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

Abstract

The recent literature on the putative involvement of a single cycle of peroxisomal L L-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 L L-oxidation show normal or increased 22:5n-6 concentrations, indicating that 22 :5n-6 is synthesized by independent desaturases without peroxisomal involvement.z 1998 Federation of European Biochemical Societies.

In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method

“…It appeared then that 20:4n-6 substrate was more efficiently elongated when it had a history of sequential elongation/desaturation (i.e., 13 C-20:4n-6 derived from 13 C-18:2n-6) than when it had more recently entered the metabolic pathway. This is consistent with previous reports of a channeling concept for coupled fatty acid elongation/desaturation systems (46), perhaps by a multienzyme complex (47).…”

Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults

“…Docosapentaenoic acid (22:5n-3, DPAn-3) is synthesized from EPA by addition of C 2 . The conversion of DPAn-3 to DHA has been a matter of controversy and ∆4-desaturase activity has been suggested to be the primary mechanism for DHA synthesis [39]. However, of studies in which subcellular organelles were isolated and then recombined [40] and reports of the action of the specific ∆6-desaturase inhibitor SC-26196 [41] strongly support the suggestion that synthesis of DHA involves desaturation at the ∆6-position as follows.…”

A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids

“…FADS are known to be ER proteins, but some evidence suggests they are active in other organelles, especially mitochondria ( 32,33 ). To determine the subcellular localization of FADS1CS (444 amino acids) and FADS1AT1 (360 amino acids), we performed experiments using GFP tagging system.…”

“…It is well known that desaturation and elongation steps localize to the ER ( 52 ), but they have been suggested over the years to occur in other organelles as well ( 32 ). Data implicating mitochondrial involvement in 22:6n-3 biosynthesis by guest, on May 10, 2018 www.jlr.org Downloaded from similar to SCD was identifi ed.…”