Analysis of the putative role of 24-carbon polyunsaturated fatty acids in the biosynthesis of docosapentaenoic (22:5 n-6) and docosahexaenoic (22:6 n-3) acids

The recent literature on the putative involvement of a single cycle of peroxisomal β-oxidation of 24:5 n-6 and 24:6 n-3 polyunsaturated fatty acids in the biosynthesis of the respective docosapentaenoic (22:5 n-6) and docosahexaenoic (22:6 n-3) fatty acids is critically reviewed. Present evidence suggests that in vitro data in support of the above proposition is an artifact of a low 2,4-dienoyl-CoA reductase activity due to depletion of NADPH resulting from incubation conditions. Kinetic studies with radiolabeled precursors in cell cultures have shown lower initial rates of labeling of 24:6 n-3 than that of 22:6 n-3, indicating that 24:6 n-3 is an elongation product of 22:6 n-3 rather than its precursor. Analysis of other literature data supports the proposal that 22:5 n-6 and 22:6 n-3 are synthesized in mitochondria via channeled carnitine-dependent pathways involving separate n-6- and n-3-specific desaturases. It is proposed that impaired peroxisomal function in some peroxisomal disorders is a secondary consequence of defective mitochondrial synthesis of 22:6 n-3; moreover, some disorders of peroxisomal β-oxidation show normal or increased 22:5 n-6 concentrations, indicating that 22:5 n-6 is synthesized by independent desaturases without peroxisomal involvement.