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tisdag 23 januari 2018

Mead haposta engl. tekstiä

 Mead acid is an omega-9 fatty acid, first characterized by James F. Mead.[1] As with some other omega-9 polyunsaturated fatty acids, animals


Wikipedian englantilaisesta versiosta löytyy enemmänkin  matabolista kartata Meadin haposta  

yleensä syklo-oxygenaasientsyymit  otavat substraatikseen arakidonihapon kun oksidoivat tulehduksissa  siitä  vaikuttavia aineita,kuten  PGH2   prostaglandiinia H2. Meadin happo muistuttaa arakidonia sikäli että siinä on 20 hiiltä ja ainakin 3 kaksoissidosta, joten  se  tarjoaa sellaista rakennetta, jota entsyymi voi käyttää arakidonihapon puutteessa. Meadin happo voi konvertoitua leukotrieeneksi  LTC3 ja LTD3.

Myös entyymi 5-lipoxygenaasi  voi  modifioida  Meadin happoa ja tekee siitä 5-hydroxy-eikosatrieenihappoa (5-HETrE). 

Entsyymi 5-hydroxyeikosanoididehydrogenaasi voi muuttaa sen sitten  5-oxoeikosatrieenihapoksi (5-oxo-ETrE). Tämä  metaboliitti taas on yhtä  vahva vaikuttaja  kuin sen arakidonihaposta tullut analogi  5-oxoeikosatetraeenihappo (5-oxo-ETE). Tässä vertaillaan niiden vaikutusta  stimuloida ihmisen veren eosinofiilejä ja neutrofiilejä. On ilmeistä että  Meadin haposta tuleva  15-oxo-ETrE käyttää  samaa reseptoria kuin arakidonihaposta tuleva analogi: nimittäin reseptoria OXER1  ja ehkä sen takia se on  kuin   analoginsa , ihmisen allergisten ja inflammatoristen reaktioiden  välittäjä.

Role in inflammation

Cyclooxygenases are enzymes known to play a large role in inflammatory processes through oxidation of unsaturated fatty acids. Most notably, the formation of prostaglandin H2 from arachidonic acid which is very similar in structure to mead acid. When physiological levels of arachidonic acid are low, other unsaturated fatty acids including mead and linoleic acid are oxidized by COX.
Mead acid is also converted to leukotrienes C3 and D3.[8]
Mead acid is metabolized by 5-lipoxygenase to 5-hydroxyeicosatrieonic acid (5-HETrE)[9] and then by 5-Hydroxyeicosanoid dehydrogenase to 5-oxoeicosatrienoic acid (5-oxo-ETrE).[10] 5-Oxo-ETrE is as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), in stimulating human blood eosinophils and neutrophils;[11] it presumably does so by binding to the 5-oxo-ETE receptor (OXER1) and therefore may be, like 5-oxo-ETE, a mediator of human allergic and inflammatory reactions
  • Tietoja OXER1 reseptorista.
 https://en.wikipedia.org/wiki/Oxoeicosanoid_receptor_1

OXER1-reseptorin sijainti on kromosomissa 2p21.  Se on g-proteiiniin kytkeytynyt rseptori 170 (GPR170)  ja se on pääasiassa arakidonihaposta johtuvan karboksyylihappometaboliitin  5-HETEpääasiallinen reseptori.
Mielenkiintoinen kappale! Kuitenkin lopuksi sanotaan että tiedot ovat  toistaiseksi prekliinisiä.

 Oxoeicosanoid receptor 1 (OXER1) also known as G-protein coupled receptor 170 (GPR170) is a protein that in humans is encoded by the OXER1 gene located on human chromosome 2p21; it is the principle receptor for the 5-Hydroxyicosatetraenoic acid family of carboxy fatty acid metabolites derived from arachidonic acid.[3][4][5] The receptor has also been termed hGPCR48, HGPCR48, and R527 but OXER1 is now its preferred designation


 To date, however, all studies have been pre-clinical; they use model systems that can suggest but not prove the contribution of OXER1 to human physiology and diseases. The most well-studied and promising area for OXER1 function is in allergic reactions. The recent development of OXER1 antagonists will help address this issue.

1 kommentar:

  1. Aldehyde dehydrogenase from yeast catalyzes the following reaction: RCHO + NAD/NADP+ + H2O → RCOOH + NADH/NADPH+ + H+. The yeast enzyme requires potassium ions and thiols (glutathione, aldehyde dehydrogenase

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