Mainly on account of the fact that a co-enzyme function has been established for a number of vitamins, many investigators are inclined to generalize and therefore to direct their researches towards the discovery of enzymatic reactions in which the respective ergons act as co-enzymes. Following on results obtained in a study of plant growth regulators, however, we came to consider a physico-chemical type of action to be more probable for these ergons than an enzymatic, more chemically reactive one. This action would then consist in influencing the properties of physiologically important interfaces, in this case the protoplasmic membrane. Of the observations leading to this view the more important are discussed and demonstrated, including the growth substance activity established for certain normal fatty acids. After extending this review to other physiologically active compounds, just as the growth substances of a predominantly lipophilic (nonpolar) structure, and mostly containing hydrophylic (polar) substituents in particular positions (as e.g., the fat-soluble vitamins, notably vitamin D, steriod-hormones, cardiac glucosides and, to a certain extent, carcinogenic hydrocarbons), the question is asked whether there is any reason why the concept of ergon action should be limited to the co-enzyme type and not broadened to include different modes of action, according to the predominance of either hydrophilic or lipophilic character in the active compound. This question is answered on the side of broadening the concept after analysis of the above-mentioned material, which among other things points to the much smaller structural specificity of the lipophilic ergons (generally rather chemically inert) as compared with that of the hydrophilic group (of more chemically reactive compounds). Moreover, the differentiation of structure within the first group is on the whole very much smaller, and with this is probably connected overlapping of each others actions. For a certain type of action in this group (e.g., oestrogenic activity) the location of the hydrophilic substituents in the variable lipophilic skeleton, however, is extremely important. With the steroid hormones it appears that besides a completely flat structure (trans-trans-trans linkage of the ring systems), a fact already known, the spatial position of the substituents determines the intensity of the action. This is optimal if hydrophylic and lipophilic substituents are situated on opposite sides of the central plane, resulting in a triplex layer structure of the molecule. For the growth substances comparable requirements were deduced earlier in a different way, and now they have been established also for steroids with odoriferous properties. These facts form an additional argument for the view that these types of non-polar—polar ergons function in boundary systems. The action of these compounds, predominantly physico-chemical in our opinion, generally seems to be more dependent on the structure of the receptor (“substrate”) than that of compounds specifically soluble in water, which on the whole represent the chemical reactive type and comprise all ergons for which a co-enzyme function has been proved. The degree of interaction ergon/receptors which finally determines the intensity of the action, appears to be extremely dependent on the number of bonds (in the lipophilic category chiefly weak forces like London- Van Der Waals' attractions and hydrogen-bonds), which depends in turn on the “fitting” of ergon and receptor. From these points of view the great influence of location and spatial position of the substituents then becomes intelligible.
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Jul 1, 1960
W E Schlaretzki 
