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
Characteristic of the structure of this group of steroids is the presence of a hydroxyl at C3 and a long chain bond at C17. Through the hydroxyl, the center at C3 has a nucleophilic character. This is reinforced by the presence of a double bond between C5 and C6 which, by paralleling the bond between C3 and C4, increases its ionic character and consequently the reactivity of the hydroxyl bond to C3. Through this hydroxyl, sterols combine in general with substances having a negative polar group to form esters.
Besides the capacity to combine with fatty acids in general, one of the most important characteristics of the principal sterol of animals, cholesterol, is its selective affinity for certain fatty acid members, the polyunsaturated. We tried to explain the specificity of this bond through an interesting process which could be called "steric coupling."
In this process, two molecules, usually lipoids, are kept together not only by the combination of their polar groups but also through a bond between their nonpolar parts. The two molecules are reciprocally attracted through the multiple forces present in the nonpolar groups. Some are related to attached centers, while some, such as those corresponding to cohesion forces, are related to the rings themselves. An important factor is the rigidity of the sterol molecule which permits another molecule, if it is flexible, to make the steric coupling. The rigid skeleton not only keeps the energetic centers of one molecule in a fixed position but permits the flexible aliphatic chain to cover over the polycyclic molecule and thus bring the energetic centers of one molecule in contact with those of the other. Through this, steric coupling completes the bonding of the polar groups. The greater the concordance between energetic centers in both molecules, the more perfect the coupling is, for the more complete is the reciprocal neutralization of the energetic centers of the two molecules. Steric coupling explains why, of all the fatty acids present in the organism, cholesterol seems to prefer to bind those with polyunsaturated chains. It is these fatty acids which have several energetic centers in the nonpolar group as represented by double bonds. The long chains of these fatty acid molecules, having a certain degree of flexibility, will then complete the steric coupling. (Note 12)
Steric coupling, in addition to its general importance in biology, where it represents a kind of molecular reactivity, seems to explain the antagonistic influence exercised by different constituents, especially the sterols and polyunsaturated fatty acids. Through steric coupling, cholesterol could influence the activity of these fatty acids more directly related to the non polar group. It has to be emphasized, however, that the neutralization resulting from steric coupling is not irreversible. On the contrary, through the intervention of various factors, such as the breaking down of the bond between the polar groups, the two coupled molecules can regain their independence. This would explain the relative lability of the combinations between fatty acids and sterols. The antagonism between fatty acids and sterols is an important aspect of biological dualism which will be discussed in more detail later when these substances are studied in terms of their influence at the different levels of organization.