Metabolism and distribution of intramolecular excimer-forming dipyrenebutanoyl glycerophospholipids in human fibroblasts. Marked resistance to metabolic degradation.

Metabolism and intracellular distribution of fluorescent 1, 2-dipyrenebutanoyl derivatives of phosphatidylcholine, -ethanolamine, and -serine and phosphatidic acid (diPyr4PC, -PE, -PS, and -PA, respectively) in human skin fibroblasts (HF) has been studied. When HF cells were co-incubated with phospholipid vesicles containing diPyr4PC at 8 degrees C, considerable amounts of fluorescent lipid were incorporated into the cells. This incorporation occurred mainly by spontaneous diffusion, since 10-fold less of the vesicle marker, [3H]cholesteryl oleate associated with the cells. Also diPyr4PE, -PS, and -PA were incorporated efficiently into the cells, probably by the same mechanism. HPLC analysis of the cells labeled with diPyr4PA at 8 degrees C for 1 h showed that a considerable fraction of the lipid had been metabolized to the corresponding diglyceride and triglyceride. No metabolism of the other dipyrenyl lipids was observed at this temperature. When the cells were shifted to 37 degrees C, diPyr4PA was further metabolized to diPyr4PC, which represented 90% of total diPyr4 lipids after 8 h of incubation. DiPyr4PS was converted to diPyr4PE with an apparent half-time of 3 h, probably by decarboxylation in the mitochondria. In contrast to the PA and PS derivatives, no head-group modification of either diPyr4PC or diPyr4PE was observed even at this temperature. Stability of dipyrenyl lipids toward phospholipase A degradation was investigated by labeling the cells simultaneously with diPyr4PC and NBD6PC, a commonly used fluorescent glycerophospholipid derivative, followed by incubation at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)