Differences in the conversion of the polyunsaturated fatty acids [1-14C]22:4(n–6) and [1-14C]22:5(n–3) to [14C]22:5(n–6) and [114C]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, [1-14C]20:4(n–6), [1-14C]22:4(n–6) versus [1-14C]20:5(n–3), [1-14C]22:5(n–3) in isolated rat hepatocytes were compared. The addition of lactate and -decanoylcarnitine increased the formation of [14C]24 fatty acid intermediates and the final products, [14C]22:5(n–6) and [14C]22:6(n–3). In the absence of lactate and -decanoylcarnitine, no [14C]24 fatty acids and [14C]22:5(n–6) were detected when [1-14C]22:4(n–6) was the substrate, whereas small amounts of the added [1-14C]22:5(n–3) was converted to [14C]22:6(n–3). Lactate reduced the oxidation of [1-14C]22:4(n–6) and [1-14C]22:5(n–3) while -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 [14C]24:4(n–6) and [14C]24:5(n–3) were increased by 2.5- and 4-fold, respectively. However, the levels of [14C]22:5(n–6) and [14C]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 [14C]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 [1-14C]22:4(n–6) was converted to [14C]22:5(n–6) and 43% of [1-14C]22:5(n–3) was converted to [14C]22:6(n–3). The moderate differences found in the conversion of [1-14C]22:4(n–6) versus [1-14C]22:5(n–3) to [14C]22:5(n–6) and [14C]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.