Talk:Eicosanoid

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Contents

[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)


[edit] Accuracy

This article is a very good piece of work and shows a lot of research. But let me offer a correction. It repeatedly states that all eicosanoids are derived from arachadonic acid. This is incorrect.

  • The series-2 prostaglandins (PG) and thromboxanes (TX) are derived from arachadonic acid.
  • The series-1 PG and TX are derived from Gamma-linolenic acid through the DGLA intermediary.
  • The series-3 PG and TX are derived from EPA.

I'm not sure about the prostacyclins and the leukotrienes. Also, arachadonic acid has other uses in the body besides eicosanoids, e.g. as a substrate for the endocannabinoids. David Throop 25 Oct 2005

Also, the article states that the eicosanoids are a class of cytokines. But the cytokine article says that cytokines are proteins. And eicosanoids aren't proteins; they don't even have any nitrogen in their structure.

David Throop 13 Nov 2005

[edit] EETs

I think that there is a third way of arachidonic acid metabolism, called epoxygenase.

Yes, there is, the EETs, via the Cytochrome P450 path. I'd noted it but haven't read enough about it to say anything interesting. I've added a link for it, but there's nothing there yet. I also added a link to a future article on Neuroprotectin D, which is AA derived. Does anybody know more about the EETs? Particularly, does anybody know if they only come from AA, or is there an EPA derived subfamily for them too?David.Throop 15:02, 12 March 2006 (UTC)

[edit] General discussion

This page looks good. I've never studied this topic, so there's not much that I can say about it. It might be nice to add some diagrams of molecular structures. I know that Canvas is a good program for this, but I won't be able to draw them any time soon. Do you know anything about the receptors for these hormones? I'm going on a Wiki-vacation, so I won't be available for more input for a while. Keep up the good work! AdamRetchless 08:15, 4 May 2004 (UTC)

My source has quite a bit on the receptors, but they are quite specific for leukotrienes, prostacyclin etc. I thought it would be better to include this in the related articles, rather than on eicosanoid proper.
JFW | T@lk 09:28, 4 May 2004 (UTC)

I just wanted to say, completely out of place really, that I am totally in awe of whoever made that brilliant diagram with all the links in it. People like you are exactly what the world needs more of. Wikipedia just blows me away.

[edit] Grammar

Is "that largely function as a autocrine and" supposed to refer to a chemical known as "a autocrine"? Perhaps it should be in italics -- it looks like a grammar error, but I am not sure if it is one. Cleduc 1 July 2005 19:46 (UTC)

[edit] Cleanup

Someone asked for cleanup, because:

This article is a very good piece of work and shows a lot of research. But let me offer a correction. It repeatedly states that all eicosanoids are derived from arachadonic acid. This is incorrect. The series-2 prostaglandins (PG) and thromboxanes (TX) are derived from arachadonic acid. The series-1 PG and TX are derived from Gamma-linoleic acid through the DGLA intermediary. The series-3 PG and TX are derived from EPA. I'm not sure about the prostacyclins and the leukotrienes. Also, arachadonic acid has other uses in the body besides eicosanoids, e.g. as a substrate for the endocannabinoids.

This is not good use of cleanup. Cleanup is when the fact are correct but presented clumsily. If you think the facts are incorrect, fix it! JFW | T@lk 20:51, 26 October 2005 (UTC)

[edit] References?

This article seems to be more or less accurate, but it needs to be properly referenced.--Virulent 78 13:49, 4 February 2006 (UTC)

I'll find a few, but with M.W. King's site linked I guess we don't need the {{unreferenced}} template anymore. JFW | T@lk 05:16, 5 February 2006 (UTC)

<SNIP!>

removed the text that just repeated what I'd said in the Comments page...

[edit] Request for Help drawing some Pictures

There are two diagrams (figures 1 and 2) in

that I'd really like to have for the Eicosanoid page. I've read a lot of eicosanoid papers and these are by fat the best diagrams I've seen.

They need to be updated a little – some more research has come in since they were published. Is anybody listening who is a good graphic artist and would someone like to work with me on this? – David.Throop 23:22, 10 January 2007 (UTC)

[edit] Major Updates

I've brought material from Essential fatty acid interactions; it's a better fit here, I think. I've put Ciar's pictures into a single figure and added captioning. I've put the list of receptors in a table, and added another table of eicosanoid medicines. Introduced a section on eicosanoids in inflammation.

I used the wikitable template, which is mostly good. But the body text runs right up against the table (in my browser, Firefox.) If anybody can jiggle the handle on the tables so they don't do that I'd be obliged.David.Throop 15:00, 13 January 2007 (UTC)

[edit] Hi there

Excellent work. As a note for the future, using the Bookmarklet as detailed on this page makes adding references as easy as cut and paste. It adds into your browser as a button you can click and it pops up a window summarising the PubMed entry you are looking at in the correct format to paste into Wikipedia. TimVickers 18:08, 13 January 2007 (UTC)

[edit] protein cofactor?

Help! Near the end of the Nomenclature section, I disambiguated "cofactor" to "cofactor (biochemistry)", but we now have the phrase "protein cofactor" linking to a definition which specifically states "non-protein"! It seems to me that either the Eicosanoid page or the cofactor (biochemistry) page needs to be edited by someone with knowledge of whether cofactors can be protein or not. (perhaps the cofactor page needs to say "usually non-protein"?) --Coppertwig 17:24, 27 January 2007 (UTC)

A quick trip to scholar.google.com showed that most scholarly works were calling FLAP an enzyme or a co-enzyme. So I made that change. David.Throop 17:55, 27 January 2007 (UTC)
Well done. --Coppertwig 01:17, 31 January 2007 (UTC)

[edit] Biosynthesis

I find the table a little confusing. It says there are two pathways for free fatty acids, and then it says there are also additional pathways. Could it be made clear what it is about these additional pathways that precludes them from being included in the original count of two? Is it because they don't begin with free fatty acids? Is it because they involve oxygenation, while the original two perhaps don't? Is it because the first two are commonly called eicosanoids, while the others are only "technically" eicosanoids? Is it because all of the "other" pathways produce products with a number of carbon atoms not equal to 20? Any of these could be inferred from the table. Whatever is actually meant should be more clearly stated.

OK, someone has fixed it. It's fine now. It contrasts "classical" eicosanoids with "other ...20-carbon..." and has a few other little fixes such as putting eicosanoids in italics in one place which just make the table quite clear to me now. Thanks. --Coppertwig 01:34, 2 February 2007 (UTC)

Also, this article should decide exactly which molecules it is or is not calling "eicosanoids". For example, in the introduction, it could say something like "x, y and z are also technically eicosanoids but, following the more common convention, will not be referred to as eicosanoids in this article." I don't much care which convention is followed in the article as long as it's clear to the reader which naming convention is being followed, and all very common conventions are mentioned in the introduction. When the "other" molecules are mentioned it could say "not classified here as eicosanoids" or "not called eicosonoids here" or "not universally referred to as eicosanoids". (sorry I can't think of a shorter phrase for that.) --Coppertwig 14:47, 28 January 2007 (UTC)

Coppertwig, thanks for some good, pointed observations. The problem is that the field doesn't seem to have reache a consensus. Not only that, they don't even seem to be arguing about it -- there are just a bunch of different authors using the terms in similar but distinct ways. The review articles just state that the eicosanoids comprise the prostanoids and the leukotrienes. Then I read the articles on the EETs, lipoxins etc and they just state that these compounds are eicosanoids. Nobody AFAIK has proposed an alternative nomenclature. I'm thinking that I'll need to email a few of the prominent authors; maybe they can point me to someplace where this has already been hashed out. I will get this straighter before I put it up for Good/Featured Article review, tho.
A related issue is that about half the articles claim that all eicosanoids derive from arachidonic acid and completely ignore the series from EPA and DGLA. But I've just decided to omit that. David.Throop 21:28, 29 January 2007 (UTC)
In my opinion, you can more-or-less arbitrarily choose one definition, state that it's the definition being used in this article, and then use it consistently throughout the article. For example, one table states that "all eicosanoids" have corresponding receptors. If you haven't clarified what "eicosanoids" means in this article, such a statement is confusing, meaningless and likely misleading.
One way to choose a definition is to take the approximate median of the definitions used by the sources: that is, to include a molecule as an eicosanoid in your definition if approximately half or more of the authors would include it. The definition should however also be simple, logical and identical to the definition used by at least one author.
Another approach is to look at the etymology of the word, i.e. to use the definition used by whoever invented the word in the first place (and it would be good to name this person in the article, anyway). However, if that definition is not now a common usage that might not be a good approach.
The definition of "eicosanoid" is crucial, among other reasons because it defines what subject matter this article is supposed to be covering. --Coppertwig 13:49, 1 February 2007 (UTC)
I suggest editing part of the Nomenclature section to read:
Current usage limits this to the leukotrienes (LT) and three types of prostanoids—prostaglandins (PG) prostacyclins (PGI), and thromboxanes (TX), and this is the definition used in this article, although several other classes could technically be termed eicosanoid, including the hepoxilins, resolvins, isofurans, isoprostanes, lipoxins, epoxyeicosatrienoic acids (EETs) and some endocannabinoids. - good. accepted. -drt
(I inserted "and this is the definition used in this article", and changed "but" to "although", and "are technically" to "could technically be termed"). I think that would clear up the current ambiguity (provided the rest of the article does actually conform to that definition). --Coppertwig 14:39, 1 February 2007 (UTC)

The first two sentences of the "biosynthesis" section, and perhaps most or all of the first paragraph of the biosynthesis section, is merely a repeat of information already given in the introduction and needs to be deleted. If there is any important information in this paragraph it would be better moved elsewhere, e.g. fit it in later in the biosynthesis section or in another section; the beginning of what is now the second paragraph of the biosynthesis section would be a better lead-in to this topic. The first paragraph seems to be more about usage and breakdown than synthesis. --Coppertwig 14:55, 28 January 2007 (UTC)

Here is an edit of the paragraph beginning "The first step...". I've attempted to improve the style (flow of language), for example trying to eliminate parentheses if possible. However, this paragraph still has this problem: animals do not have "cell walls"!!

The first step of eicosanoid biosynthesis occurs when a cell is activated by mechanical trauma, cytokines, growth factors, an eicosanoid from a neighboring cell or some other stimulus, which triggers the release of a phospholipase at the cell wall. This phospholipase (either A2 or C) travels to the nuclear membrane, where it catalyzes ester hydrolysis of a phospholipid (by A2) or of diacylglycerol (by phospholipase C). This hydrolysis reaction frees a 20-carbon essential fatty acid and appears to be the rate-determining step for eicosanoid formation.

I'm editing for clarity and flowing language here; please check that I haven't mangled the facts. --Coppertwig 15:23, 28 January 2007 (UTC)

Woops: the second-last paragraph of the biosynthesis section (both the current version and my version above) implies that there are only two possible types of phospholipase involved, while the following paragraph says there are "several" possible types; to me "several" suggests at least three. It doesn't actually list more than two examples, though, and it also seems to say that one particular type, cPLA2, is absolutely needed, ("... devoid ...") so maybe there's really only one? Clarification needed. --Coppertwig 16:13, 28 January 2007 (UTC)

[edit] Peroxydation section

The first sentence of the last paragraph sounds anticlimactic to me on first reading:

The generation of lipid hydroperoxides within or near the cell nucleus must confer a benefit.

It seems to be saying that something which has already been positively stated earlier may be true, i.e. that "The generation of lipid hydroperoxides ... must confer a benefit". This sentence can be made stronger by increasing the emphasis on the site at which the reaction occurs. For example, by changing it to:

The site of the generation of lipid hydroperoxides, within or near the cell nucleus, must confer a benefit. or
The location of generation of lipid hydroperoxides within or near the cell nucleus must confer a benefit."

or "siting" or "positioning" instead of "location", etc. --Coppertwig 16:33, 28 January 2007 (UTC)

OK, changed it to
The cell must realize some benefit from generating lipid hydroperoxides close-by its nucleus. PGs and LTs may signal or regulate DNA-transcription there; LTB4 is ligand for PPARα.
Better? David.Throop 21:13, 29 January 2007 (UTC)
Yes, I think that's fine. The slightly different rhythm of the sentence carries it, I think. Thanks. --Coppertwig 01:14, 30 January 2007 (UTC)

I changed "oxidation proceeds with high stereospecificity" to "oxidation reaction introduces stereospecificity". First of all, it seems to me that a molecule is either stereospecific or it's not; the word "high" seems unnecessary. Secondly, I believe the reaction begins with two stereononspecific molecules, therefore it seems to me that the reaction ends with stereospecificity but it is not necessarily accurate to say that it "proceeds" with stereospecificity. --Coppertwig 01:44, 2 February 2007 (UTC)

I think you've misunderstood the term 'stereospecific', it's a feature of the reaction, not the molecule. 'The reaction proceeds with great stereospecificity' means that it produces only one of the possible chiral products. If it has low stereospecificity, you get nearly a racemic mixture. Follow the link to stereospecificity for more. David.Throop 01:56, 2 February 2007 (UTC)

[edit] Image

I drew the diagram of eicosanoid synthesis. If there are adjustments to be made, please let me know. I can also release the sxd file (OpenOffice.Org) for others to fiddle with. JFW | T@lk 20:43, 29 January 2007 (UTC)

[edit] biosynthesis of prostanoids

The terminology needs to be made more clear and consistent between the paragraph and the diagram. It says "can be seen in the diagram," but I don't see in the diagram the things that are mentioned in the paragraph. The paragraph says "PGH" (what is that?); I don't see the label "PGH" in the diagram. The paragraph describes a number of molecules with rings, but two of the molecules in the diagram do not seem to have rings. Which of the molecules in the diagram are "PGH compounds"? Which are "the rest"? Which are "derived prostaglandins"? Which are "thromboxanes"? I really can't match a single molecule in the diagram to a single reference in the paragraph. The reader should be able to understand the paragraph and related diagram without having to go back and reread and study the earlier section of the article. I hope this doesn't sound too critical; I'm trying to be helpful here. --Coppertwig 02:42, 30 January 2007 (UTC)

OK, I think I can mostly fix this, but someone will have to check that I haven't mangled any of the science. It said:

All three classes of prostanoids originate from PGH. All have distinctive rings in the center of the molecule. They differ in their structures. As the Structures of Selected Eicosanoids figure shows, the PGH compounds (parents to all the rest) have a 5-carbon ring, bridged by two oxygens (a peroxide.) The derived prostaglandins contain a single, unsaturated 5-carbon ring. In prostacyclins, this ring is conjoined to another oxygen-containing rings. In thromboxanes the ring becomes a 6-member ring with one oxygen. (See more detail, including the enzymes involved, in diagrams at Prostanoid.)

I'm changing it to:

All three classes of prostanoids originate from PGH. All have distinctive rings in the center of the molecule. They differ in their structures. The PGH compounds (parents to all the rest) have a 5-carbon ring, bridged by two oxygens (a peroxide.) As the example in Structures of Selected Eicosanoids figure shows, the derived prostaglandins contain a single, unsaturated 5-carbon ring. In prostacyclins, this ring is conjoined to another oxygen-containing ring. In thromboxanes the ring becomes a 6-member ring with one oxygen. The leukotrienes do not have rings. (See more detail, including the enzymes involved, in diagrams at Prostanoid.)

My purpose here is to make the paragraph seem to match what is shown in the figure. If I understand this paragraph correctly, PGH compounds (not shown in the figure) have an oxygen bridge in the ring, while prostaglandins do not. Please check that the paragraph as I've edited it has not become incorrect. --Coppertwig 02:08, 2 February 2007 (UTC)

[edit] Only arachidonic acid?

Someone mentioned above that arachidonic acid is not the only source of eicosanoids. The first diagram at the top of the article shows only arachidonic acid, so maybe it needs to be changed (or labelled as being an example). --Coppertwig 02:45, 30 January 2007 (UTC)

[edit] References format

Changing the reference style has greatly improved the page. I have added the following:

<div class="references-small" style="-moz-column-count:2; column-count:2;"> <references/> </div>

To convert from single-column to two-column format (it looks much nicer) but alas this will not display as such in every browser. (I believe it works in Firefox). If someone knows how to make it display in two columns in all browsers, please tell me how! Thanks in advance István 17:48, 30 January 2007 (UTC)

[edit] "The ω-3 and ω-6 series" subsection

The reduction in AA-derived eicosanoids and the diminished activity of the alternative products generated from ω-3 fatty acids serve as the foundation for explaining some of the beneficial effects of greater ω-3 intake.

Is this right? It sounds right that "the reduction in AA-derived eicosanoids" is an explanation for the beneficial effects of omega-3 intake. But it sounds wrong to me that "the diminished activity of the alternative products generated from ω-3 fatty acids" would serve as an explanation. I would expect increased omega-3 intake to produce an increased, not diminished, activity of "the alternative products generated from ω-3 fatty acids". --Coppertwig 01:44, 31 January 2007 (UTC)

I think its correct, but perhaps not as clear as it could be - here is an alternate version:
The reduced concentration of ω-6 derived eicosanoids due to the increased concentration of ω-3 derived eicosanoids serve as one explanation of some of the beneficial effects of greater dietary ω-3 intake.
I believe is less ambiguous as the concentration of n6 eicosanoids has been altered, but their activity per se has not. István 17:55, 1 February 2007 (UTC)
Sorry I didn't reply earlier. Yes, this sentence is much better.

Looking at the changes for the last day in this section, I'm concerned that it's become much more tentative.

yesterday: Increasing dietary ω-3 fat restricts AA-derived eicosanoids. The alternative products—generated from EPA—have comparatively lower activity. These changes serve as the foundation for explaining the beneficial effects of greater ω-3 intake.
today: Increasing dietary intake of ω-3 fatty acids restricts production of AA-derived eicosanoids; the two metabolic pathways utilise, i.e. compete for, the same enzymes. The reduced concentration of AA-derived eicosanoids due to the increased concentration of ω-3 derived eicosanoids serve as one explanation of some of the beneficial effects of greater dietary ω-3 intake.

This is wordier and weaker in places. Common usage is 'omega-3 fats', not 'omega-3 fatty acids' and in the diet, people aren't eating fatty acids, they're eating fat. The eicosanoids aren't just one explanation of some of the beneficial effects; they're the foundation

I used 'EPA-derived' rather than 'ω-3' in this case. I've mentioned in the article that DGLA-derived ω-6 eicosanoids are also anti-inflamatory.

I think 'serve as the foundation' is stronger, and justified by the references. David.Throop 19:58, 1 February 2007 (UTC)

Perhaps there are three points of discussion:

  1. ω-3 v EPA
  2. fats v fatty acids
  3. "one explanation for..." v "the foundation of..."

1) ω-3 is more popularly recognised than is EPA which is another TLA (and there is a minor pathway of DHA>EPA back-conversion). 2) I agree with you as per your above statement, "fats" is better than "fatty acids" (and technically more correct in a dietary sense) and 3) I think its not really known for sure yet. We think its so, and I agree that current literature indicates this, but so much in the techincal literature has changed so quickly (and we still dont fully understand the mechanisms involved) that a qualified statement may be more accurate than a certain one - your call. István 20:32, 1 February 2007 (UTC)

1)ω-3 will be easier for people to recognize; that doesn't mean other things can't also be mentioned. The other things can be referred to by phrases like "longer-chain fatty acids" or "EPA (from fish in the diet, for example)" to make them more understandable to non-experts. 2) I suppose it's probably better to say "omega-3 fats" rather than "fatty acids" when talking about the diet, though I think of the fatty acids, not the fats as being the essential nutrients; 3) I agree with David that "serve as the foundation of" sounds good. I don't think it's overstated given that there is both theoretical understanding of the mechanisms and observational evidence of effects. The next paragraph with its A-level evidence etc. makes the level of evidence clear.

[edit] Intro on pro-inflammatory eicosanoids

In the introduction it says The ω-6 eicosanoids are generally pro-inflammatory; ω-3's are much less so. This introduction could give people the erroneous impression that if they want to reduce inflammation, they should stay away from both omega-3 and omega-6 fats in their diet. I think this needs to be changed, since some people will read only the introduction. It would be better to say:

The ω-6 eicosanoids are generally pro-inflammatory; ω-3's tend to counter them. Or it can say "compete with" or "can soften their effects" or something rather than "counter". --Coppertwig 16:28, 5 February 2007 (UTC)

You make a good point, but this is tricky. This is an area where it's hard to be both correct and not misleading. We have to distinguish between the activities of the ω-3 fats and the eicosanoids derived from them.
  • The prostacyclins in general are anti-inflammatory.
  • The thromboxanes are pro-inflammatory. TXA3 (from EPA) by itself induces inflammation, but weakly. It may be anti-inflammatory in the presence of TXA2. That is, TXA3's activity signalling inflammation may be less than its activity (competitive inhibition) blocking TXA2. But I'm not sure about that and I don't have a cite.
  • LTB5 actually does counteract LTB4; and I've got a good cite for that. I believe the cysteinyl LTs from EPA are still pro-inflammatory, though.
See, much of the anti-inflammatory effect of EPA happens before any eicosanoids get generated at all—by inhibiting the formation of AA-derived eicosanoids. There are some cases where the EPA-derived eicosanoids are anti-inflammatory, but not enough to make a generalized statement. And while EPA is anti-inflammatory, it's not a statement that goes in the introduction, because this is an article about eicosanoids, not about fish oil.David.Throop 17:47, 5 February 2007 (UTC)

[edit] Quoting on eicosanoids and omega-3

Look at how I reformatted your numbered list.  :-) More detail here.

When I wrote this whole paragraph, it was more or less a direct quote from Fritsche. Maybe I should just quote him directly. There's a quotation template that I'm looking around for... 01:01, 2 February 2007 (UTC)

[edit] reader level

Some readers' eyes will glaze over when they come to the "Biosynthesis of leukotrienes", if not earlier. I don't suggest deleting any material. However, it might be helpful to put more accessible information (such as that omega-3 helps reduce inflammation -- the function and pharmacology section) earlier in the article than this challenging paragraph. Another alternative is to possibly convert the "Biosynthesis of leukotrienes" into a figure or table rather than a symbol-filled paragraph. Maybe it's OK to just leave it the way it is and hope some readers will skip the paragraph rather than throwing in the towel. --Coppertwig 02:18, 2 February 2007 (UTC)

Istvan also suggested moving the Biosynthesis material. The problem is that some of the biosynthesis ideas are prerequisite for understanding the health effects and why the pharmacology works. You can't understand how aspirin works until you at least partially understand the COX pathway. I can't explain how and why the omega-3's work—competing for the desaturases, elongases, phospholipases and COX or 5-LO—until I've introduced some of the biosynthesis.

Istvan's suggestion of having a brief overview of Biosynthesis, and moving the more difficult material into a subarticle, seems right. But I think it still has to logically proceed the function, pharmacology and effects.David.Throop 04:12, 2 February 2007 (UTC)

To me, the section "The ω-3 and ω-6 series" is readable and does not require "Biosynthesis of leukotrienes" as a prerequisite. Readers can understand that different pathways compete for enzymes even if they haven't previously been introduced to the specific reactions. Here are some additional editing alternatives to consider:
  • Have a simpler version of "Biosynthesis of leukotrienes", then the function and pharmacology section, then a "Detailed biosynthesis of leukotrienes" with all the technical information. Mentioning "see detailed ... below" can help guide the readers who are interested in more detailed information to refer to that part before reading the rest.
  • Keep "Biosynthesis of leukotrienes" where it is but add more plain English words to it to give the reader a rest. For example, the sentence beginning "The cell must realize some benefit..." could perhaps be moved into the interior of this paragraph. Other sentences such as "A phospholipases is an enzyme which frees a fatty acid off from a fat molecule" or "It only takes a ten-thousandth of a second for a substance to diffuse across the distance from the cell membrane to the cell nucleus" (if that's accurate) could possibly be added, or just some additional words such as inserting "the enzyme" or "the leukotriene" etc. before some symbols, and inserting more words like "although", "and then" etc. I could do some (more) stuff like this but will wait to see what you think.
  • Combine the biosynthesis section with the following sections for which you feel it's a prerequisite. I.e. whenever the reader needs to know a certain fact, state the fact at that time.
  • As I suggested above, make it into a table or figure. --Coppertwig 20:32, 3 February 2007 (UTC)

[edit] Connect the dots in "function and pharmacology"

In the first paragraph:

Eicosanoids have a short half-life, ranging from seconds to minutes. Dietary antioxidants inhibit the generation of some inflammatory eicosanoids, e.g. trans-resveratrol against thromboxane and some leukotrienes.[1] Most eicosanoid receptors are members of the G protein-coupled receptor superfamily; see the Receptors table.

I suggest adding at least one or two sentences between the first and second sentence and at least another one or two between the second and third, if appropriate information can be found, splitting into more than one paragraph if necessary. This would serve two purposes: first, to make this part longer than the corresponding part of the introduction which should logically be a mere summary of it; secondly, to guide the reader in the flow of ideas from one of these sentences to the next. Each of these sentences seems to me to be a sufficiently different topic from each other than perhaps each should be in a separate paragraph, with some other information added to fill out the paragraphs. --Coppertwig 13:41, 2 February 2007 (UTC)

yeah, I know. Right now, the paragraph is just a catch-all for snippets of text that I didn't know what to do with. For right now I'm going to leave it alone. Once we've reworked the Biosynthesis material, it will be clearer what needs to be covered here.

But feel free to take a swipe at it. You (or anybody else tuning in) might try reading Simopoulos and see if you could summarize what he says.

Alternatively, edit Talk:Eicosanoid/to_do. Make a list of what points should be made in the sub-section and I'll try to come up with the text. David.Throop 16:07, 2 February 2007 (UTC)

[edit] Nomenclature

After Its two letter abbreviation I suggest putting "as given above". Also, "PGI" is three letters, so maybe it should say "Its two (or sometimes three) letter abbreviation, as given above."

I just figured out that "An ABC sequence-letter" means a single letter. I had misread it as meaning a sequence of three letters. I think "A single letter" or "one letter" or "one uppercase letter" would be more clear instead. It's not clear what functional groups are referred to. For example, there is more than one functional group beginning with the letter H. When giving examples of eicosanoids at the end of the nomenclature section, I think it would be helpful to spell out the full name of at least one or perhaps all of them:

  • The EPA-derived prostanoids have three double bonds, (e.g. PGG3, PGH3, PGI3, TXA3) while its leukotrienes have five, (LTB5). It would be good to explain here that PGG3 means "a prostaglandin with (oh-oh, I don't see any functional group beginning with the letter G) and with 3 double bonds" and also spell out at least the H, I and A in PGH3, PGI3 and TXA3.

Alternatively, when the ABC sequence-letter idea is mentioned, examples of some functional groups can be given: "e.g. H for hydroxyl, A for aldehyde, ..." or whatever they actually are. --Coppertwig 23:36, 5 February 2007 (UTC)

Thanks for pointing out what is unclear; I've been so close to this stuff for so long that I take a lot for granted.
The A-B-C letters don't stand for anything; they just indicate (roughly) what order the compounds were named. I spelled this out more clearly in the text, but what had been a simple bullet point was getting very long indeed. So I shoved it down into a footnote (you are reading the footnotes, aren't you?) See if this wording is more accessible. Oh, and do follow the link to the Cyberlipid page; it's good. David.Throop 04:55, 6 February 2007 (UTC)