EVIDENCE FOR THE INVOLVEMENT OF CARNITINE-DEPENDENT LONG-CHAIN ACYLTRANSFERASES IN NEURONAL TRIGLYCERIDE AND PHOSPHOLIPID FATTY-ACID TURNOVER

This study focuses on the potential involvement of carnitine palmitoyl transferase (CPT) on the phospholipid and triglyceride fatty acid turn over in neurons. This category of enzymes, which has been identified i n several rat brain tissues, is well known for its role in modulating cellular fatty acid oxidation. Neuronal cell cultures from rat brain c ortex incorporated radioactive palmitate or oleate into phospholipids and triglycerides. The largest fraction of radioactive fatty acids was recovered in phosphatidylcholine followed by triglycerides and, to a lesser extent, phosphatidylethanolamine. CPT activity measured in neur onal lysates obtained from neurons treated with 40 muM 2-tetradecylgly cidic acid (TDGA) was almost completely abolished. Furthermore, betwee n 2 and 10 muM TDGA CPT activity dropped more rapidly than between 10 and 40 muM. When the cells were pretreated with TDGA, the incorporatio n process of either radioactive fatty acid into triglycerides was dose -dependently suppressed. Radioactive fatty acid incorporation into pho sphatidylcholine was significantly decreased in cells treated with TDG A. In contrast, phosphatidylethanolamine reacylation was essentially n ot affected by the CPT inhibitor. Similar results on the fatty acid in corporation into triglycerides and phospholipids were observed with ne urons treated with palmitoyl-DL-aminocarnitine (PAC), a reversible CPT inhibitor, which does not consume free CoA. These effects do not seem to be the result of an inhibitory activity toward one of the steps in volved in the acylation-deacylation process of triglycerides or phosph olipids, as cellular lysates from TDGA-treated cells or lysates contai ning PAC incorporated radioactive fatty acids at rates comparable to c ontrols. Our results suggest that CPT may be an important partner in t he pathway of phospholipid and triglyceride fatty acid turnover in neu rons.