Analysis of the putative role of 24-carbon polyunsaturated fatty acids in the biosynthesis of docosapentaenoic (22:5n-6) and docosahexaenoic (22:6n-3) acids.
The recent literature on the putative involvement of a single cycle of peroxisomal beta-oxidation of 24:5n-6 and 24:6n-3 polyunsaturated fatty acids in the biosynthesis of the respective docosapentaenoic (22:5n-6) and docosahexaenoic (22:6n-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 24:6n-3 than that of 22:6n-3, indicating that 24:6n-3 is an elongation product of 22:6n-3 rather than its precursor. Analysis of other literature data supports the proposal that 22:5n-6 and 22:6n-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 22:6n-3; moreover, some disorders of peroxisomal beta-oxidation show normal or increased 22:5n-6 concentrations, indicating that 22:5n-6 is synthesized by independent desaturases without peroxisomal involvement.
Institute for Theoretical Biochemistry and Molecular Biology, Ithaca, NY 14852-4512, USA.
J P
JP
Infante
V A
VA
Huszagh
D000818:Animals; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000378:metabolism
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; C026219:docosapentaenoic acid