Studies on the cellular mechanism of free fatty acid uptake using an analog, hexadecanol

Hexadecanol was employed as a fatty acid analog in an attempt to elucidate the role of the carboxyl group in free fatty acid uptake. Large quantities of albumin-bound [1-(14)C]hexadecanol were taken up by Ehrlich ascites cells during in vitro incubation. More than 90% of the (14)C that was taken up remained as hexadecanol even after 1 hr of incubation at 37 degrees C. Addition of unlabeled hexadecanol did not appreciably alter the rate of [U-(14)C]glucose oxidation or incorporation into total lipids, suggesting that the slow rate of hexadecanol metabolism was not due to a toxic effect of this analog. However, more of the labeled glucose was incorporated into phospholipids and less into glycerides, indicating that hexadecanol did exert some metabolic effect on the cells. Uptake was temperature dependent but relatively unresponsive to the presence of glucose or fluoride and cyanide. Hexadecanol was incorporated into exchangeable and nonexchangeable cellular pools as determined by its availability for release to a medium containing albumin. These results indicate that a mammalian cell can rapidly take up large amounts of a long-chain hydrocarbon derivative that does not contain a carboxyl group. Furthermore, the data are compatible with the hypothesis that free fatty acids are taken up by a nonenzymatic process such as diffusion into the lipid phase of the cell membrane.