The Fats of Life: Essential Fatty Acids in Health and Disease

5. Oxidation and Lipid Peroxidation

60 Oxygen is essential for survival. Without sufficient oxygen, as a result of suffocation or because the heart stops pumping oxygenated blood through our arteries, we can die within minutes. When life in the form of simple unicellular organisms evolved, there was virtually no oxygen in the earth’s atmosphere. It was not until photosynthetic organisms such as cyanobacteria evolved that oxygen began to accumulate in the atmosphere and in the oceans. However, because of its chemical reactivity, it was rapidly consumed in the early environment . Substances with which it reacted were ultimately used up (oxidized), and oxygen began to accumulate. It eventually made up about 20 percent of the atmosphere, where it has remained for hundreds of millions of years (Kump, Kasting, and Crane 1999, 182). Oxygen’s Toxic Properties Primitive biological organisms floating around in the early seas, when oxygen levels were low, needed to develop ways to protect themselves from oxygen and its highly damaging free radicals. Those that did not evolve with protections succumbed to the ravages of oxygen in their environment and died out. Most organisms evolved with elaborate systems, programmed in their genetic makeup, to ward off the detrimental reactions of oxygen. Eventually some organisms evolved with systems to utilize oxygen for their own benefit; these are known as aerobic organisms. They tend to be much more complex than anaerobic organisms, including their ways for handling oxygen to avoid being destroyed by this life-sustaining gas. Substances that readily react with oxygen are generally known as reduced substances, whereas those formed after they react with oxygen are oxidized substances . The process of reacting with oxygen is known as oxidation. Chemists have several ways of defining oxidation, but it will suffice to say that substances 5 Oxidation and Lipid Peroxidation 60 OXIDATION AND LIPID PEROXIDATION 61 that are produced after reactions with oxygen are oxidized, whether they react directly with oxygen or indirectly through intermediary molecules. Oxygen may go through several stages in the process of reacting with other substances, depending on what substance it reacts with and the environment where the reaction takes place. The stages that oxygen goes through between molecular oxygen in the air and the combined form in water, as a result of a series of single-electron reductions (+e–), are represented as follows: +e–/H+ +e–/H+ +e– +e–/H+ O2 O2 –/HO2 H2O2 OH• H2O / H3O+ / OH— where O2 is molecular oxygen; O2 – is known as superoxide anion (a free radical); HO2 is the perhydroxyl radical (an acidic form of superoxide); H2O2 is hydrogen peroxide, a highly reactive substance but not a free radical; OH (often written as OH•) is the hydroxyl radical, one of the most reactive substances known, which never exists for more than a fleeting instant in the environment because of its propensity to react with almost anything it encounters; and H2O is water, which also exists in its acidic (H3O+) and alkaline (OH–) forms. It is possible for hydrogen peroxide to form its alkaline anion (HO2 –), although this is important only under strong alkaline conditions. Another form of molecular oxygen, known as singlet oxygen (1O2), is much more reactive toward organic and biological molecules than the common form of oxygen in the atmosphere, which is technically known as triplet oxygen (3O2). Singlet oxygen may be generated in biological systems under certain conditions and may be involved in many of the damaging reactions discussed below. The free radicals and other reactive forms of oxygen listed here are collectively known as reactive oxygen species. Ozone and some highly reactive organic substances (such as lipid peroxides discussed below) are also lumped into this category of reactive oxygen species. Although they may occasionally play a beneficial biochemical or physiological role, they are more often associated with adverse health conditions. Their detrimental chemical characteristics are frequently involved in toxic effects. Managing Our Oxygen When we breathe air into our lungs, oxygen crosses membranes of cells lining the alveoli of the lungs, enters the blood, and crosses membranes of red blood cells in the capillaries of the lungs. Red blood cells contain hemoglobin, a protein whose primary function is to escort oxygen to tissues where it is needed and prevent unwanted reactions. Hemoglobin is uniquely designed to pick up oxygen molecules in the lungs, where oxygen is abundant, and release it in NUTRITIONAL, CHEMICAL, AND PHYSIOLOGICAL PROPERTIES 62 tissues that are actively working. Muscle...