Differences in the conversion of the polyunsaturated fatty acids [1-(14)C]22:4(n-6) and [1-(14)C]22:5(n-3) to [(14)C]22:5(n-6) and [(14)C]22:6(n-3) in isolated rat hepatocytes

The reasons why most cellular lipids preferentially accumulate 22:6(n-3) rather than 22:5(n-6) are poorly understood. In the present work the metabolisms of the precursor fatty acids, [1-(14)C]20:4(n-6), [1-(14)C]22:4(n-6) versus [1-(14)C]20:5(n-3), [1-(14)C]22:5(n-3) in isolated rat hepatocytes were compared. The addition of lactate and L-decanoylcarnitine increased the formation of [(14)C]24 fatty acid intermediates and the final products, [(14)C]22:5(n-6) and [(14)C]22:6(n-3). In the absence of lactate and L-decanoylcarnitine, no [(14)C]24 fatty acids and [(14)C]22:5(n-6) were detected when [1-(14)C]22:4(n-6) was the substrate, whereas small amounts of the added [1-(14)C]22:5(n-3) was converted to [(14)C]22:6(n-3). Lactate reduced the oxidation of [1-(14)C]22:4(n-6) and [1-(14)C]22:5(n-3) while L-decanoylcarnitine did not. No significant differences between the total oxidation or esterification of the two substrates were observed. By fasting and fructose refeeding the amounts of [(14)C]24:4(n-6) and [(14)C]24:5(n-3) were increased by 2.5- and 4-fold, respectively. However, the levels of [(14)C]22:5(n-6) and [(14)C]22:6(n-3) were similar in hepatocytes from fasted and refed versus fed rats. With hepatocytes from rats fed a fat free diet the levels of [(14)C]24 fatty acid intermediates were low while the further conversion of the n-6 and n-3 substrates was high and more equal, approx. 33% of [1-(14)C]22:4(n-6) was converted to [(14)C]22:5(n-6) and 43% of [1-(14)C]22:5(n-3) was converted to [(14)C]22:6(n-3). The moderate differences found in the conversion of [1-(14)C]22:4(n-6) versus [1-(14)C]22:5(n-3) to [(14)C]22:5(n-6) and [(14)C]22:6(n-3), respectively, and the equal rates of oxidation of the two substrates could thus not explain the abundance of 22:6(n-3) versus the near absence of 22:5(n-6) in cellular membranes.