ABSTRACT
It is generally accepted that linoleic acid is metabolized to arachidonic acid in the endoplasmic reticulum as follows: 9,12-18:2 → 6,9,12-18:3 → 8,11,14-20:3 → 5,8,11,14-20:4. This pathway requires the participation of position-specific acyl-CoAdependent 6-and 5-desaturases with an intervening alonyl-CoA-dependent chainelongation step. When the pathways of unsaturated fatty acid biosynthesis were being elucidated, Stoffel and Ach (1) presented evidence that linoleate was chain-elongated to 11,14-20:2, which was then desaturated at position 8 to yield 8,11,14-20:3. We synthesized [1-14C]1 1,14-20:2 and [l-14C]11,14,17-20:3. When they were incubated with rat liver microsomes, they were desaturated at position 5 to yield 5,11,14-20:3, and 5,ll,l4,l7-20:4, respectively. At that time, we concluded that rat liver microsomes did not contain an 8-desaturase, and that 6,9,12-18:3 was an obligatory intermediate in the biosynthesis of arachidonate (2). Our results were corroborated by Dhopeshwarkar and Subramanian (3,4) who showed that brain also lacked an 8-desaturase. At about the same time, Albert et al. (5) incubated [1-14C]11-14-20:2 with testes microsomes and isolated the radioactive trienoic acids. When they degraded them, they found radioactive 5-and 8-carbon aldehydo methyl esters, suggesting that rat testes contained an 8-desaturase. More recently, Cook et al. (6) reported that cultured C6 glioma cells metabolized deuterium-labeled fatty acids via a number of pathways, one of which could proceed via desaturation at position 8.
