cis-Unsaturated fatty acids inhibit cap formation on lymphocytes by depleting cellular ATP.

The inhibition of anti-immunoglobulin cap formation on lymphocytes by cis-unsaturated fatty acids, but not saturated or trans-unsaturated fatty acids, which recently been reported (Klausner, R. N., Bhalla, D. K., Dragsten, P., Hoover, R. L., and Karnovsky, M. J. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 437-441), can be accounted for quantitatively by the effects of the fatty acids on ATP levels in the intact cells. Only the cis-unsaturated fatty acids lowered the cellular ATP level sufficiently (to < 80%) to inhibit cap formation significantly. The profile for the dependence of cap formation on cellular ATP level obtained with the fatty acids is very similar to the corresponding profile described previously for several capping ligands and a range of metabolic inhibitors used to depress the cellular ATP levels. Oxygen electrode experiments indicate that the unsaturated, but not the saturated, fatty acids can uncouple lymphocyte mitochondria in intact cells, whereas both types of fatty acids can uncouple isolated rat liver mitochondria. The difference in the effect of the two types of fatty acids on ATP levels in the intact cells is attributed to the inability of the saturated fatty acids to penetrate in sufficient concentrations to the mitochondria to cause uncoupling. The protective action of external calcium against inhibition of capping by the free fatty acids is attributed to the effect of calcium in cross-bridging the anionic fatty acids and reducing their effective concentration. These interpretations account for all of the experimental data and are much simpler than the model proposed by Klausner et al.