Regulation of the biosynthesis of 22:5n‐6 and 22:6n‐3: A complex intracellular process

Abstract

Both 22:4n-6 and 22:5n-3 are synthesized from n-6 and n-3 fatty acid precursors in the endoplasmic reticulum. The synthesis of both 22:5n-6 and 22:6n-3 requires that 22:4n-6 and 22:5n-3 are metabolized, respectively, to 24:5n-6 and 24:6n-3 in the endoplasmic reticulum. These two 24-carbon acids must then move to peroxisomes for partial degradation followed by the movement of 22:5n-6 and 22:6n-3 back to the endoplasmic reticulum for use as substrates in membrane lipid biosynthesis. Clearly an understanding of the control of intracellular fatty acid movement as well as of the reactions carried out by microsomes, peroxisomes, and mitochondria are all required in order to understand not only what regulates the biosynthesis of 22:5n-6 and 22:6n-3 but also why most tissue lipids selectively accumulate 22:6n-3.

Fatty Acid Transport Protein 4 Is the Principal Very Long Chain Fatty Acyl-CoA Synthetase in Skin Fibroblasts

“…The final double bond is introduced by a ⌬6 desaturase, yielding C24:63, after which a single round of peroxisomal ␤-oxidation removes two carbons, yielding C22:63 (48). An analogous pathway has been proposed for the conversion of C22:46 to C22:56 (49). It is thus a possibility that FATP4 deficiency decreases flux through the required ␤-oxidation step.…”

“…This suggests the possibility that FATP4 may be important for fatty acid elongation pathways, perhaps by providing substrates for polyunsaturate-specific elongases such as ELOVL2, 4, or 5 (47). In addition, the normal pathway for synthesis of C22:56 and C22:63 requires not only elongation but peroxisomal ␤-oxidation (48,49). Mammals lack the ⌬4 desaturase needed to convert C22:53 to C22:63.…”

Isolation and functional characterization of fatty acid Δ5‐elongase gene from the liverwort Marchantia polymorpha L

“…2a and b). GC-MS analysis of methyl esters of these fatty acids showed that their spectra were identical to those of authentic docosatetraenoic acid (DTA, 22:4D 7,10,13,16 ) and DPA, respectively, demonstrating that the novel peaks were D5-elongated products of the supplemented fatty acids (Fig. 2).…”

“…Very-long-chain polyunsaturated fatty acids (VLCPUFAs) represented by arachidonic acid (AA; 20:4D 5,8,11,14 ), eicosapentaenoic acid (EPA; 20:5D 5,8,11,14,17 ), and docosahexaenoic (DHA; 22:6D 4,7,10,13,16,19 ) acid are widely recognized, because of their beneficial roles in human health. In particular, DHA is an essential component of membrane lipids of brain neurons, testes, and the external segments of photoreceptors in the retina [1].…”

“…In mammals, the conversion of EPA into DHA occurs through the Sprecher pathway, which involves two elongations, a desaturation, and a b-oxidation step [6,7]. In lower eukaryotes, DHA is synthesized more simply by D5-elongation from EPA to docosapentaenoic acid (DPA, 22:5D 7,10,13,16,19 ), followed by D4-desaturation. To date, D4-desaturase genes have been identified from a marine fungus and several microalgae [8][9][10][11].…”