Metabolism of 6,9,12-octadecatrienoic acid and 6,9,12,15-octadecatetraenoic acid by rat hepatocytes.

When 5.10(6) hepatocytes were incubated for 40 min with 0.015-0.3 mM (1-14C)-labeled 6,9,12-octadecatrienoic acid or (1-14C)-labeled 6,9,12,15-octadecatetraenoic acid there was a concentration-dependent acylation of radioactive metabolites into both phospholipids and triacylglycerol. However, when the concentration of either substrate exceeded 60-150 microM there was no further increase in the metabolism of either substrate to longer-chain (n-6) and (n-3) acids. When cells were then incubated for various periods of time with 60 microM substrate there was initial rapid removal of the substrate which was accompanied by its acylation into lipids. Over time, the amount of both substrates in lipids declined without an overall drop in specific activity. This decline was accompanied by an increase in long-chain (n-6) and (n-3) fatty acids. Similar results were obtained when the time-dependent metabolism of the two substrates was examined in individual hepatocyte phospholipids. Collectively, these findings suggest that when these two 18-carbon acids are produced by desaturation of dietary linoleate and linolenate that they are in part initially acylated into a labile phospholipid pool. Rapid release and subsequent further metabolism to longer-chain (n-6) and (n-3) acids may explain why these products of the 6-desaturase do not accumulate in membrane lipids.