Regulation of the metabolism of linoleic acid to arachidonic acid in rat hepatocytes

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Abstract
When 5×106 hepatocytes were incubated for 40 min with from 0.15 to 0.60 mM [1‐14C]linoleic acid, [1‐14C]6,9,12‐octadecatrienoic acid, or [1‐14C]8,11,14‐eicosatrienoic acid, there was a concentration‐dependent acylation of radioactive metabolites into both triglycerides and phospholipids. When the concentration of either [1‐14C]linoleic acid or [1‐14C]8,11,14‐eicosatrienoic acid exceeded 0.3 mM, there was no further increase in the metabolism of either fatty acid to other (n−6) metabolites. When the concentration of [1‐14C]6,9,12‐octadecatrienoic acid exceeded 0.15 mM, there was an apparent substrate‐induced inhibition in its metabolism to 8,11,14‐eicosatrienoic acid. With all three substrates (0.3 mM), there was time‐dependent metabolism to other (n−6) acids. Cells then were incubated simultaneously with 0.3 mM [1‐14C]linoleic acid along with 0.15 to 0.45 mM 6,9,12‐octadecatrienoic acid or 8,11,14‐eicosatrienoic acid. These exogenous nonradioactive (n−6) acids suppressed but did not abolish the conversion of [1‐14C]linoleate to radioactive arachidonate. These findings suggest that some linoleate is converted to arachidonate without intracellular mixing of 6,8,12‐octadecatrienoic or 8,11,14‐eicosatrienoic acids. This hypothesis is supported by the finding that exogenous linoleate did not markedly affect the metabolism of [1‐14C]6,9,12‐octadecatrienoic or [1‐14C]8,11,14‐eicosatrienoic acid by microsomal chain elongating or desaturating enzymes.

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