Besides their constructive role in establishing boundary formations, fatty acids appear to serve various other purposes in the organism. They can be used as caloric metabolites, and they play an active functional role in a biological change. While all fatty acids may exhibit these three activities—caloric, constructive and functional—there are important individual differences. With the carboxyl as common polar group, the differences between the various fatty acids can be related to the nonpolar groups. We will discuss this aspect of fatty acids, emphasizing only what can be considered to be new contributions to understanding the biological role of the substances.

Rancidity

The study of changes which take place in vitro, on lipids and especially on fatty acids after they have been separated from the organisms, led us to consider a possible parallelism between them and the changes which take place in the organism. We tried thus to utilize especially the knowledge furnished by the study of the chemical deterioration of natural fats generally known as rancidity (28), to better understand and also to systematize many of the processes occurring in vivo.

Three types of rancidity are described. In one—hydrolytic rancidity— fats are separated in free fatty acids and glycerol (or mono- or di glycer ides), through the intervention of lipolytic enzymes. These are often produced by molds (Penicillium, Aspergillus, etc.) or by microbes rich in such lipolytic enzymes or even the lipase present in the tissues from which the lipids are obtained. The characteristic of this type of rancidity is the intervention of enzymes and the appearance of free fatty acids as a result.

In a second type of rancidity, also occurring under the intervention of enzymes, an oxidative process is involved. The characteristic of this type of rancidity is that it affects almost, if not exclusively, saturated fatty acids, converting them into methyl ketones by a beta oxidation process. This "perfume rancidity" called so because of the odor of the methyl ketones with seven, nine or eleven carbons which result—takes place apparently through the intervention of a peroxidase present in certain molds (such as penicillium glaucum). One of its characteristics is that it occurs especially on saturated fatty acids with a low number of carbons (8 to 12).

The third type of rancidity groups together the oxidative changes which take place at the unsaturated nonpolar group of the lipids. As they result from the intervention of double bonds, the reactions differ according to the energetic center present. In one which occurs at room temperature only for the conjugated fatty acids, such as eleostearic acid, and at 100°C only to some extent for oleic, linoleic and linolenic acid, the oxidation leads to the appearance of peroxides. (29) In another form of this oxidation, taking place for oleic, linoleic and linolenic fatty acids at room temperature or below 50°C, hydroperoxides result, as it has been shown by Farmer and coworkers, first for rubber (30) and after for fats (31). Another important fact seen in rancidity changes is that the atmospheric oxidation of poly ethenoid fatty acids can result in a displacement of the double bonds with the appearance of conjugated isomers. (32)

The study of natural rancidity has represented the basic guide for our study and systematization of the processes encountered in normal and abnormal physiology. We searched and found this similarity not only in general outlines, but also for most of their details. By referring to the processes found in rancidity, we were able to identify, besides enzymatic lipol ysis and enzymatic Knoop beta oxidation, known to occur in the organism, also the intervention of hydroperoxides, peroxides and the conjugation of double bonds. Not only the processes themselves but also the conditions under which they take place and their inter relationship have been found to parallel in vivo those which can be seen in vitro.

We will see all along in the study of fatty acids how far the biological intervention of this parallelism goes.