There has been some tendency to regard the double bond as a weak, easily broken point of the molecule. Actually, it emerges as an important center of activity. With its capacity to become a semipolar center, and consequently, to bind or lose radicals, the double bond is an energetic center in the molecule. Its important characteristic is the ability to effect such changes without altering the chain of the molecule itself. Since this type of reaction is reversible and can be repeated for the same molecule, the double bond appears to represent a functional entity. Because the reaction principally involves nonmetallic elements, the unsaturated fatty acid takes an active part in the metabolism in which these elements appear.

The study of rancidity has helped us, by analogy, to systematize oxidation processes as they take place in vivo. In addition to Knoop beta, several other types of oxidation could be recognized in which double bonds intervene more directly. The double bond, with its semipolar character, influences nearby carbons, rendering them highly reactive. In one form of oxidation, a molecular oxygen is bound to a nearby carbon to produce a hydroperoxide formation, as was shown to occur in vitro by Farmer. (31) When, under certain circumstances, this oxygen fixation becomes reversible, the fatty acid will liberate the oxygen. It appears highly probable that in such a process, the oxygen is liberated as a free radical, the entire process thus corresponding to an activation of oxygen. The change of a molecular oxygen into a free radical would represent the physiological role of unsaturated fatty acids in oxidation processes.

The presence of two double bonds in non parallel position, common to most of the naturally occurring polyunsaturated fatty acids, is even more important; the two double bonds exert a particularly strong influence on the special carbon which is in the intermediary position between them. Because of the alternate induction produced by the strongly positive carbon of the carboxyl, the carbons of the chain have alternate characters, positive and negative. When an intermediary carbon also has a strong positive character, it appears to be especially able to fix oxygen. This strongly positive intermediary carbon, occurring in natural polyunsaturated fatty acids with more than two double bonds, may be the reason for the important role played by these acids when they act as essential fatty acids in the organism. (Note 7)

The study of rancidity has further shown that, while the in vitro oxidation of an unsaturated fatty acid under mild conditions such as room temperature leads to the appearance of hydroperoxides, oxidation at a higher temperature will result in another fixation of oxygen, this time at the double bond itself. Epoxides or peroxides will appear according to the ionic or molecular character of the oxygen. This extremely important process also occurs in rancidity under the influence of an enzyme. It is highly probable that a similar process takes place in vivo in those pathological conditions in which peroxides appear in the urine. Radiation, certain inflammations (especially those due to streptococci), administration of selenium preparations or of highly polyunsaturated fatty acids are followed by the appearance of these oxidizing substances in urine. As mentioned above, when these substances appear, there also are increases in indoxyl and glucuronic acid, which can be considered, up to a certain point, to result from abnormally intensive oxidation taking place on tryptophane and glucose. (See below.) While activation of oxygen is a physiological process, peroxides appear under abnormal conditions.