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Arachidonate
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Research News:
· Arachidonic acid, 20:4n6, n-6 eicosatetraenoic acid, AA, ARA
o Arachidonic acid is the predominant fatty acid in most tissues
(diet-dependent!) acted upon by cyclooxygenase (to form prostaglandins and
thromboxanes) and lipoxygenase (to form leukotrienes); it is the major n-6 in
cell membranes and body tissues
o Liberated from phospholipids by phospholipase enzymes, most notably
phospholipase A2.
o Most end-products of arachidonate metabolism are pro-inflammatory and are “in
general harmful”[1] although arachidonate itself is a necessary component of
phospholipids and sphingolipids in cell membranes.
o Arachidonate and its metabolites are referred to as eicosanoids.[2]
Arachidonic acid is the predominant fatty acid in membrane phospholipids and is
the preferred substrate for eicosanoid production relative to EPA.[3] Given that
arachidonate’s eicosanoids are biologically more powerful than those of EPA, we
can accurately generalize that arachidonate and its respective prostaglandins
and leukotrienes dominate the fatty acid and eicosanoid playground in both
quantitative and qualitative respects. Therefore, successful intervention
against arachidonate metabolism must consider 1) the quantity of arachidonate,
2) the balance of n-3 to n-6, and also 3) specific measures to hinder the
production of the harmful arachidonate metabolites.
o Arachidonic acid is the direct precursor to the isoprostanes 8-iso
prostaglandin-E2 (8-iso-PG-E2) and 8-iso prostaglandin-F2-alpha
(8-iso-PG-F2-alpha), mediators that possess inflammatory and hyperalgesic
properties and which are produced by the radical-mediated non-enzymatic
peroxidation of arachidonate.[4] Inhibition of cyclooxygenase and/or
lipoxygenase does not decrease the inflammatory and pain-producing effects of
isoprostanes. Production of 8-iso-PG-F2-alpha is increased by and is a marker of
oxidative stress. Obviously, inhibition of isoprostane formation is part of the
biochemical and therefore clinical justification for antioxidant therapy in the
treatment of painful orthopedic and rheumatic disorders. Supplemental ascorbic
acid, tocopherols, and EPA have been shown to lower isoprostane levels in
humans.
o Formation of arachidonate from DGLA is inhibited by EPA.[5]
o Formation of arachidonic metabolites is not increased by vitamin C.[6]
o The term “eicosatetraenoic acid” can apply to both 20:4n6 (arachidonic acid)
of the omega-6 fatty acid family[7] and to 20:4n3 of the omega-3 fatty acid
family. [8],[9] Therefore, to avoid the confusion that would result from the use
of the term “eicosatetraenoic acid” by itself, “n-6 eicosatetraenoic acid”
should be used when referring to 20:4n6 (arachidonic acid) and “n-3
eicosatetraenoic acid” should be used when referring to 20:4n3.
o Liberation of arachidonic acid from membrane phospholipids phosphatidylcholine
and phosphatidylinositol is increased by contact with IgE.[10] This finding
presumably helps explain why inflammatory conditions are generally exacerbated
by allergen exposure and why allergy elimination and anti-allergy
immunomodulatory treatments result in a reduction in pain and inflammation.
o Elevated ARA may lead to altered binding of hormones, growth factors,
neurotransmitters, and common food antigen peptides.
o Dietary ARA works synergistically with proinflammatory genotypes such as the
variant 5-lipoxygenase alleles which are common in the general population:
Africans (24%), Asians and Pacific Islanders (19.4%), other racial/ethnic groups
(18.2%), Hispanics (3.6%), whites (3.1%), and the atherogenic effect of dietary
arachidonic acid in these patients can be mitigated by dietary EPA.[11]
--------------------------------------------------------------------------------
[1] Horrobin DF. Ascorbic acid and prostaglandin synthesis. Subcell Biochem.
1996;25:109-15
[2] Delvin TM. Textbook of Biochemistry with Clinical Correlations. New York:
Wiley-Liss, 1997. Pages 431-441
[3] Rubin D, Laposata M. Cellular interactions between n-6 and n-3 fatty acids:
a mass analysis of fatty acid elongation/desaturation, distribution among
complex lipids, and conversion to eicosanoids. J Lipid Res. 1992
Oct;33(10):1431-40
[4] Evans AR, Junger H, Southall MD, Nicol GD, Sorkin LS, Broome JT, Bailey TW,
Vasko MR. Isoprostanes, novel eicosanoids that produce nociception and sensitize
rat sensory neurons. J Pharmacol Exp Ther. 2000 Jun;293(3):912-20
[5] Horrobin DF. Interactions between n-3 and n-6 essential fatty acids (EFAs)
in the regulation of cardiovascular disorders and inflammation. Prostaglandins
Leukot Essent Fatty Acids 1991 Oct;44(2):127-31
[6] Horrobin DF. Ascorbic acid and prostaglandin synthesis. Subcell Biochem.
1996;25:109-15
[7] “5,8,11,14-eicosatetraenoic (20:4(n-6))” Mimouni V, Christiansen EN, Blond
JP, Ulmann L, Poisson JP, Bezard J. Elongation and desaturation of arachidonic
and eicosapentaenoic acids in rat liver. Effect of clofibrate feeding. Biochim
Biophys Acta. 1991 Nov 27;1086(3):349-53
[8] Tapiero H, Ba GN, Couvreur P, Tew KD. Polyunsaturated fatty acids (PUFA) and
eicosanoids in human health and pathologies. Biomed Pharmacother. 2002
Jul;56(5):215-22
[9] Erasmus U. Fats that heal, fats that kill. British Columbia Canada: Alive
Books, 1993 Page 276
[10] McGlivery RW. Biochemistry: A Functional Approach. Third Edition.
Philadelphia: WB Saunders, 1983. Pages 747-750
[11] Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M.
Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and
atherosclerosis. N Engl J Med. 2004 Jan 1;350(1):29-37
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Dr Vasquez's Comments:
This is an excerpt from my textbook "Chiropractic and Naturopathic
Mastery of Common Clinical Disorders" which is available from
OptimalHealthResearch.com
(website with clinical information designed for doctors) and also from
OptimalHealthNutrition.com
in our selection of books.
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