Talk:Eicosanoid/to do

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[edit] Bringing Eicosanoid up to A level

Some facts about omega;-3 and EFAs that still need to be worked in:

  • Whole controversy about whether or not adults can convert SC-PUFA to LC-PUFA.
  • Differences in affinities of elongase, desaturase, COX and 5-LO between ω-3 and -6.
  • Unlike other eicosanoids, PGI2 and PGI3 seem to act similarly.
  • Why ω-3 feedings that have worked so well in the lab haven't panned out in human trials.
    • Claim that some ecosanoids act differently in humans than mice.

Bringing up to A level:

  • The eicosanoids have such a bewildering set of functions and interactions in the body that they are very difficult to summarize well. What unifies them is their chemical structure. Even that is a little fuzzy - much of the literature claims that all eicosanoids derive from AA. But the interactions with the EPA-derived eicosanoids are very important, and the DGLA-derived ones merit mentioning too.
  • Even so, there needs to be a listing of all the major physiological functions affected by the eicosanoids. Maybe this should be a table.
    • [1] Table 1 would be a good place to start. But even there, he's too focused on the prostaglandins and completely misses the actions in the CNS.
  • The term 'eicosanoid' is somewhat context dependent. Pretty much all the review articles include only the prostanoids and the leukotrienes. But when I go to the literature for the other AA-derived molecules (the lipoxins, hepoxilins, resolvins, EETs...) they all state that they are eicosanoids too. Since the academic literature disagrees, we probably need to get some expert opinion on how to treat those other groups.
  • The introduction: needs to be longer, and to summarize the other sections better. The links and technical terms (paracrine mediator) move to the later sections.
  • Pictures: The existing figure needs a caption. Ideas for other pictures?
  • Missing sections: There are some important issues that the article doesn't address at all:
    • Formation of eicosanoids involves oxygen, and this generates Reactive oxygen species (ROS). Some of the eicosanoids are themselves highly reactive, even mutagenic.
    • The location within the cell of eicosanoid generation, and where and how the eicosanoids travel either into the nucleus or out to the plasma.
    • The evolutionary history of eicosanoids, the suggestion that their signalling function evolved from the function of detoxifying peroxides and other ROS.
    • The article covers eicosanoids in inflammation and immunology. It says almost nothing about the Arachadonic Acid Cascade in neurology and the CNS.
    • Overview or prominent examples of how excesses and deficiencies of eicosanoids result in disease states
    • Use of eicosanoids (and their analogs) as medicines. E.g. alprostadil.
    • How eicosanoids are measured and assayed.
  • The relationship of omega 3/6 fats in the diet to the inflammation balance between the AA and EPA derived eicosanoids is of great general interest. I tried to lay that out in Essential fatty acid interactions but it needs to be at least summarized better here.
  • The high points in eicosanoid research history need to be covered better.
    • Who coined the term eicosanoid, anyhow?
    • Didn't somebody get a Nobel prize?
      DONE -- Nobel prize is mentioned in History section
  • Need a lot more references
  • Most of the material in the section on Receptors needs to be in a table. The section needs an overview. The receptors all are in the same family of receptor proteins, (aren't they)? Discuss where they reside within the cell. The eicosanoids are plietropic - repeatedly, one molecule/receptor pair has been reused to signal vary different things in different tissues.
  • The chemical and physiological distintions between the subclasses of eicosanoid are needed.
  • Other points to make
    • Eicosanoids
  • What is common to all eicosanoids?
    • They're all formed from 20-carbon EFAs that are liberated from cell-wall phospholipids. Cleaving them from the phospholipids is part of the signalling cascade.
    • They are not stored within cells, but are synthesised as required in response to hormonal stimuli.
    • They are formed by the addition of oxygen. (enzymaticly, for the 'classical' ones.)
    • The biologically active forms have short half lives, so they can only act locally. The persistant ones are inactive metabolites.
    • They are signalling molecules. That is, they act by triggering a receptor, rather than by, say, liberating energy or by reacting with a toxin.
    • They signal at very low (nano-molar?) concentrations.
    • There are at least two forms (EPA- and AA-derived) which counterbalance each other. (true at least for the 'classical' eicosanoids - in inflammation. Also true in CNS?)
    • They interact with a particular type of protein (G-coupled?)
    • They are plieotropic; there are many-to many relationships between
      • Stimuli and the production of ecosanoids
      • eicosanoids and their receptors,
      • receptors and functions triggered in different cells.
    • For the 'classical' eicosanoids, they are formed with great stereospecificity. I doubt this is the case for those formed without enzymes, but just by peroxides.

David.Throop 04:38, 6 January 2007 (UTC)

  • Needs a little simplification for readers unfamiliar with the background, especially with the chemistry and the acronyms that have been used.

Ciar 21:33, 7 January 2007 (UTC)