Acetylcholine (ACh) is hydrolysed very quickly and butyrylcholine (BuCh) very slowly by AChE while PsChE hydrolyses BuCh very rapidly, at about 23 times the rate of ACh5. Burgen and Macintosh6 suggested that the natural substrate for PsChE might be something other than ACh. This substrate may be BuCh since it seems to be hydrolysed by PsChE more rapidly than any other substrate7. The capacity for ACh synthesis is widely distributed in animal tissue but is predominant in nervous structures6 and liver tissue (serum PsChE is also formed in the liver8); it requires the presence of adenosine triphosphate, co-enzyme A (CoASH), acetate or citrate, choline and the enzymes acetyl kinase and choline acetylase6,9.In tissues, especially those of the liver, certain other acyl-coenzyme A derivatives are equally capable of taking the place of acetyl-coenzyme A (CH3.CO ~ SCoA) to give the corresponding choline esters9. Fig. 1. Pathway of fatty acid metabolism in mammalian liver () including postulated synthesis and breakdown of toxic choline esters ()In mammals, fatty acid metabolism occurs mainly in the liver. Since the penultimate product of fatty acid degeneration and the primary product of lipogenesis in the fatty acid cycle10 (Fig. 1, in thin lines) of fatty acids having even numbers of carbon atoms is butyryl-coenzyme A, we postulate that this, and to a lesser extent the acyl-coenzyme A derivatives of certain other higher fatty acids, become involved in the choline ester synthetic pathway. The products, particularly BuCh, have a powerful nicotinic action11 and if not quickly destroyed would probably exert undesirable and toxic effects. We consider that the principal biological function of PsChE might, therefore, be to hydrolyse this BuCh preferentially, almost at the site of its formation and allow the products of hydrolysis to return to their respective metabolic pathways (Fig. 1, in thick lines). Some support for this hypothesis is provided by the seasonal variation observed in the PsChE titre of horse serum, which reaches a maximum in late summer12 thereafter declining, to parallel closely the seasonal variation in fat metabolism.-Aminobutyrylcholine, isolated from pig brain extracts13, is a very poorly active cholinergic compound compared with ACh. It is not hydrolysed by AChE and is only poorly hydrolysed by PsChE. Its exact function is unknown but it is possible that it is a functionless byproduct of the choline ester synthetic pathway.