Compartmental analysis of linoleate and palmitate turnover in a murine carcinoma

We have carried out a balance study in Ehrlich ascites carcinoma in mice to determine whether large amounts of free fatty acids (FFA) could be diverted to an oxidative fate as suggested by earlier workers. At least 90% of the FFA tha turn over in the Ehrlich ascites tumor fluid are incorporated into the cell lipid esters of this carcinoma. Simultaneous with our balance study, we have compared the metabolic fate of essential and nonessential fatty acids (FA) in vivo in mouse Ehrlich ascites tumors using [1-14C]linoleic acid and [9,10-3H]palmitic acid complexed to mouse serum albumin. We followed the early disappearance of labeled FFA from the tumor system and the appearance of radioactivity in various tumor lipids and calculated rates of esterification and recycling of FA esters to FFA by cancer cells in vivo using multicompartmental analysis. We also estimated rates of "irreversible" disposal of FFA (combined rates of oxidation and transfer to host) in this tumor system. All rates for essential FA were found to be very similar to those for nonessential FA; however, some subtle differences seemed to exist; e.g., linoleate tended to disappear from the extracellular FFA pool faster than did palmitate and to appear in cellular phospholipids more rapidly than did palmitate, but the differences were not statistically significant. The major metabolic pathway for both classes of FFA was participation in an extremely rapid "futile cycle" of FA esterification (primarily into phospholipids) and hydrolysis. This cycle operates approximately 40 to 60 times faster than the rate of net FA esterification required for tumor growth (400 to 600 versus 10 nmol FA per min per 7-ml tumor). The "irreversible" disposal of FFA, based upon tracer studies with both essential and nonessential FFA, was approximately 6 times faster than the rate of FFA utilization for net growth.