Mead acid (a polyunsaturated fatty acid)

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overkees
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Mead acid (a polyunsaturated fatty acid)

Post by overkees »

If people are 'deficient' of the PUFAs, the body will eventually make large amounts of mead acid (up to 1300 percent more). Because the desaturase enzymes aren't getting inhibited by the PUFAS (yes, PUFAs inhibit desaturase enzymes). Can't this omega-9 fatty acid fulfill this task the omega3/omega6s normally fulfill?
http://link.springer.com/article/10.1007%2FBF02522978 wrote: n-9 Eicosatrienoic acid (ETrA), also known as Mead acid, is a minor fatty acid in essential fatty acid (EFA)-sufficient healthy subjects but is found at increased levels in EFA deficiency. This study examined the influence of dietary ETrA from a biological source on plasma and tissue ETrA. The incorporation was reduced in diets with higher LA content compared to diets containing similar amounts of ETrA but lower LA. All rats remained apparently healthy, and histological survey of major organs revealed no abnormality. While the long-term implications for health of ingestion of diets rich in ETrA remain to be established, rats appear to tolerate high levels of dietary ETrA without adverse effects. Dietary enrichment with ETrA warrants further investigation for possible beneficial effects in models of inflammation and autoimmunity, as well as in other conditions in which mediators derived from n-6 fatty acids can affect homeostasis adversely.
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Re: Poly-unsaturated fatty acids & Lipid peroxidation

Post by RRM »

mead acid . ... Can't this omega-9 fatty acid fulfill this task the omega3/omega6s normally fulfill?
Probably not, as various PUFAs have so many different functions, probably many still unknown.
If mead acid is as good as all the other PUFAs, why doesnt the body produce more mead acid when other PUFAs are not deficient?
Why do PUFAs inhibit the desaturase enzymes that are required for making mead acid from sugars/fats?
So, the body obviously prefers the other PUFAs, when available.

And: mead acid is a polyunsaturated fatty acid as well, susceptible to lipidoxidation, so whats the point?
The issue still remains: do humans benefit from PUFAs, or not.
The evidence in favor for PUFAs is overwhelming.
overkees
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Re: Poly-unsaturated fatty acids & Lipid peroxidation

Post by overkees »

Mead acid has very interesting properties in relation to the other PUFAs:
In summary, the anti-inflammatory effect of EFA deficiency was more marked that that of dietary (n-3) fatty acid supplementation in acute inflammation

The results establish that dietary ETrA effectively inhibits synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA).

These results suggest that the dietary supplementation of ETrA may have both prophylactic and therapeutic effects on experimentally produced bowel lesions. Further investigations are necessary to clarify the effects of ETrA on bowel lesions and its mechanisms.

This pattern indicates inhibition of LTA synthase in EPA-fed rats. The results establish that dietary ETrA effectively inhibits synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA).

http://link.springer.com/article/10.1007%2FBF02522978
http://www.ncbi.nlm.nih.gov/pubmed/8648425
http://www.ncbi.nlm.nih.gov/pubmed/8245797
http://www.ncbi.nlm.nih.gov/pubmed/12884098
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

"Scientists have induced EFA deficiency in animals by feeding them fully hydrogenated coconut oil as their only fat. (Full hydrogenation gets rid of all the EFAs; coconut oil is used because it is the only fat that can be fully hydrogenated and still be soft enough to eat.) The animals developed dry coats and skin and slowly declined in health, dying prematurely."

Mead acid is converted by COX to PG-s1, TX-s1, LT-s3.
EPA is converted by COX to PG-s3, PGG3, PGH3.
AA is converted by COX to PG-s2, PGG2, PGH2.

Work in progress..
1. Dietary mead acid may confer the same anti-inflammatory benefits of EFAD (essenltial fatty acid defuriciency) or dietary fish oil. Mead acid may have an advantage above fish oil as it is less unsaturated.
2. Reduction of omega 6 and accumulation of mead acid may be important for maintaining normal cartilage structure.
3. Dietary mead acid may have therapeutic effects for bowel lesions.
4. Dietary mead acid reduces LTB4 synthesis by LTA hydrolase inhibition. And dietary LA lowers cellular mead acid in rats.
5. EPA exhibits beneficial effects, whereas mead acid showed an opposite effect on some tumour parameters.
6. Cartilage contains high levels of mead acid but no blood vessels. Mead acid might inhibit angiogenesis.

1.This pattern indicates inhibition of LTA synthase in EPA-fed rats. The results establish that dietary ETtA effectively inhibits synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA). Because ETrA is substantially less unsaturated than EPA, it can be expected to have greater chemical stability, which could be an important practical advantage when used as a dietary constituent or supplement.

2. Previously, EFA deficiency has been shown to greatly suppress the inflammatory response of leukocytes and rejection of tissues transplanted into allogeneic recipients. Because eicosanoids, which are derived from EFA, have been implicated in the inflammatory responses associated with arthritic disease, reduction of n-6 PUFA and accumulation of the n-9 20:3 acid in cartilage may be important for maintaining normal cartilage structure.
http://www.fasebj.org/content/5/3/344.short

3. "the effect of an ETrA-enriched diet on experimental bowel lesions was examined in this study.
rats were freely fed either an ETrA-enriched or a standard diet. After 7 days of feeding, acute bowel lesions were induced
the rats fed an ETrA-enriched diet showed increased levels of ETrA in the plasma and intestinal mucosa, and a decreased inflammation score.
However, there was no significant decrease in plasma and intestinal mucosal LTB4 in the ETrA-enriched diet-fed rats.
http://link.springer.com/article/10.100 ... -9?LI=true

"Eicosatrienoic acid (ETrA) is the (n-9) homologue of (n-6) arachidonic acid (AA) and (n-3) eicosapentaenoic acid (EPA). ETrA can be synthesized endogeneously, but tissue levels are normally undetectable except in essential fatty acid (EFA) deficiency.
Dietary ETrA was efficiently incorporated into phospholipids with no evident saturation with levels up to 10 mol/100 mol total fatty acids
ETrA levels were lower in rats fed the higher level of LA.
ETrA accumulation correlated with reduced LTB4 synthesis (by LTA hydrolase inhibition) / suppressed inflammatory eicosanoid synthesis
http://europepmc.org/abstract/MED/86484 ... V5MKU6i.24

"The essential fatty acid deficiency (EFAD) is related to cancer development.
EPA showed an anti-proliferative effect on human tumour cell lines.
ETA: lipid peroxidation was decreased, whereas cell proliferation was increased.
EFA (20:5 n-3) exhibited beneficial effects, whereas unusual ETA showed an opposite effect
http://www.ncbi.nlm.nih.gov/pubmed/14518560

"Eicosatrienoic acid (ETA 5,8,11, n-9) is abnormally increased by essential fatty acid deficiency (EFAD), a condition associated with alterations of cell proliferation and differentiation.
Mead's acid) is a down regulator of antimetastatic E-cadherin and desmoglein expression."
http://www.plefa.com/article/S0952-3278 ... 9/abstract


"Addition of 20:3n-9 and n-3 eicosatrienoic acid (20:3n-3) inhibited VEGF-A-stimulated angiogenesis
Arachidonic, eicosapentaenoic, dihomo-γ-linolenic (20:3n-6) and oleic acids did not affect VEGF-A-stimulated angiogenesis
Arachidonic and dihomo-γ-linolenic acids enhanced angiogenesis without VEGF-A.
20:3n-9 in cartilage may be related to its vessel-free status and 20:3n-9 may be useful for the treatment of disorders with excessive vasculature."

"dietary n-3 polyunsaturated fatty acids antagonise AA metabolism.
Dietary eicosatrienoic acid (20:3n-9, ETrA) also antagonizes arachidonic acid (AA) metabolism, but differently
http://www.ncbi.nlm.nih.gov/pubmed/11534547

"In cases of essential fatty acid deficiency, Mead acid (20:3n-9) is synthesized from oleic acid.
levels were markedly higher in human fetal cartilage than in the muscle, liver and spleen.
osteoblastic activity was again significantly decreased with 20:3n-9 (10–30 μM) after 6-h incubation but not after 18 h incubation.
The presence of 20:3n-9 in fetal cartilage may be important for the prevention of calcification in the cartilage."
http://www.plefa.com/article/S0952-3278 ... 2/abstract

"When rats adapted to a fat-free diet were fed a corn oil diet, endogenous ETA was quickly substituted by AA
under a fish oil diet, ETA was quickly substituted by EPA and DHA
In both cases the ETA almost disappeared in 6 days.
when the dietary process was reversed, AA decreased more slowly than the n-3
In platelets, even in LA-deficient rats, much AA remained, though decreasing similarly to the n-3 in the plasma.
http://europepmc.org/abstract/MED/6424720

"Oleic acid did not form lipid peroxides and this fatty acid stimulated cell proliferation.
All fatty acids which generated lipid peroxides inhibited cell proliferation, only correlated with the degree of lipid peroxidation in the n-9 fatty acid family.
AA and DHA inhibited prostaglandin biosynthesis.
18∶2(n-6), 18∶2(n-9), 18∶3(n-3), 20∶2(n-9), 20∶3(n-3) and 20∶5(n-3) had no effect on prostaglandin biosynthesis.
18∶3(n-6), 20∶3(n-6) and 20∶4(n-6) generated prostaglandins.
Mead acid generated metabolites with prostaglandin immunoreactivity and the most effective inhibitors of cell proliferation
http://link.springer.com/article/10.100 ... 84?LI=true

"Unsaturated fatty acids present in the lipids of essential fatty acid (EFA)-deficient rats
high levels of these acids cannot account fully for the reported loss of prostaglandin synthetic capacity of these EFA-deficient animals.
http://www.sciencedirect.com/science/ar ... 8074900501
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

Mead acid production is not a reliable indicator of EFA status, as the mead acid/AA ratio is also up regulated in protein energy malnutrition.

"malnourished children showed a marked decrease of polyunsaturated FA with low LA ... severely reduced linoleic acid metabolites, incl. AA.
and a reduction of DPA and DHA ... increased values for saturated FA and non-essential monoenoic FA
no significant difference between marasmus and kwashiorkor.
in the early phase of recovery during hospital treatment ... LA had increased, but not metabolites
may be due to low insulin levels, protein and zinc deficiency."
http://www.ncbi.nlm.nih.gov/pubmed/3089792

Biochemical evidence of essential fatty acid deficiency (EFAD) may exist in
Some protein-energy malnutrition (PEM), notably skin changes, impaired resistance to infections, impaired growth rate and disturbed development
may at least partly be explained by essential fatty acid deficiency (EFAD)
PEM may induce EFAD, due to low EFA intake, poor lipid digestion, absorption, transport, desaturation and increased EFA beta-oxidation and peroxidation.
EFAD may perpetuate itself by decreasing lipid absorption and transport, and aggravate PEM by impairing nutrient absorption and dietary calorie utilisation. M
http://www.ncbi.nlm.nih.gov/pubmed/1530 ... t=Abstract
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

As far as I've read mead acid is potentially something very useful in some inflammation diseases.
It inhibits LTB4 synthesis, and this is really useful in many chronic diseases.

" Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation"
"LTB4-mediated attraction of neutrophils to skin subjected to tape stripping, a surrogate for scratching, is essential for development of allergic inflammation. "
"Drugs that block the actions of LTB4 have shown some efficacy in slowing the progression of neutrophil-mediated diseases."
"LTs are clearly involved in airway inflammation and certain clinical features of asthma. Evolving evidence indicates that LTB4 has an important role in the development of asthma, and that CysLTs are key mediators of the airway remodeling process."
"The concentrations of LTB4 in joint tissue of arthritic mice and nonarthritic control mice were determined. Levels of LTB4 were significantly elevated in the joint tissues of mice with chronic arthritis. No leukotrienes were detected in the joint tissues of mice without arthritis."
"The mice receiving the 5-LO inhibitor did not develop arthritis."
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Re: Mead acid (a polyunsaturated fatty acid)

Post by overkees »

Article about the basics of PUFA metabolism of omega3s and omega 6s that I edited by making it shorter. We might work with this to compare the mead acid metabolites and properties:
http://www.pensgard.com/nutrition/4_Prostaglandins.htm

About eicosanoids:

Prostaglandins are a subset of a larger family of substances called eicosanoids. Other subgroups include thromboxanes, leukotrienes and lipoxins. Eicosanoids are localized tissue hormones that seem to be the fundamental regulating molecules in most forms of life. They do not travel in the blood like hormones, but are created in the cells to serve as catalysts for a large number of processes including the movement of calcium and other substances into and out of cells, dilation and contraction, inhibition and promotion of clotting, regulation of secretions including digestive juices and hormones, and control of fertility, cell division and growth.

The omega-6 pathway begins with linoleic acid (LA). It is desaturated by delta-6 desaturase (D6D), resulting in gamma-linolenic acid, GLA. An elongase enzyme adds two carbon atoms and you will get dihomo-gamma-linolenic acid (DGLA).
DGLA forms the root of the Series 1 prostaglandins such as PGE1, PGF1a, and PGD1, and thromboxanes such as TXA1

DGLA is then transformed into arachidonic acid (AA).
AA is the root or precursor of the Series 2 eicosanoids. The family includes pge2 pgf2a and pgd2 prostacyclins such as pgI2, thromboxanes such as TXA2, leukotrienes and lipoxins.

Series 3 prostaglandins begins with alpha-linolenic acid (ALA). ALA is desaturated twice and elongated once to produce eicosapentaenoic acid (EPA).
EPA is the root substance of the Series 3 family that includes the prostaglandins such as PGE3, PGH3 and PGI3, thromboxanes such as TXA3 and leukotrienes. EPA is then further elongated and desaturated to produce docosahexaeonic acid (DHA) a 22-carbon fatty acid with six double bonds.

The Series 2 group is involved in intense actions, often in response to some emergency such as injury or stress (If the rate of synthesis is too fast, excess active eicosanoids can cause pathophysiology(1)); the Series 3 group has a modulating effect. The Series 3 prostaglandins are formed at a slower rate and work to attenuate excessive Series 2 production.

Series 2 prostaglandins seem to be involved in swelling, inflammation, clotting and dilation, while those of the Series 1 group have the opposite effect. Series 2 prostaglandins also seem to play a role in inducing birth, in regulating temperature, in lowering blood pressure, and in the regulation of platelet aggregation and clotting.

About desaturases

One of the most common blocks in the prostaglandin chain involves delta-6 desaturase (D6D). When action of this enzyme is blocked, so is the entire pathway. This vital enzyme is inhibited first and foremost by trans fatty acids found in margarine, shortening and hydrogenated fats.(2) In addition, excess of EFA's, especially omega-6 EFA's, can cause problems with both pathways. This is because both pathways begin with desaturation by the same delta-6 desaturase enzymes. So too much omega-6 in the diet also "uses up" the delta-6 desaturase enzymes needed for the omega-3 pathway 2

Deficiencies of biotin, vitamin E, protein, zinc, B12 and B6 all interfere with the action of delta-6 desaturase and other enzymes involved in prostaglandin production. 2. Alcohol consumption interferes with D6D, as does malnutrition and overeating--so moderation is the key to tripping lightly down the prostaglandin pathway. An excess of oleic acid (found chiefly in olive oil and nuts) may inhibit prostaglandin production. [Horrobin, David F, Prostaglandins: Physiology, Pharmacology and Clinical Significance The Book Press, Brattleboro, Vermont, 1978, p 20, 35]

Diabetes, poor pituitary function and low thyroid function are synonymous with altered and inhibited D6D function. 2

Lauric acid, a 12-carbon saturated fatty acid found chiefly in mother's milk and coconut oil, and in smaller amounts in butter, seems to improve the function of the omega-6 pathway. 2When lauric acid is present in the diet, the long chain omega-6 fatty acids accumulate in the tissues where they belong, even when consumption of essential fatty acids is low.

The actions of delta-5 and delta-4 desaturase enzymes further along the pathway are less well understood, because they have not been as well studied. Nevertheless, it is known that diabetes, protein deficiency and alcohol all inhibit the action of D5D.

The desaturase enzyme systems do not work well in infants. This is why mammalian milk is rich in long chain fatty acids of both pathways--AA, EPA and DHA.

The desaturase enzyme systems also become less efficient in old age.

Carnivorous animals lack both D6D and D5D enzymes, and must obtain the longer chain fatty acids from their food supply. Some population groups that have been largely carnivorous for generations, such as the Eskimo and Irish seacoast peoples, also lack these enzymes.

Effect of drugs/medicines:

Aspirin and steroids inhibit TXA2 activity and therefore reduce swelling; Lithium inhibits PGE1 which seems to be elevated in manic-depressive disorders.
Melatonin, amantadine and colchicine (used to treat gout) activate TXA2 .
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

Carnivorous animals lack both D6D and D5D enzymes, and must obtain the longer chain fatty acids from their food supply. Some population groups that have been largely carnivorous for generations, such as the Eskimo and Irish seacoast peoples, also lack these enzymes.
So this means that Esimo's, Irish seacoast people, and carnivorous animals cannot make DGLA, AA, EPA or mead acid, right ?

Edit: For some reason Eskimo's may be able to make DGLA (although they haven't got desaturase-6):
"The low prevalences of CHD, psoriasis, asthma and rheumatoid arthritis in Eskimos have been attribute to the high dietary intake of EPA from fish and marine mammals. However, even on a Western diet, Eskimos have plasma arachidonic acid (AA) levels far below those seen in Europeans while dihomogammalinolenic acid (DGLA) levels are higher in Eskimos. These low AA and high DGLA levels seem to be due to a genetic abnormality in EFA desaturation since they are found even when EPA intakes are low. Since AA is known to be important in the pathogenesis of CHD, asthma, psoriasis and arthritis, while DGLA has properties which make it of likely therapeutic value in these conditions, the genetically high DGLA and low AA are likely to be as important as dietary EPA in determining Eskimo disease patterns."
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Re: Mead acid (a polyunsaturated fatty acid)

Post by overkees »

Well I suppose they have the elongase enzymes, so they can make the DGLA from dietary GLA. I don't know anything about dietary GLA, though.
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

I thought that only borage oil, primose oil and hemp oil have significant amounts of GLA. I don't think eskimo's consume those.

Yesterday I was thinking, if you get sufficient amount of EPA and AA by diet (by eating fish and egg yolks for example), then why would you want delta-5 desaturase. If you eat such a diet, D5D will only give problems (by overproducing AA for example).
That eskimo's lack D5D (and D6D) shows that nature things the exact same thing. If your diet is sufficient in EPA and AA, it seems evolutionary better to have no D5D.
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Re: Mead acid (a polyunsaturated fatty acid)

Post by overkees »

Well an eskimo diet is not exactly the thing you would want.. excessive bleeding issues and such if I recall correctly. 7
http://www.ncbi.nlm.nih.gov/pubmed/7438807
The bleeding tendency in Greenland Eskimos "Related to this decreased morbidity is the greater bleeding tendency among Greenland Eskimos, summarized by Bang and Dyerberg (1980)."

http://www.ncbi.nlm.nih.gov/pubmed/7457208
Epidemiological studies in the Upernavik district, Greenland. Incidence of some chronic diseases 1950-1974. "The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis."

http://www.ncbi.nlm.nih.gov/pubmed/18457208 "In 1991, life expectancy at birth in the Inuit-inhabited areas was about 68 years, which was 10 years lower than for Canada overall. From 1991 to 2001, life expectancy in the Inuit-inhabited areas did not increase, although it rose by about two years for Canada as a whole."
Of course the body wants to block the desaturases if PUFAs are high. But I think that in nature food is often scarce, therefore we often had not enough food, and we might have therefore relied on the mead acid. I don't think consumption of nuts and seeds have formed a big part in our diets. Neither did fatty fish.

I think you can better rely on a minimum for a short while, then the body will do everything it can to preserve its existence. Rather than make it lazy by never giving it the need to push itself into adapting to better efficiency. That is a reason why I'm a big fan of fasting every once a while. I feel much more efficient now when I don't fast. I can also go smoothly into a fasting state, no headaches, no nothing.

By giving short lasting high stress signals, the body will improve itself to get better. If you have chronic high stress it will get exhausted and can't overcome the stress anymore.
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Re: Mead acid (a polyunsaturated fatty acid)

Post by RRM »

Kasper wrote:I thought that only borage oil, primose oil and hemp oil have significant amounts of GLA. I don't think eskimo's consume those.
Fish also contain GLA, such as salmon.
overkees wrote:Of course the body wants to block the desaturases if PUFAs are high. But I think that in nature food is often scarce, therefore we often had not enough food, and we might have therefore relied on the mead acid. I don't think consumption of nuts and seeds have formed a big part in our diets. Neither did fatty fish.
Its not just fish and nuts, but also any kind of meat and eggs.
And fruits also contain LNA... http://www.waiworld.com/waidiet/nut-omega3.html
Its not likely we would not get enough PUFA from a raw food diet if it supplied us with enough energy.
You would have to consume very specific foods only.
By giving short lasting high stress signals, the body will improve itself to get better.
And you know what molecules are involved in such high stress signals?
Products from PUFAs such as DHA products, as in enzymatic lipid peroxidation.
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Re: Mead acid (a polyunsaturated fatty acid)

Post by Kasper »

Mead acids is converted by COX to 13-hydroxy-5,8,11-icosatrienoate (the major product), 11-hydroxy-5,8,12-icosatrienoate, 9-hydroxy-5,7,11-icosatrienoate, and two isomeric 8,11-dihydroxy-5,9,12-icosatrienoates. No prostaglandin-like, cyclized products could be identified. http://www.ncbi.nlm.nih.gov/pubmed/3084488

Mead acid (ETrE) is converted to 5-HETrE and 5-oxoETrE by neutrophills.

I don't know if those metabolites have any beneficial effects.

The beneficial effects of mead acids may come from it's ability to inhibit LBT4 synthesis by LTA hyydrolase inhibition.
Mead is readily converted to LTA3 (via the 5-lipoxygenase-leukotriene pathway) (Source: J Biol Chem. 1983 Nov 10;258(21):12797-800)
LTA3 is known to inhibit LTA hydrolase. Therefore LTA3 is not converted to significant amounts of LTB3.
AA is converted by LO-5 to LTA4, and LTA4 is converted by LTA hydrolase to LTB4.

DGLA and EPA are also able to inhibit LTB4 production
"When released from membranes, DGLA may act directly as an inhibitor of 5-LO. DGLA decreased leukotriene LTB4 production by human mononuclear leukocytes in vitro in a dose-dependent manner (28). Alternatively, DGLA can be further oxidized to produce a more potent 5-LO inhibitor. DGLA is not a substrate for 5-LO, but instead is converted by 15-LO to 15-OH-DGLA (aka 15-HETrE). 15-HETrE blocks conversion of AA to LTA4 by direct inhibition of 5-LO (29) and is a stronger inhibitor of LTB4 production than is DGLA (50x).
...
Finally, in contrast to DGLA, EPA is a substrate for 5-LO, and thus competes with AA for the enzyme’s active sites (35). Not only are the total amounts of 4-series leukotrienes reduced, but the kinetics of production are slowed (35). 5-series leukotrienes are produced from the action of 5-LO on EPA, but these have much reduced bronchoconstricting activity compared to LTC4, LTD4 and LTE4 (38)."
http://efficas.com/Content/HCP/Efficacy/Mechanism.aspx
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Re: Mead acid (a polyunsaturated fatty acid)

Post by overkees »

Kasper wrote:Mead acid (ETrE) is converted to 5-HETrE and 5-oxoETrE by neutrophills.

I don't know if those metabolites have any beneficial effects.
I think everything has (or could have) beneficial effects, the only question is to what extent and till what dose?

The only thing I know is that 5 OXO - ETrE is able to imitate the AA metabolites when it comes to optimal 5 OXO receptor activity.

http://www.ncbi.nlm.nih.gov/pubmed/21334434
The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family. neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE.
The main Mead acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B3. We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty acid deficiency.

Kasper wrote: Mead acids is converted by COX to 13-hydroxy-5,8,11-icosatrienoate (the major product), 11-hydroxy-5,8,12-icosatrienoate, 9-hydroxy-5,7,11-icosatrienoate, and two isomeric 8,11-dihydroxy-5,9,12-icosatrienoates. No prostaglandin-like, cyclized products could be identified. http://www.ncbi.nlm.nih.gov/pubmed/3084488
I did find this: Lagarde M et al. E2-like activity of 20:3n-9 platelet lipoxygenase end-product.
"At low concentrations (below 5 X 10(-7) M) it potentiated aggregation but inhibited it at higher levels, a pattern similar to that obtained with prostaglandin E2. "

EPA compared to mead acid:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191266/
"The incorporation of dietary ETrA into rat neutrophils and its effect on A23187-stimulated 5-lipoxygenase metabolism in these cells was examined; in addition, the effect of ETrA was compared with that of EPA, which is known to accumulate in cell membranes and inhibit synthesis of leukotriene B4 (LTB4) a product of the 5-lipoxygenase metabolic pathway. Rats were fed a defined diet that was sufficient in essential fatty acids and that contained EPA or ETrA (0.014% of energy) or no added fatty acid, for 3 wk. In the cells from ETrA-fed rats, LTB4 synthesis was inhibited relative to control values, but synthesis of the other products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and the all-trans isomers of LTB4, were not inhibited"
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Re: Mead acid (a polyunsaturated fatty acid)

Post by overkees »

Also very interesting:
Oxygenation of 5,8,11-eicosatrienoic acid by prostaglandin H synthase-2 of ovine placental cotyledons: isolation of 13-hydroxy-5,8,11-eicosatrienoic and 11-hydroxy-5,8,12-eicosatrienoic acids.

http://www.ncbi.nlm.nih.gov/pubmed/9106061
Prostaglandin H synthase-1 of ram vesicular glands metabolises 5,8,11-eicosatrienoic (Mead) acid to 13R-hydroxy-5,8,11-eicosatrienoic and to 11R-hydroxy-5,8,12-eicosatrienoic in a 5:1 ratio. We wanted to determine the metabolism of this fatty acid by prostaglandin H synthase-2. Western blot showed that microsomes of sheep and rabbit placental cotyledons contained prostaglandin H synthase-2, while prostaglandin H synthase-1 could not be detected. Microsomes of sheep cotyledons metabolised [1-14C]5,8,11-eicosatrienoic acid to many polar metabolites and diclofenac (0.05 mM) inhibited the biosynthesis. The two major metabolites were identified as 13-hydroxy-5,8,11-eicosatrienoic and 11-hydroxy-5,8,12-eicosatrienoic acids. They were formed in a ratio of 3:2, which was not changed by aspirin (2 mM).Prostaglandin H synthase-1 and -2 oxygenate 5,8,11-eicosatrienoic acid only slowly compared with arachidonic acid.
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