Arachidonic add

Qu W, Bradbury JA, Tsao CC, Maronpot R, Harry GJ, et al. 2001. Cytochrome P450 CYP2J9, a new mouse arachidonic add omega-1 hydroxylase predominantly expressed in brain. J Biol Chem 276 25467-25479. 

The omega (<0) numbering system is also used for unsaturated fatty acids. The co-family describes the position of the last double bond relative to the end of the chain. The omega designation identifies the major precursor fatty add, e.g., arachidonic add is formed from linoleic acid (co-6 family). Arachidonic acid is itself an important precursor for prostaglandins, thromboxanes, and leukotrienes. 

Essential fatty acids are fatty acids that have to be supplied in the diet. Without exception, these are all polyunsaturated fatty acids the C20 fatty acid arachidonic add (20 4 5,8,11,14) and the two Cis acids linoleic add (18 2 9,12) and linolenic add (18 3 9,12,15). The animal organism requires arachidonic acid to synthesize eicosanoids... 

The eicosanoids are a group of signaling substances that arise from the C-20 fatty acid arachidonic add and therefore usually contain 20 C atoms (Greek eicosa = 20). As mediators, they influence a large number of physiological processes (see below). Eicosanoid metabolism is therefore an important drug target. As short-lived substances, eicosanoids only act in the vicinity of their site of synthesis (paracrine effect see p.372). 

Muller G, Ayoub M, Stoiz P, Rennecke ], Fabbro D, Pfizenmaier K (1995) PKC zeta is a molecular switch in signal transduction of TNF-alpha, bifimctionally regulated by ceramide and arachidonic add. EMBO J 14 1961-1969... 

Fig. 6.11. Formation and function of diacylglycerol. The figure schematically shows two main pathways for formation of diacylglycerol (DAG). DAG can be formed from PtdInsP2 by the action of phospholipase C (PL-C). Another pathway starts from phosphatidyl chohne. Phospholipase D (PL-D) converts phosphatidyl choline to phosphatidic add (Ptd), and the action of phosphatases results in DAG. Arachidonic add, the starting point of biosynthesis of prostaglandins and other intracellular and extracellular messenger substances, can be cleaved from DAG. PKC protein kinase C Ptdins phosphatidyl inositol.

Two fatty acids are dietary essentials in humans (see p. 361) linoleic acid, which is the precursor of arachidonic acid, the sub strate for prostaglandin synthesis (see p. 211), and linolenic acid, the precursor of other co-3 fatty acids important for growth and development. [Note A deficiency of linolenic acid results in decreased vision and altered learning behaviors.] Arachidonic add becomes essential if linoleic acid is deficient in the diet. 

Platelets can inactivate PAF by the inverse sequence deacetylation followed by acylation with arachidonic add. PAF can also be hydrolyzed by a PAF acetylhydro-lase, a phospholipase.0 Absence of this enzyme in the brain may be related to a human brain malformation.11 Some tissues may contain a lipid that inhibits binding of PAF.p The following compound from a Chinese herb binds to PAF receptors and may be the forerunner of useful drugs. )... 

Fig.4.16. Separation of some 2-naphthacyl esters of fatty adds. A, C, adds B, C adds. Peaks 1 = oleic add 2 = linoleic add 3 a-Unolenic add 4 = 7-linolenic add 5 = dihomo-7-linolenic add 6 = arachidonic add 7 = 2-naphthacyl bromide. (From ref. 40 with permission of the American Chemical Society, Washington.)...

Murakami, M., Kambe, T., Shimbara, S., Higashino, K., Hanasaki, K., Arita, H., Horiguchi, M., Arita, M., Arai, H., Inoue, K. and Kudo, I., 1999, Different functional aspects ofthe group II subfamily (Types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic add release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation../. Biol. Chem., 274 31435-31444. 

Huwiler, A., Johansen, B., Skarstad, A. and Pfeilschifter, J., 2001, Ceramide binds to the CaLB domain of cytosolic phospholipase A2 and facilitates its membrane docking and arachidonic add release. FASEB J. 15 7-9... 

Note, too, the mild conditions used for the formation of the diisopropyl acetal 552 from aldehyde 55,1 again without p-elimination. Another example comes from a synthesis of Arachidonic Add in which a key step was the mild hydrolysis of a diisopropyl acetal under conditions that do not provoke rearrangement of the p,y-double bond into conjugation with the aldehyde function.118 The method has been applied to the synthesis of a number of natural (Z,Z)-skipped 1,4-dienes.119... 

Chan PH, Fishman RA (1984) The role of arachidonic add in vasogenic brain edema. Fed Proc 43 210-213... 

Moncada, S. and Vane, J.R., Interaction between anti-inflammatory dmgs and inflammatory mediators. A reference to products of arachidonic add metaboUsm, Agents Actions Suppl. 3, 141-149,1977 Moncada, S. and Higgs, E.A., MetaboUsm of arachidonic add, Ann. N.Y.Acad. Sci. 522,454-463,1988 PiomelU, D., Arachidonic add in cell signaling, Curr. Opin. Cell Biol. 5,274-280, 1993 Janssen-Timmen, U., Tomic, I., Specht, E. et al.. The arachidonic acid cascade, eicosanoids, and signal transduction, Ann. N.Y. Acad. Sci. 733, 325-334, 1994 Wang, X. and Stocco, D.M., Cyclic AMP and arachidonic acid a tale of two pathways. Mol. Cell. Endocrinol. 158, 7-12, 1999 Brash, A.R., Arachidonic acid as a bioactive molecule, J. Clin. Invest. 

Blackwell GJ, Duncombe WG, Flower RJ, Parsons MF, and Vane JR. (1977). The distribution and metabolism of arachidonic add in rabbit platelets during aggregation and its modification by drugs. Br. J. Pharmacol. 59,353-366. 

Hashizume T, Taniguchi M, Sato T, and Fujii T. (1994). Arachidonic add liberation induced by phosphatidic acid endog usly generated fiom membrane fiiospholipids in rabbit platelets. Biodiim. Bio diys. Acta. 1221,179-184. 

Nakatsuka M, Osawa Y (1994) Selective inhibition of the 12-lipoxygenase pathway of arachidonic add metabolism by L-arginine or sodium nitroprusside in intact human platelets. Biodiem Biophys Res Coriunun 200 1630-1634. 

Converts arachidonic add into prostaglandin H2 rate-hmiting step in prostaglandin synthesis Converts arachidonic add into prostaglandin H2 rate-hmiting step in prostaglandin synthesis ... 

The first step in the formation of the leukotrienes is cleavage of arachidonic add from membrane phospholipids. 5-I.ipoxygcnasp, which is a calcium-dependent enzyme, catalyzes the introductionof Oi into the arachidonic add and the conversion of the resulting hydroperoxide to an epoxide. Leukotriene A, contains an epoxide group. Leukobiene (LTA ) can be converted to leukotriene B (LTB4) by enzymatic hydrolysis. LTB is a dihydroxy fatty acid it regulates the functions... 

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