Uptake of Free Fatty Acids by Ehrlich Ascites Tumor Cells.

Plasma free fatty acid is the form in which fat is transported from the adipose tissue for utilization (2). Almost all of the FFAI present in plasma is tightly bound in a noncovalent complex with albumin, and less than 0.01 y0 is present unbound (i.e. in free solution) under ordinary conditions (3). However, in spite of the high association constants for binding of FFA to albumin, FFA leave the plasma compartment at a rate more t,han 10,000 times the rate at which albumin leaves (2, 4). The present studies were initiated in an attempt to elucidate the mechanisms by which FFh are transferred from albumin to the cell. For these initial studies, a homogeneous cell suspension was selected to permit investigation of FFA-cell interactions directly, without the need to consider, in addition, factors affecting the transfer of FFA from the vascular space (or incubation medium) through the extracellular space to the cell surface. Goodman has previously studied the binding of FFA to erythrocytes (5), but, it was felt that results of greater general interest might be obtained by the use of acceptor cells that have a metabolic pattern more like that of the usual mammalian cell and that, in particular, oxidize and esterify long chain fatty acids at a significant rate. Because of their ready availability and reasonable homogeneity, Ehrlich ascites tumor cells were chosen for this investigation, with the realization that, at least from a quantitative point of view, the results might not be the same in nontumor cells. In an attempt to distinguish between effects on FFA uptake per se, and effects on subsequent metabolism, we have employed a fatty acid analogue, 3,3,12,12-tetramethylmyristic acid. Fatty acids substituted at or near the carboxyl and w ends have been shown previously to resist oxidation, although they can be absorbed, transferred through the plasma compartment and esterified, but at a lower rate than normally occurring long chain fatty acids (6-8). Where applicable, results with the fatty acid analogue have been compared with those obtained with palmitate under identical conditions.