Two different pathways, one theoretical and the other experimental, have led us to consider lipids as possibly the most important constituents involved in the dualistic patterns of physiopathological manifestations. The study of all the constituents of the organism—electrolytes, proteins, carbohydrates and lipids—has shown that for each of them, a rough division into two classes with antagonistic reactivity can be made according to the positive or negative electrostatic character of their polar groups—nucleo philic or electrophilic for some, anionic or cationic for others. However, these fundamental differences which can explain their intervention in processes in which dualism is apparent, do not represent the reason for their role in the induction of patterns.

The reactions in which some of these constituents take part are carried out as rapid changes while others are completed only slowly. It is these slow reactions, once accomplished, which tend to be stable for long periods of time. Since such stability is characteristic of clinical and analytical manifestations which have dual patterns, it appeared logical to consider the constituents with slow reactivity which are related to these manifestations. Because of their hydrosolubility, and the rapidity of the reactions in which they take part, most electrolytes, proteins and even carbohydrates probably play a lesser role in these long lasting processes.

The lipids, on the contrary, seem to be especially suited for this role. Many of the reactions in which the lipids participate are slow. As we will see later, this is primarily because of their insolubility in water. They form in the organism a group "apart" from all the water soluble constituents, a fact which permits them to function through proper reactions largely without continuous interference from the other constituents. For these reasons, the lipids appeared to be the most likely of all constituents to be of major importance in physiopathological manifestations with long lasting patterns. The study of the lipids has substantiated this.

However, before discussing these substances and their properties, a nosological problem must be considered: What are lipids? How can they be defined?

Definition Of Lipids

The literature fails to furnish an adequate definition for the group of substances that show those properties which biochemistry and experimental biology attribute to the lipids. A definition on a chemical basis, such as one which considers lipids to be fatty acids and fatty acid derivatives, appears to be insufficient. It excludes substances such as those forming insaponi fiable fractions which not only have properties attributed to lipids, but continuously intervene in the processes related to them.

Physical characteristics such as "greasiness" and solubility come nearer to the real situation without providing a satisfactory definition. Bloor's definition (Note I), widely accepted today in spite of having been found inadequate, has introduced—in addition to the important solubility characteristics—certain less acceptable criteria such as the origin of these substances and the direct relationship to fatty acids. Without these criteria, lipids would have to include the group of hydrocarbons which have the same solubility property but usually are not encountered in organisms. However, with these criteria, Bloor's definition, besides limiting the field too much through the requirement for a relationship to fatty acids, excludes the entire important group of synthetic agents with similar properties. To be complete, a definition would have to include these artificial substances.

Thus confronted by the need for a satisfactory general definition, we proposed one in 1940 (23) which has since been of great help to us in all our research: a lipoid is a polar nonpolar substance in which the non polar part is predominant. It is thus formed by one or more polar groups bound to one or more nonpolar groups, the last being energetically predominant. In terms of intervening forces, this definition considers the cohesion forces of the nonpolar part, and especially those related to its surface and known as the constant "b" of van der Waals forces, which in lipoids are predominant upon the electrostatic forces of the polar part. The definition has provided the key for the study of the multiple problems in which these substances appear to be involved. This definition appears acceptable since it explains all the known properties of the lipids. Furthermore, the study of the specific relationship between the forces involved could even predict new properties, as will be shown later.

The distinction between natural and synthetic substances as a basis for a definition has been obsolete in biochemistry for a long time. In our study however, it appeared to be didactically useful to indicate whether or not a substance is encountered naturally in the organism. Therefore, while adhering to our general definition, we have employed the term "lipoids" for the entire group of polar nonpolar substances with a predominance of the nonpolar part, and have conserved the term "lipids" to designate the naturally occurring members. With this separation, we have also avoided a certain apprehension felt by many workers about incorporating indis tinctly, in the same group of agents, substances with vastly different chemical constitutions, which until now have not been associated with lipids. The fact that, beyond physicochemical constitution, biological properties characterizing the lipids are common to the entire group of lipoids, will in time, we hope, help to reduce the importance of this separation between lipoids and lipids.

Schematic representation of the predominant relationship of the polar and nonpolar parts in hydroids

Fig. 61 bis. Schematic representation of the predominant relationship of the polar and nonpolar parts in hydroids, borderline substances and lipoids.

The structure of the lipoids—with a large variety of polar and nonpolar groups but always with the same characteristic energetic relationship between them—has led to a logical systematization of these substances, using the nature of the polar and nonpolar groups as criteria.