OptimalHealthNutrition.com -- Cyclooxygenase-2 (cox2) is an enzyme that converts arachidonic acid into prostaglandins

COX-2

Research News: Cyclooxygenase (COX) (also called “prostaglandin synthase” or “PGS” or “prostaglandin endoperoxide synthase”)
COX-1 is “constitutive” and is found in all cells, while COX-2 is inducible by stimulation from monocytes/macrophages following stimulation by PAF, IL-1, or bacterial lipopolysaccharide; its induction is inhibited by glucocorticoids.[1]
COX is irreversibly inhibited following acetylation by aspirin.
The expression of COX is inhibited by glucocorticoids,[2] which also inhibit phospholipase A2.
COX forms TXs and PGs, while LIPOX form LTs.
The COX metabolite PG-F2alpha is necessary for the formation of matrix metalloproteinase-2 and other collagenases which are utilized for the destruction of connective tissue[3]
COX is apparently activated by either n-6 fatty acids or the oxidized metabolites of n-6 fatty acids.[4] Therefore, consumption of n-6 fatty acids alone—without trauma or inflammatory stimuli—is sufficient for the increased production of the harmful arachidonate-derived prostaglandins and leukotrienes. Thus, by definition, a diet high in n-6 fatty acids may subtly yet significantly promote pain, inflammation, joint destruction, and cancer.
A well-established consequence of inhibiting COX is that of increasing LIPOX metabolites. Inhibiting COX will decrease COX metabolites, yet will cause an increase in LIPOX metabolites because of increased substrate levels; i.e., the liberated arachidonate that is not metabolized by COX is now available to be metabolized by LIPOX. Thus, inhibiting COX produces a “metabolic shunt” effect that increases production of inflammatory mediators such as HETE and the leukotrienes. Additionally, inhibition of COX inhibits formation of the beneficial anti-inflammatory DGLA metabolites.
Arachidonate metabolites from COX function for the most part to increase inflammation and pain.[5]
Increased expression of COX-2 increases production of PG-E2 and has been associated with increased production of anti-apoptotic proteins and a reduction in pro-apoptotic proteins in cultured rat intestinal cells.[6]
The activity of lipoxygenase and cyclooxygenase produces reactive oxygen species (ROS) intermediates.
The paradox of how a single enzyme such as cyclooxygenase can produce such a wide array of metabolites from a single substrate such as arachidonic acid is solved by recognizing that arachidonate is three-dimensionally rearranged once within the cyclooxygenase enzyme and that these random arrangements favor the production of different metabolites by the preferential molecular modification of the original arachidonate.[7] Additionally, cyclooxygenase may become slightly rearranged as well, thus further promoting the heterogeneity of progeny.

--------------------------------------------------------------------------------

[1] Delvin TM. Textbook of Biochemistry with Clinical Correlations. New York: Wiley-Liss, 1997. Pages 431-441

[2] Tapiero H, Ba GN, Couvreur P, Tew KD. Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed Pharmacother. 2002;56(5):215-22

[3] "Specific metabolites of each pathway, i.e. PGF2 alpha and 5-HPETE, are able to transcend the block and restore collagenase production, invasiveness in vitro and metastatic activity in vivo." Reich R, Martin GR. Identification of arachidonic acid pathways required for the invasive and metastatic activity of malignant tumor cells. Prostaglandins 1996 Jan;51(1):1-17

[4] “ …due to activation of cyclooxygenase either by oxygenated metabolites of n-6 fatty acids or by the n-6 fatty acids themselves.” 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

[5] Tapiero H, Ba GN, Couvreur P, Tew KD. Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed Pharmacother. 2002;56(5):215-22

[6] Tapiero H, Ba GN, Couvreur P, Tew KD. Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed Pharmacother. 2002;56(5):215-22

[7] Thuresson ED, Lakkides KM, Smith WL. Different catalytically competent arrangements of arachidonic acid within the cyclooxygenase active site of prostaglandin endoperoxide H synthase-1 lead to the formation of different oxygenated products. J Biol Chem. 2000 Mar 24;275(12):8501-7 Available on-line at http://www.jbc.org/cgi/reprint/275/12/8501 on March 16, 2004

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.

				OptimalHealthNutrition.com

			Update: Please see the new website at HealGrowThriveMedicine.com