Arachidoic acid

Non-steroidal antiinflammatory drugs (NSAIDs) are the main therapeutic agents for the treatment of the symptoms of arthritis. The drugs seem to inhibit the enzyme cyclooxygenase and consequently the conversion of arachidoic acid into prostaglandins. The main drawbacks of NSAIDs are severe side effects, including gastrointestinal ulceration and... 

Recently, Gunther et al. [41] proposed that nitric oxide may directly react with enzymes without intermediate formation of peroxynitrite. It is known that the oxidation of arachido-nic acid by prostaglandin H oxidase is mediated by the formation of enzyme tyrosyl radical (see Chapter 26). Correspondingly, it has been suggested that NO is able to react with this radical to form the tyrosine iminoxyl radical and then nitrotyrosine. Therefore, the NO-dependent nitration of protein tyrosine residue may occur without the formation of peroxynitrite or other nitrogen oxides. 

This enzyme [EC 6.2.1.15], also known as arachido-nateiCoA ligase, catalyzes the reaction of arachidonate with ATP and coenzyme A to generate arachidonyl-CoA, AMP, and pyrophosphate (or, diphosphate). The enzyme can also use 8,11,14-icosatrienoate as a substrate, but not the other long-chain fatty acids. It should be noted that this enzyme is not identical to long-chain acyl-CoA synthetase [EC 6.2.1.3]. 

Figure 6-16. Prostaglandins, thromboxanes, and leukotrienes. For each of the classes of prostaglandins (H, E, F, A), the ring contains hydroxyl and keto groups at different positions. Only the ring portions of PGE2, PGF2ct, and PGA2 are shown. The remainder of the molecule (not shown) is the same as PGH2. The subscript refers to the number of double bonds in the nonring portion. The class with two double bonds is derived from arachido-nate. Other classes (with one or three double bonds) are derived from other polyunsaturated fatty acids.

A. Schmidt, M. Wolde, C. Thiele, W. Best, H. Kratzin, A.V. Podtelejnikov, W. WiTKE, W.B. Huttner, and H.D. Soling. Endophilin I mediates synaptic vesicle formation by transfer of arachido-nate to lysophosphatidic acid. Nature, 1999, 403, 133-141. 

Soling, Endophilin I mediates synaptic vesicle formation by transfer of arachido-nate to lysophosphatidic acid. Nature,... 

Witting A, Walter L, Wacker J, Moller T, Stella N (2004) P2X7 receptors control 2-arachido-noylglycerol production by microglial cells. Proc Natl Acad Sci U S A 101 3214-3219 Xiao AZ, Zhao YG, Duan EK (2002) Expression and regulation of the fatty acid amide... 

Linoleate, although high in the diet, cannot be synthesized in the human and is an essential fatty acid. It is required for formation of arachido-nate, which is present in plasma lipids, and is used for eicosanoid synthesis. Therefore, only a portion of the linoleate pool is rapidly oxidized. 

FIGURE 3.23 Biosynthesis of anandamide. Phosphatidylethanolamine (PE) is condensed with an arachido-nate (C20 4ffl6) group given by a glycerophospholipid (not shown) in a reaction catalyzed by N-acyltransferase. This results in the synthesis of N-arachidonoyl PE, the precursor of anandamide. Then, this precursor is cleaved into anandamide and phosphatidic acid (PA) by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). 

This idea is depicted schematically in Figure 2.7. Incorporation of arachidonic acid into phospholipids depends on arachido-noyl-CoA lysophospholipid transferase activity. Because arachidonate is converted very rapidly to arachidonoyl-CoA within cells, this reaction is unlikely to be rate-limiting. But what about the... 

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