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

The reasons why most cellular lipids preferentially accumulate 22:6(n-3) ra ther than 22:5(n-6) are poorly understood. In the present work the metaboli sms of the precursor fatty acids, [1-C-14]20:4(n-6), [1-C-14]22:4(n-6) vers us [1-C-14]20:5(n-3), [1-C-14]22:5(n-3) in isolated rat hepatocytes were co mpared. The addition of lactate and L-decanoylcarnitine increased the forma tion of [C-14]24 fatty acid intermediates and the final products, [C-14]22: 5(n-6) and [C-14]22:6(n-3). In the absence of lactate and L-decanoylcarniti ne, no [C-14]24 fatty acids and [C-14]22:5(n-6) were detected when [1-C-14] 22:4(n-6) was the substrate, whereas small amounts of the added [1-C-14]22: 5(n-3) was converted to [C-14]22:6(n-3). Lactate reduced the oxidation of [ 1-C-14]22:4(n-6) and [1-C-14]22:5(n-3) while L-decanoylcarnitine did not. N o significant differences between the total oxidation or esterification of the two substrates were observed. By fasting and fructose refeeding the amo unts of [C-14]24:4(n-6) and [C-14]24:5(n-3) were increased by 2.5- and 4-fo ld, respectively. However, the levels of [C-14]22:5(n-6) and [C-14]22:6(n-3 ) were similar in hepatocytes from fasted and refed versus fed rats. With h epatocytes from rats fed a fat free diet the levels of [C-14]24 fatty acid intermediates were low while the further conversion of the n-6 and n-3 subs trates was high and more equal, approx. 33% of [1-C-14]22:4(n-6) was conver ted to [C-14]22:5(n-6) and 43% of [1-C-14]22:5(n-3) was converted to [C-14] 22:6(n-3). The moderate differences found in the conversion of [1-C-14]22:4 (n-6) versus [1-C-14]22:5(n-3) to [C-14]22:5(n-6) and [C-14]22:6(n-3), resp ectively, 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. (C) 2001 Elsevier Science B.V. All rights reserved .