Arachidonic acid, structure

Blank, I., Lin, J., Arce Vera, F, Welti, D.H., Fay, L.B. Identification of potent odorants formed by autoxidation of arachidonic acid structure elucidation and synthesis of ( ,Z,Z)-2,4,7-tiidecatrie-nal. J. Agric. Food Chem. 2001, 42, 2959-2965. 

Leukotrienes (LTs) are lipid mediators derived enzymatically from arachidonic acid. Structurally, these eicosanoids contain a conjugated triene functionality. LTB4 and LTC4 are the two important leukotrienes. Mass spectrometry has played... 

The prostaglandins (qv) constitute another class of fatty acids with aUcycHc structures. These are of great biological importance and are formed by i vivo oxidation of 20-carbon polyunsaturated fatty acids, particularly arachidonic acid [27400-91-5]. Several prostaglandins, eg, PGE [745-65-3] have different degrees of unsaturation and oxidation when compared to the parent compound, prostanoic acid [25151 -18-9]. 

Hepoxylins are metabolites of arachidonic acid which arise from 12-HPETE in tissues such as pancreatic islet cells (where they stimulate glucose-dependent insulin release) and brain (where they appear to have a neuromodulatory role). The structure of the hepoxylins was confirmed by synthesis which also has provided this scarce material for biological investigation. 

Draw the structures of (a) all the possible triacylglycerols that can be formed from glycerol with stearic and arachidonic acid, and (b) all the phosphatidylserine isomers that can be formed from palmitic and linolenic acids. 

In this bromoaspirin-inactivated structure, Ser , which lies along the wall of the tunnel, is bromoacetylated, and a molecule of salicylate is also bound in the tunnel. Deep in the tunnel, at the far end, lies Tyr, a catalytically important residue. Heme-dependent peroxidase activity is implicated in the formation of a proposed Tyr radical, which is required for cyclooxygenase activity. Aspirin and other NSAIDs block the synthesis of prostaglandins by filling and blocking the tunnel, preventing the migration of arachidonic acid to Tyr in the active site at the back of the tunnel. 

Compounds 111 having structural features of the dual cyclooxygenase (COX)/5-lipooxygenase (5-LO) inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared. Many of these hybrid compounds are potent COX and 5-LO inhibitors two compounds (111, r =McO, R = R" = R = H, R = NH2, R = Me and r = MeO, R = R = Me, R" = R = H, R = Cl) inhibited eicosanoid biosynthesis in an ex vivo assay, but neither improved on the main deficiency of tepoxalin, duration of 5-LO inhibitory activity (99BMCL979). Compounds 111 inhibit the production of arachidonic acid products associated with 5-lipoxygenase and cyclooxygenase and are useful in the treatment of inflammatory disorders (99USP5925769). 

Figure 27.3 Structures of some representative eicosanoids. All are derived biologically from arachidonic acid.

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Arabinose, configuration of. 982 Kiliani-Fischer synthesis on. 995 Arachidic acid, structure of, 1062 Arachidonic acid, eicosanoids from, 1069-1070... 

A non-allergic mechanism imderlying precipitation of asthmatic attacks by aspirin in hypersensitive patients was proposed over 30 years ago [4]. It was founded on pharmacological inhibition of COX of arachidonic acid and explained a cross-reactivity between different NSAIDs varying in chemical structure. This COX theory was confirmed by several studies [11] and was further refined following discovery of the second COX isoenzyme - COX-2. At least two COX isoenzymes, COX-1 and COX-2, are coded by separate genes. Their role in inflammation, asthma and anaphylaxis has been reviewed previously [12]. 

Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the stmctural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane. 

A series of 4-arylpyrimidines that arc amine substituted at pyrimidine C-2 was prepared. FK360 was most effective from this group on both arachidonate-induced cerebral oedema in rats and as an in vitro inhibitor of lipid peroxidation. The authors link effects of FK360 to the arachidonic acid cascade (Kuno et al., 1992). This is an unusual structure. 

The source of free radicals is multiplied under these circumstances, arachidonic acid metabolism, activation of xanthine oxidase, perturbation of electron flow within the respiratory chain, and NOS activation. Structurally, excitotoxicity is generally described as a necrotic process involving initial swelling of the cell and of the endoplasmic reticulum, clumping of chromatin, followed by swelling of the... 

Addition of RNA or DNA prior to oxidation of BP by PGH synthase results in substantial nucleic acid binding (17,21). Addition of RNA five minutes after initiation of oxidation leads to no covalent binding (17). This implies that the quinones do not bind to nucleic acid but rather a short-lived intermediate in their formation does. Arachidonic acid oxygenation in ram seminal vesicle microsomes is complete within two min, which suggests that the reactive intermediate is generated concurrently with PGH2 The structures of the nucleic acid adducts have not been elucidated so the identity of the reactive intermediate is unknown. 

Figure 7. Dependence of BP oxidation by ram seminal vesicle micro-somes on the concentration of different hydroperoxides. Abbreviations used are 20 4, arachidonic acid 15-HPEA, 15-hydroperoxy-eicosatetraenoic acid t-BuOOH, t-butyl hydroperoxide. The structure is PGG2 is given in Figure 1.

Lipids have multiple roles in cells. Recent discoveries show that the same lipid may have both structural and regulatory roles in the cell. For example, while arachidonic acid (20 4co6) is a major constituent of brain inositides and PtdEtn, the free acid is also a precursor of a number of important bio messengers, the eicosanoids, such as prostaglandins, prostacyclins, leukotrienes and thromboxanes... 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

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