Metabolism of polyunsaturated fatty acids by rabbit reticulocytes

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Abstract
Rabbit reticulocytes obtained by repeated bleeding metabolize exogenous [1‐14C]linoleic acid and [1‐14C]arachidonic acid by three different pathways. 1 Incorporation into cellular lipids: 50% of the fatty acids metabolized are incorporated into phospholipids, mainly phosphatidylcholine (32.8%) but also into phosphatidylethanolamine (12%), whereas about 10% of the radioactivity was found in the neutral lipids (mono‐ di‐ and triacylglycerols, but not cholesterol esters). 2 Formation of lipoxygenase products: 30% of the fatty acids metabolized are converted via the lipoxygenase pathway mainly to hydroxy fatty acids. Their formation is strongly inhibited by lipoxygenase inhibitors such as 5,8,11,14‐eicosatetraynoic acid or nordihydroguaiaretic acid. Inhibition of the lipoxygenase pathway results in an increase of the incorporation of the fatty acids into cellular lipids. 15‐Hydroxy‐5,8,11,13(Z,Z,Z,E)eicosatetraenoic acid and 13‐hydroxy‐9,11(Z,E)‐octadecadienoic acid are incorporated by reticulocytes into cellular lipids and also are metabolized via β‐oxidation. The metabolism of arachidonic acid and linoleic acid is very similar except for a higher incorporation of linoleic acid into neutral lipids. 3 β‐Oxidation of the exogenous fatty acids: about 10% of the polyenoic fatty acids are metabolized via β‐oxidation to 14CO2. Addition of 5,8,11,14‐eicosatetraynoic acid strongly increased the 14CO2 formation from the polyenoic fatty acids whereas antimycin A completely abolished β‐oxidation. Erythrocytes show very little incorporation of unsaturated fatty acids into phospholipids and neutral lipids. Without addition of calcium and ionophore A23187 lipoxygenase metabolites could not be detected.