Differences in the interconversion between 20- and 22-carbon (n - 3) and (n - 6) polyunsaturated fatty acids in rat liver.

When male weanling rats were fed diets containing either 5% corn oil or a diet in which half of the corn oil was replaced by fish oil, the 20:5(n - 3) in liver choline and ethanolamine phosphoglycerides, not only partially replaced arachidonate but also paired with palmitic and stearic acids in the same molar ratio as did arachidonate. The 22:5(n - 3)/22:6(n - 3) ratio in the liver phospholipids of corn oil fed rats was similar to that found when the esterified levels of these two acids were increased 5-fold by feeding fish oil. Moreover, the pairing of both 22:5(n - 3) and 22:6(n - 3) with palmitic and stearic acids, on a molar ratio basis, was relatively independent of the total amount of esterified 22:5(n - 3) and 22:6(n - 3). When (3-14C)-labeled 22:4(n - 6) was injected into rats raised on a chow diet or incubated with hepatocytes from these animals, its primary metabolic fate was retroconversion to arachidonate followed by esterification. Conversely, [3-14C]22:5(n - 3) was a poorer substrate for retroconversion with a larger amount being esterified directly into phospholipids and, in addition, this acid served as a precursor for 22:6(n - 3). The enhanced metabolism of both [3-14C]22:4(n - 6) to 22:5(n - 6) and of [3-14C]22:5(n - 3) to 22:6(n - 3) in animals raised on a diet devoid of fat or in their hepatocytes may possibly be due to elevated 6-desaturase activity and/or the level of this enzyme or enzymes. This hypothesis is based on studies showing that the synthesis of 22:6(n - 3) proceeds via a pathway independent of a 4-desaturase but requires the use of a 6-desaturase at two steps (Voss, A., Reinhart, M., Sankarappa, S. and Sprecher, H. (1991) J. Biol. Chem. 266, 19995-20000).