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tisdag 7 mars 2023

Essentiellit rasvahapot AA, EPA ja DHA solukalvoissa.

 AA, C20:4 omega6 (Eicosatetraeenihappo eli  arakidonihappo  C20:4 omega 6 linjasta on lähtöaine eikosanoideille. Linolihappo (LA)   kasvikunnasta johtaa tähän arakidonihappoon kehoentsyymien avulla.
EPA, C20:5 (eicosapentaeenihappo)   omega 3 linjasta.  Alfa-linoleenihappo (ALA) kasvikunnasta johtaa tähän EPA:5  rasvahappoon. 
DHA, C22:6 omega 3 linjasta. Docosahexaeenihappoa muodustuu  jatkossa ihmiskehon entsyymeilä .  
 omega 6 linjasta. Myös  kalarasvoista saa näitä pitkiä rasvahappoja valmiina EPA ja DHA muotoa.

Tiedetään, että ihmisen kaikki  solut, joissa  vain on membraaneja, keräävät membraanin lipidirakenteeseen arakidonihappoa (C20:4), koska  se on lähtöaine  solun monissa funktioissa ja varsinkin kudosten korjaantumisissa ja immuunivasteessa.  Entä sitten  paralleelin  omega3-linjan  rasvahappojen merkitys? Niitäkin solumembraanin  fosfolipidit(PL) keräävät rakenteeseensa ja tämä rasvahappojen valinta  fosfolipidirakenteeseen on  solu- ja kudosspesifistä. Koska nämä kolme pitkää tärkeää essentielliä rakennetta ovat hieman erilaisia ja  koska niiden  kertymiseen vaikuttaa dieetin antamat  essentiellit  linjaa muodostavat  alkumuodot kuten linolihapon (C18:2  omega 6)  ja alfalinoleenihapon (C18:3 omega 3)  saanti, niin mitä tiedeään membraaniaanirakennevaikutuksesta?
 
. 2021;62:100106.
doi: 10.1016/j.jlr.2021.100106. Epub 2021 Aug 13.

EPA and DHA containing phospholipids have contrasting effects on membrane structure

Samuel C R Sherratt  1 , Rebecca A Juliano  2 , Christina Copland  2 , Deepak L Bhatt  3 , Peter Libby  3 , R Preston Mason  4
Affiliations
Free PMC article
Abstract

Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å3 vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0-10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.

Keywords: X-ray diffraction; arachidonic acid; docosahexaenoic acid; eicosapentaenoic acid; membrane structure; omega-3 FAs.


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