Arachidonic acid oxidation

Fam SS, Morrow JD. The isoprostanes unique products of arachidonic acid oxidation a review. Curr. Med. Chem. 10, 1723-1740, 2003. 

Without enzymatic catalysis, the endo and bicyclic peroxides (Reaction 46a) usually account for less than a few percent of arachidonic acid oxidation products, and the dominant pathways are formation of exo peroxides (Reaction 45) and polyperoxides (Reaction 46b). 

Figure 6. Stimulation by human LDL of the arachidonic acid oxidation catalyzed by C-15 animal lipoxygenase (reticulocyte lipoxygenase) (1), in the absence of LDL (2), in the presence of LDL.

Mitochondria are the site of ROS production during ischemia. Arachidonic acid, eNOS, NADPH oxidase and xanthine oxidase are sources of reactive oxygen species at reperfusion. Cytochrome P450 monooxygenases (CYPs) have also been implicated. CYP catalyzes arachidonic acid oxidation to a variety of biologically active eicosanoids and generates reactive oxygen species.1 3... 

Penneys NS. Inhibition of arachidonic acid oxidation in vitro by vehicle components Acta Dermatovener 1982 62 59-61. 

For these reasons, and because they can be measured in urine and plasma, PGF are generally considered to offer a noninvasive, sensitive, specific direct method for measuring lipid peroxidation in vivo (Y1). The main drawback is that the methods are very complicated, tedious, and not usually available in clinical laboratories. Like other lipid oxidation products, PGF can be generated ex vivo. For this reason, fluids should be preserved with butylated hydroxy toluene (BHT) and EDTA to prevent further oxidation and measured immediately or stored at —70°C (M8). An ELISA has been developed for urine for 8-Iso-PGF2a that is commercially available (02), but the method is tedious since it requires a column separation prior to ELISA (Bl). Also, since PGF are mainly indicators of arachidonic acid oxidation, they do not reflect oxidation of the major PUFA comprising lipoproteins. 

Fig. 5. Some reactive aldehydes. MDA is a specific 3-carbon product of arachidonic acid oxidation. 4-hydroxy-2-alkenals is the general class of lipid peroxidation-related aldehydes to which the specific product HNE belongs (Ul).

Fig. 5.5 Chemical structures of dantrolene, a muscle relaxant (a) monocycUne, abroad-spectrum tetracyclin antibiotic (b) docosahexaenoic add, a arachidonic acid oxidation inhibitor (c) and polyethylene glycol (d)...

The major issue with P450 2J2 is its role in endogenous metabolism (i.e., arachidonic acid oxidation) and the etiology of several diseases, including hypoxia [1161], cardiotoxicity [1162, 1163], coronary artery disease [1164-1167], myocardial infarction [1168-1170], atherosclerosis [1171], hypertension [1172, 1173], asthma [1174], stroke [1169, 1175], hyperhomocyste-inemia [1176], diabetes [1177], preeclampsia [1178], Crohn s disease [1179], and others [1130, 1180-1182]. 

Fam, S. S. and Morrow, J.D. The isoprostanes Unique products of arachidonic acid oxidation -A review. Current Medicinal Chemistry, 10, 1723-1740(2003). 

Rich AM, Weissman G, Anderson C, et al. Calcium-dependent aggregation of marine sponge cells is provoked by leukotriene B4 and inhibited by inhibitors of arachidonic acid oxidation. Biochem Biophys Res Commun 1984 121 863-870. 

CifiHjjOi. A fatly acid which is easily oxidized in air.-It occurs widely, in the form of glycerides, in vegetable oils and in mammalian lipids. Cholesieryl linoleale is an important constituent of blood. The add also occurs in lecithins. Together with arachidonic acid it is the most important essential fatty acid of human diet. 

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]. 

Extracts from Clavularia viridis and also many other coral species convert arachidonic acid to the prostanoidpreclavulone-A via 8-( f )-hydroperoxy-5,ll,14( Z), QfEj-eicosatetraenoic acid. The carbocyclization is considered to occur from allene oxide and oxidopentadienyl cation intermediates. An enantioselective total synthesis of preclavulone-A was developed to assist the biosynthetic research. 

Write properly balanced chemical equations for the oxidation to COg and water of (a) myristic acid, (b) stearic acid, (c) a-linolenic acid, and (d) arachidonic acid. 

All prostaglandins are cyclopentanoic acids derived from arachidonic acid. The biosynthesis of prostaglandins is initiated by an enzyme associated with the endoplasmic reticulum, called prostaglandin endoperoxide synthase, also known as cyclooxygenase. The enzyme catalyzes simultaneous oxidation and cyclization of arachidonic acid. The enzyme is viewed as having two distinct activities, cyclooxygenase and peroxidase, as shown in Figure 25.28. 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Adler, K.B., Akiey, N.J. and Holdenstaufier, W.J. (1989). Exposure of airway epithelium to extracellular oxidants in vitro stimulates arachidonic acid metabolism and mucin secretion. Am. Rev. Resp. Dis. 139, A403. 

There is some evidence that in cells with low anandamide amidase activity, such as platelets and neutrophils, anandamide is inactivated by an oxidative pathway involving 12(5)-lipoxygenase (Edgemond, 1998). Metabolism of anandamide by enzymes of the arachidonic acid cascade... 

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