Heneicosapentaenoate (21:5n−3): Its incorporation into lipids and its effects on arachidonic acid and eicosanoid synthesis

Abstract

6,9,12,15,18-Heneicosapentaenoic acid (21:5n-3) (HPA), present in small amounts in fish oils, has been prepared by chemical elongation of eicosapentaenoic acid (EPA) and its biological properties compared with EPA and docosahexaenoic acid (DHA). All the double bonds of HPA are displaced one carbon away from the carboxyl group when compared to EPA. HPA is incorporated into phospholipids and into triacylglycerol in cell culture to a similar extent as EPA and DHA. HPA is a stronger inhibitor of the conversion of alpha-linoleic acid and dihomo-gamma-linolenic acid to arachidonic acid (AA) in hepatoma cells than are EPA, DHA, and AA. HPA is a poor substrate for prostaglandin H synthase and for 5-lipoxygenase, but it inactivates prostaglandin H synthase as rapidly as do AA, EPA, and DHA. HPA inhibits thromboxane synthesis in isolated platelets as efficiently as EPA. EPA, HPA, and DHA are all weak inducers of acyl-CoA oxidase in hepatoma cells. Therefore, since fish oils contain only small amounts of HPA, it is unlikely that this fatty acid is of particular significance for the biological effects of these oils, possibly with the exception that it is a strong inhibitor of AA synthesis.

2-Hydroxy-Docosahexaenoic Acid Is Converted Into Heneicosapentaenoic Acid via α-Oxidation: Implications for Alzheimer’s Disease Therapy

“…In accordance with the results reported here, α-oxidation appears to be the main pathway involved in DHA-H metabolism leading to HPA, via an intermediated fatty aldehyde (Foulon et al, 2005;Jansen and Wanders, 2006). HPA produced by DHA-H α-oxidation can then follow 2 pathways: cell accumulation as part of complex lipids like phospho-or glycerolipids (Larsen et al, 1997), or catabolism via β-oxidation. Our results demonstrate that at least part of the HPA produced accumulates in a concentration-and timedependent manner (see Figure 1C), mostly as PC species (see Supplementary Table S1).…”

Structural elucidation of molecular species of pacific oyster ether amino phospholipids by normal-phase liquid chromatography/negative-ion electrospray ionization and quadrupole/multiple-stage linear ion-trap mass spectrometry

“…8a) at m / z 315 (abundant; the sn -2-21:5), m / z 255 (weak; the sn -1-16:0) and m / z 452 [750-R′ 2–3 -CH═C═O] − ([750 – (315 – 17)] − ) further suggest the existence of the two diacyl species 17:0/20:5 PE and 16:0/21:5 PE. The presence of a small amount of heneicosapentaenoic acid (21:5 (ω-3) or Δ 6,9,12,15,18) has been reported in marine animals [9–13,46]. …”

100 Years of the Wolff Rearrangement

“…[401] all-cis-Heneicosa- 6,9,12,15,18-pentaenoic acid was also prepared by way of ArndtϪEistert reaction (PhCO 2 Ag, 70%), in order to compare its biological properties with those of homologous acids present in fish oil. [402] Arenecarboxylic acids with a variety of substitution patterns were homologated in an effort to optimize the GnRH antagonist 435 (Scheme 52). [403] The ArndtϪEistert reaction was successfully applied to 2Ј-methoxy-1,1Ј-binaphthyl-2-carboxylic acid (Ag 2 O, EtOH, 60Ϫ70°C, 82%).…”