This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
Although all the fatty acids are ultimately used by different organisms as caloric metabolites, the saturated and monoethenic members are most important from this point of view. Among the saturated and monoethenic fatty acids, the members with long chains appear to be those which are kept in reserve for caloric purposes. We could show that the principal form of caloric desmolysis, the Knoop beta oxidation, takes place directly, almost exclusively, on members with relatively short chains, that is, with a maximum of 10 or 12 carbons.
While fatty acids with short chains take part directly in these caloric metabolic changes, those with longer carbon chains must undergo preliminary changes before entering into caloric metabolism. A desaturation, changing a saturated fatty acid into a monoethenic, appears to be a first step in caloric metabolism of the long chain members. The monoethenoids thus can be seen to be intermediary forms between the saturated reserve and the short chain, easily metabolized fatty acids.
The double bond in these monoethenic acids would thus appear to have two uses: one, to reduce the melting point below body temperature and thus permit easy mobilization, and two, to induce changes which lead to the breaking up of the long molecule into two shorter ones which can be metabolized through the Knoop oxidation.
All the data indicate that this fission would not take place at the double bond but through a more complex process. A first change consists of oxygen fixation at the carbon near the double bond. This leads to the appearance of a hydroperoxide group. It is only in a subsequent step that the molecule breaks at a place between this carbon near the double bond and the double bond itself, resulting in the appearance of short chains which have an even number of carbons capable of being directly metabolized through the beta oxidation. (Note 4)
The position of the double bond in the naturally occurring monoethenic fatty acids, separating almost always a group of nine carbons toward the carboxyl or the methyl end, (Note 5) acquires a special significance for the breaking down of the molecules for caloric purposes.
The desaturation of the saturated fatty acids, which would represent a first step toward allowing them to participate in metabolic caloric changes, would usually take place in the liver, apparently through the same processes by which polyunsaturated fatty acids are partially saturated. (Note 6)
An interesting part of the caloric metabolism of the saturated and monoethenic fatty acids, which will be shown below, is their combination with glycerol to form triglycerides.
Although saturated and monoethenoid fatty acids enter into the formation of boundary membranes, the di-, tri- and tetraenic members seem to have a particularly important role in the constructive function of fatty acids. Some of them enter directly into the formation of the membrane; some form complex lipoids such as lecithine with the glycerophosphoric radical and nitrogen containing bases. As a rule, these last represent a lipoidic substrate which would act as a neutral natural solvent present in membranes, and as such, intervene in the realization of a diphasic medium at the level of the boundary formation. This medium would largely insure the orientation of the fatty acids at the separation surface and the formation of permeable lipidic layers.
The third role of fatty acids is as functional agents taking part in certain reactions. This activity appears to be strongly related to two factors: the presence of an uncombined carboxyl group and the energetic intervention of the double bonds of the nonpolar part of the polyunsaturated members.
Free fatty acids appear to be functionally active while the combined ones usually are inactive. The activity is related only partially to the direct capacity of the carboxyl to realize new combinations. It results from the induction exerted by the carboxyl upon the nonpolar group. The so called free fatty acids of the organism are probably bound in a labile form to proteins, but this bond will not influence the induction effect exerted upon the nonpolar group. The intensive positive carbon of the carboxyl, together with the zig zag disposition of the fatty acid molecule, causes the inductive effect to charge the successive carbons of the chain. They will thus show alternative signs. The even carbons show a negative character, while the odd ones are positive. The fact that oxygen combines with positive carbons explains not only why, as in Knoop oxidation, this bond occurs at C3, which is strongly positive, but also explains the so called alternate oxidation (33) where the other following odd carbons are binding oxygens. Through the influence exerted by the carboxyl, the double bond shows a special activity which has been worth studying.