoprotein assemblies by oxidant free radicals can have profound adverse effects in the cell.
A detailed description of the process of lipid peroxidation of intracellular membranes will demonstrate how free radicals can adversely affect cellular health. The cell is a mass of protoplasm, the cytoplasm that contains a nucleus surrounded by a plasma membrane. The human body contains an estimated 100 trillion cells. Each cell contains such organelles as mitochondria, endoplasmic reticulum, ribosomes, Golgi complex, and lysosomes.
The mitochondria) function as the power plants of the cell and supply the required energy. The endoplasmic reticulum) transports the materials from one part of the cell to the next. The ribosomes) are the manufacturing site of protein compounds. The Golgi Complex "packages" cellular proteins, releasing them into units that can be used outside of the cell. The lysosomes) are membrane-enclosed bags of enzymes, sometimes referred to as the cell's digestive system. Thus each of these organelles are membrane-bound complex bodies concerned with the various metabolic functions of the cell.
The interior of these cells are in a continual state of movement and chemical change. The membranes surrounding these organelles are vital dynamic structures that are important in controlling the passage of nutrients and excretory products involved in cellular metabolism, and in the organization of cellular enzymes. Any physical, chemical, or biological agents affecting the intracellular membranes will influence the health of the cell, for better or for worse.
The structure, chemistry, and function of these membranes are extremely complex (Weissman and Claiborne, 1975). When destructive free radical molecules come in contact with these membranes, they can produce lipid peroxidation and membrane destruction (Tappel, 1973a, b; Tappel, Fletcher, and Deamer, 1973). The destruction of these membranes may result in a loss in the organization of cellular enzymes, a disturbance in the distribution of nutrients, and a dysfunction of cellular metabolism. This sequence of events is part of the degenerative disease process and the production or atherosclerosis.
Biological molecules can be raised to higher energy states by exposure to ionizing radiation and thereby become reactive. In this state, they are capable of transferring electrons to acceptors such as oxygen in order to generate free radicals Oxygen makes cells more sensitive to radiation. Oxygen reacts with the free radicals produced by radiation and may further enhance the destructive reactions with the molecules of the cell.
Biochemical reactions are generally characterized by specific, orderly reactions. However, free radicals react with little regard to selectivity. They can initiate a chain reaction which, even at very low concentrations, can cause serious toxic effects in biological systems (Yamazaki, 1977).
In radiation sickness, free radicals are of the utmost importance because it is through them that the indirect action of radiation takes place. Primary ion radical species then undergo transformations such as decarboxylation, deamination, and disulfide bond rupturing whereby deposition energy is transferred inter-or intra-molecularly with the formation of semi-stable neutral bioradicals. As a result, free radicals are capable of causing cancer, various chronic degenerative diseases, immunincompetence, and contribute greatly to the aging process.
Each free radical can destroy an enzyme or protein molecule or even an entire cell. The damage is actually even more extensive because each free radical usually generates a chain of free-radical reactions, resulting in thousands of free radicals being released to destroy body components.
Five basic types of damage caused by free radicals:
Source: (A key mechanism to understanding aging) Free Radicals Test & The Nutrition Superbook, The Antioxidants, edited by Jean Barilla, M.S., Keats Publishing, Inc., 1995