METABOLISM OF POLYUNSATURATED FATTY-ACIDS IN NEURONAL CELLS DURING DIFFERENTIATION

Polyunsaturated fatty acids (PUFA) with 20 or more carbon atoms and 4 or more double bonds, the long chain PUFA (LCP), namely arachidonic (A A, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) are found in ver y high concentrations in specialized membranes of the central nervous system (CNS), such as the synapses and the retina, and accumulate in m ammalian brain during a relatively short, very critical period, coinci ding with lactation. The accretion of these compounds, metabolically d erived from the essential 18 carbon fatty acids of the two series, n-6 or linoleic acid series, and n-3 or alpha linolenic acid series, is u ltimately dependent upon the dietary supply. The accretion of LCP in b rain may occur through the intake of the precursors followed by conver sion in vivo, or through the intake of preformed compounds. The aim of the study was to explore the ability of nervous cells to synthesize L CP from their precursors in cultured cells, and the possible changes i n the rates of synthesis associated with differentiation. Neuroblastom a cells SK-N-BE, a type of cell which can be induced to differentiate in vitro by retinoic acid (RA), were used. Differentiation was associa ted with reduced cell growth and protein synthesis, and was characteri zed by neurite outgrowth and accumulation of arachidonic acid (AA, 20: 4 n-6). The LCP AA and DHA were produced from the precursors linoleic acid (LA, 18:2 n-6) and eicosapentaenoic acid (EPA, 20:5 n-3) respecti vely, in control cells and in those undergoing differentiation. Conver sion of LA was enhanced at early stages of differentiation, and declin ed when differentiation was completed and accumulation of AA in cell l ipids was maximal. Metabolic changes occurred mainly at the 5 desatura tion reaction, a key step in AA synthesis. Production of DHA from EPA did not change in differentiating cells. Our data indicate that neuron al cells are able to effectively synthesize LCP from precursors, confi rming that the brain is quite self sufficient in the biosynthesis of s tructural lipid components of biomembranes.