The constitution of arachidonic acid (preliminary communication)

Abstract

ARACHIDONIc acid is widely distributed in the animal body and its presence has been shown to be essential for the maintenance of the normal health of the rat. In rats which have suffered for many months from the fat deficiency disease first described by Burr & Burr [1930] the liver was found to be entirely free from this acid and only very small amounts were detected in other parts of the body. It was, however, retained if linoleic or arachidonic acid itself was included in the diet of the rats. The conclusion was drawn by Nunn & Smedley-MacLean [1938] that the rat can probably synthesize arachidonic acid using linoleic acid as its starting material. At this time all that was known as to the structure of arachidonic acid was that it contained a normal chain of 20 carbon atoms since it yielded arachidic acid on reduction [Bosworth & Sissons, 1934], that four double bonds were present and that, from the normal iodine value, these were unconjugated. We were therefore anxious to determine the position of the double bonds in the chain and to compare the structure of this acid with those of linoleic acid.Shinowara & Brown [1940] have, however, recentlypublished some preliminary results on the structure of this acid and suggested a formula though they emphasize that it is only tentative. The determination of the diene number of methyl arachidonate is interpreted by these authors as indicating the presence of about 5 % of conjugated bonds derived either from the presence of a small proportion of an isQmeric ester or from a rearrangement of the ester under the conditions of the diene determination. However, in the bulk of the acid examined, the bonds were not conjugated. The methods of oxidation used by these authors were ozonolysis and oxidation with permanganate in acetone solution. We, on the other hand, have used the action of an %queous alkaline permanganate solution and have arrived at entirely different conclusions from those drawn by Shinowara & Brown. We should have preferred to repeat and extend our experiments before publishing our results but in view of the communication of these authois and of the postponement of our experiments necessitated by present conditions, we have decided to publish them.Shinowara & Brown, with their methods of oxidation, did not detect any aldehyde higher than acetaldehyde, nor did they detect oxalic acid but they obtained indications of adipic and succinic acids and concluded that a double bond existed between the 18th and 19th carbon atoms and that the group : C. CH2 . C: characteristic of linoleic and linolenic acids was not present in the molecule.'We on the other hand deduce from our findings that the terminal chains of ten carbon atoms are similar in structure in both arachidonic and linoleic acids and that certainly three and almost certainly four of the groups CH. CH2. CH: occur in the arachidonic molecule.

The structure of arachidonic and linoleic acids

“…The results of ozonolysis and of acetoneKMnO4 oxidation of methyl arachidonate are in agreement with the constitution (II) A5 8 11"14-eicosatetrenoic acid, for arachidonic acid, which was proposed by Dolby et al [1940].…”

Fatty acids and feminism: Ida Smedley MacLean, the first woman to Chair the Biochemical Society

“…She identified linoleic and linolenic acids as the essential dietary fatty acids, and showed that these could be converted in vivo into the more complex 20 C polyunsaturated fatty acid, arachidonic acid, the precursor of the prostaglandins [10][11][12] . Finally, in 1940, just when the Lister was being evacuated from London to Cambridge to avoid bombing, she published the correct full structure for arachidonic acid including the positions of the double bonds 13 . This work was recently celebrated in a review in the Journal of Lipid Research 14 which highlighted the small quantities of material that Ida and her collaborators had to work with and the use of entirely traditional techniques, with no modern spectroscopy.…”

The discovery and early structural studies of arachidonic acid

“…These products suggested that the first double bond was at carbon-5 (hence the dicarboxylic acid, glutaric acid) and formation of the small amount of hexanoic acid located the terminal double bond at carbons 14-15. She thus characterized arachidonate as 5,8,11,14-eicosatetraenoic acid, a structure consistent with a biochemical origin involving linoleic acid (21).…”

“…Smedley-Maclean read this paper and was concerned that publication of her studies of the oxidative degradation of arachidonic acid, which yielded different conclusions, could not be postponed because of the conditions in London at that time (21). Rather than ozonolysis, she used oxidation by alkaline potassium permanganate to cleave the double bonds and form carboxylic acids (Fig.…”