Regulation of the Biosynthesis of 4,7,10,13,16,19-Docosahexaenoic Acid

Abstract

The synthesis of 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) requires that when 6,9,12,15,18,21-tetracosahexaenoic acid (24:6(n-3)) is produced in the endoplasmic reticulum, it preferentially moves to peroxisomes for one cycle of ␤-oxidation rather than serving as a substrate for membrane lipid synthesis. Both 24:6(n-3) and its precursor, 9,12,15,18,21-tetracosapentaenoic acid (24:5(n-3)), were poor substrates for acylation into 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by rat liver microsomes. When peroxisomes were incubated with 1-14 C-or 3- -dienoylCoA isomerase and 2,4-dienoyl-CoA reductase. The accumulation of the substrate for 2,4-dienoyl-CoA reductase, as generated from 22:6(n-3), but not from 20: 5(n-3), suggests that this enzyme distinguishes between subtle structural differences. When 22:6(n-3) is produced from 24:6(n-3), its continued degradation is impaired because of low 2,4-dienoyl-CoA reductase activity. This slow reaction rate likely contributes to the transport of 22:6(n-3) out of peroxisomes for rapid acylation into 1-acyl-GPC by microsomes.

Lipid and fatty acid compositions of a novel docosahexaenoic acid‐producing marine bacterium

“…There is no information on a bacterial synthetic pathway for DHA. It is suggested that the DHA-synthetic pathway for SCRC-21406 is different from that for mammals which involves one turn of the β-oxidation cycle in the peroxisome (17,18). Since the amount of polyunsaturated fatty acids other than DHA is extremely small in SCRC-21406, the pathway also seems to be different from that hypothesized for fungi (19).…”

A Comparison of the Lipid-lowering Effects of Four Different n-3 Highly Unsaturated Fatty Acids in HepG2 Cells

“…As the result, THA 24:6n-3 forms. THA is then β-oxidized to form DHA 23 . Consequently, THA is an n-3HUFA that can be synthesized in humans from EPA.…”

Alternative Sources of n-3 Long-Chain Polyunsaturated Fatty Acids in Marine Microalgae

“…In microalgae, DHA is obtained through EPA elongation into docosapentaenoic acid (DPA) and subsequent desaturation by Δ4 desaturase, or through the anaerobic polyketide synthase (PKS) pathway, as it has been suggested for thraustochytrids [56] and has been inferred in silico for the coccolithophore Emiliania huxleyi Hay and Mohler [4], which are known for their potential to accumulate important amounts of PUFA [57,58]. These pathways are different from the metabolic synthesis of DHA found in animals, known to occur through the Sprecher’s shunt [59]. …”

“…[120], which may be the reason underlying the apparent preferential utilization of the former two in industrial oil production (Table 1). The occurrence of n -6 DPA in lipids of these three species [112,113], though in much lower amounts than DHA, was initially seen as a disadvantage for commercial purposes, especially for neonate nutrition applications [59]. The FDA has considered that, since both n -3 and n -6 DPA are natural components of fish oil, their safety is supported by studies reporting no adverse effects following supplementation with fish or marine oils [119].…”