The analysis of the changes induced by lipids has emphasized certain characters which appear of capital importance for the understanding of the biological intervention of these substances. In one kind of activity a lipid acts through its lipoidic properties. From the data concerning its distribution in the organism it can be seen that, due to its solubility characters, a lipid introduced in an organism will be selectively retained by the existing lipidic system. When such intervention through its lipoidic properties takes place, the nonspecific character of the activity of the lipid is prevalent. A second kind of activity results from the bond realized through the charge of the polar groups. The positive or negative character of these polar groups determines thus the nature of this second kind of activity. A third kind of activity results from the chemical constitution of the polar group, which will induce selective combinations and consequently will have a more specific influence. A fourth group of changes are induced by the activity which takes place at the nonpolar group of the lipid and more specifically at the energetic formations present in it. They will have a still higher character of specificity.

Table X

level

effects of sterols

effects of fatty acids

Cells

Prolongs youth character Increases potassium content Decreases sodium content Reduces membrane permeability Reduces cellular oxidation Reduces chloride content

Induces rapid aging Decreases potassium content Increases sodium content Increases membrane permeability Increases cellular oxidation Increases chloride content

Tissues

Lowers pH of lesions Lowers chloride content of lesions

Lowers water content of lesions

Raises pH of lesions Raises chloride content of lesions

Raises water content of lesions

Organs

Induces somnolence Induces diuresis Induces constipation Induces tachycardia

Induces insomnia Induces oliguria Induces diarrhea Induces bradycardia

Systemic Blood

Induces hyperthermia Induces hypertension

Increases RC volume Decreases RC sed. rate Increases persistence of oxygen fixation Determines persistence of

RC isolation Determines hyperleucocytosis Determines eosinophilia Decreases kalemia

Induces hypothermia Induces hypotension

Decreases RC volume Increases RC sed. rate Decreases persistence of oxygen fixation Determines formation of sludge

Determines leucopenia Determines eosinopenia Increases kalemia

Urine

Induces water excretion Induces sulfhydryl retention Induces calcium excretion Induces chloride excretion Induces sodium excretion Induces phosphate retention Induces retention of surface active substances

Induces water retention Induces sulfhydryl excretion Induces calcium retention Induces chloride retention Induces sodium retention Induces phosphate excretion Induces excretion of surface active substances

With this systematization of the activity of the lipids, a further systematic analysis of the influence exerted by the lipids appears possible.

Through its selective distribution, the administration of a substance having lipoidic properties will influence those entities which have lipids in an active form in their constitution. The influence exerted will thus be proportional to the richness of the entity in these active lipids. This fact explains why the administration of a lipid or lipoid affects selectively the abnormal entities rich in free lipids and to a much lesser degree, the normal ones. It is this selective distribution which will further limit the activity of the lipoid to the lipidic system and most manifestly to the abnormal entities. In the frame of this limitation, this activity results from the charge of the polar group. Similar effects are thus obtained for all the different lipoids which have the same electric positive or negative character of their polar group. This explains why one can use different agents from the same group and still obtain similar results. Agents chemically so different as fatty acids, mercaptans, persulfides, aldehydes or epichlorohydrine, have similar activity because they all have negative polar groups. The characteristic of the effects resulting from the electrical character of the polar groups, is that they are common for the groups having the same sign and diametrically opposite for the agents with a positive or a negative polar group.

This effect was clearly seen in fatty acids in which the negative car boxylic polar group was changed into the positive primary alcohol. The biological effects of the new substance were opposite.

It is in the third kind of activity that the chemical nature of the lipoids intervene. Certain effects resulting from the bond of an amino polar group will thus be different from that of the alcohols, although both act as positive energetic centers and as such have exerted other common effects. The same is true for the carboxyl and thiol groups.

Still more specific appear the effects resulting from the intervention of the energetic factors present in the nonpolar group, such as the double bonds, and the energetic formations they realize such as conjugated, or two double bonds separated by a methylenic carbon.

The various mechanisms involved have explained further the different kinds of biological effects which result. The action of the lipid by means of the lipoidic effect will thus influence general, nonspecific manifestations, such as those concerning the permeability of membranes. Only secondarily, will these changes in membrane permeability influence the different metabolic processes which the membrane governs.

In the second group of changes, related to the intervention of the polar groups, the antagonistic effects induced were seen to concern processes resulting from membrane permeability. It is only in a third change that a more specific action upon the different metabolic processes has to be considered. These are concerned with an intervention upon metabolites or the agents governing them. The character of this last lipidic intervention is its specific influence exerted upon a definite metabolic system.

We tried to interpret the influence exerted by a lipid or lipoid according to the above systematization. The recent development of the biochemical methods of investigation has put into limelight many biochemical processes by considering them as isolated metabolic entities. Most of them were seen to result from the intervention of enzymes upon more or less specific substrata. One of the principal objectives of the actual pharmacodynamic studies is to correlate as directly as possible, biological effects of different agents to specific metabolic processes, most of them corresponding to a change in an enzymatic process. This approach, while very interesting, would not take into consideration the important role played by the nonspecific activity of lipids and lipoids. These nonspecific influences through changes in the lipidic system induce different changes in different metabolic processes. A nonspecific change in membrane permeability will affect many enzymatic processes. It explains the existence of similar influences exerted upon these processes common to agents which have nothing more in common than their lipoidic properties and the presence of a positive or a negative character of their polar group. It is this character which binds an effect to the nonspecific intervention. This so systematized analysis has thus permitted to separate the biological activity of the lipids and lipoids, the more specific from the lesser influences, and correlate each one to a proper or common character of the agent. This view has amply simplified the study of the pharmacodynamic intervention of these substances.

Other Constituents

In addition to the chemical elements and lipids, other constituents have been studied from the dualistic point of view. Although the other constituents have received less emphasis, interesting information has been obtained.