Biosynthesis of fatty acids and cholesterol considered as chemical processes

T h e expansion of knowledge concerning biosynthesis of lipids has become almost explosive ; and any review of its present state is likely to be overlaid by new developments by the time it is printed. Enough is already known, however, to show that lipids, in comparison with proteins and carbohydrates, are built up by an unusually wide vAriety of enzymic reactions representing many different chemical types. This article attempts a survey, from the viewpoint of an organic chemist, of the processes leading to biosynthesis of fatty acids and of cholesterol. It might be objected that enzymic transformation of a substrate can rarely be matched-for speed and adaptability to a cool substantially neutral aqueous medium-by the same transformation executed in vitro without enzymes; and therefore that procedures which are possible or impossible in a chemical laboratory have no necessary relation to the capabilities of a living cell. Yet few enzymic reactions are known which have no counterpart in organic chemistry: considered as chemical transformations of substrate into product, most are of quite familiar type. If enzymes, like other components of living matter, have undergone evolution and adaptation, they could be expected to mediate processes which are not too difficult to effect without specific catalysis. The apo-enzyme would have undergone progressive development of its power specifically to adsorb reactants and to facilitate the charge-transfers, in substrate and coenzyme, necessary for reaction. The entropy and energy of activation are thereby progressively lowered ; but if they were initially too high, evolution could not have progressed. The function of an enzyme being so to provide an ideally favorable environment for an inherently facile chemical change, the ordinary laws of chemical reactivity can be used to discuss and predict the course of biosynthesis. The justification of this approach is found in its many successful predictions and in its power to limit the number of hypotheses to be tested by experiment; its dangers lie in the temptation to accept a chemically plausible mechanism without critical testing, and in the tendency to regard as a single chemical step an enzymic process which may prove to contain several.