Fatty acids lipoxygenase pathway

The major metabolites of arachidonic acid (Figure 18-19) arise from the 12-lipoxygenase, the 5-lipoxygenase, and the fatty acid cyclooxygenase pathway. The 5-lipoxygenase pathway yields leukotrienes, and the cyclooxygenase pathway yields cyclic endoperoxides, which are converted to PGs, TXs, and PGIs. 

The non-specific lipoxygenases can cooxidize carotenoids and chlorophyll and thus can degrade these pigments to colorless products. This property is utilized in flour bleaching (cf. 15.4.1.4.3). The involvement of LOX in cooxidation reactions can be explained by the possibility that the peroxy radicals are not as rapidly and fully converted to their hydroperoxides as in the case of specifically reacting enzymes. Thus, a fraction of the free peroxy radicals are released by the enzyme. It can abstract an H-atom either from the unsaturated fatty acid present (pathway 2a in Fig. 3.30) or from a polyene (pathway 2b in Fig. 3.30). 

Figure 4. Major fatty acid oxygenase pathways - lipoxygenase, hydroperoxide isomerase and lipoxins. Adapted from (37).

There are three groups of eicosanoids that are synthesized from C20 eicosanoic acids derived from the essential fatty acids linoleate and a-linolenate, or directly from dietary arachidonate and eicosapentaenoate (Figure 23-5). Arachidonate, usually derived from the 2 position of phospholipids in the plasma membrane by the action of phospholipase Aj (Figure 24-6)—but also from the diet—is the substrate for the synthesis of the PG2, 1X2 series (prostanoids) by the cyclooxygenase pathway, or the LT4 and LX4 series by the lipoxygenase pathway, with the two pathways competing for the arachidonate substrate (Figure 23-5). 

The lipase-catalyzed fatty acid ester hydrolysis and the lipoxygenation of free polyunsaturated fatty acids are involved in the same lipid degradation pathway. They are respectively the first and second reaction in the lipoxygenase pathway (Fig. 3) [87-91]. The pathway produces volatile products of considerable importance in food technology including Cg[92, 93] or Cg- 94—96 aldehydes and alcohols from polyunsaturated fatty... 

At the end of the reaction, hydroperoxide can be easily recovered in the aqueous phase (98-99%) after its separation from the organic phase and precipitation of the enzymes. The hydroperoxides obtained are highly reactive molecules [109]. They are intermediate compounds in the lipoxygenase pathway in plants, precursors for the synthesis of hydroxy-fatty acids (i.e., ( + )-coriolic acid [38,110], and regulators of the prostaglandins biosynthesis [111-113]. 

Figure 1.9. Overview of the biosynthesis of ecosanoids. The 20 carbon fatty acid arachidonic acid is released from cell membrane phospholipids by the actions of phospholipase A2. Free arachidonic acid forms the precursor of prostaglandins and thromboxanes via the multi-enz5une cyclooxygenase pathway, while leukotrienes are formed via the lipoxygenase pathway...

The eicosanoids, so called because of their derivation from a 20-carbon unsaturated fatty acid, arachidonic acid (eicosatetraenoic acid), are obtained from membrane phospholipids and synthesized de novo at the time of cellular stimulation. Arachidonic acid is cleaved from membrane-bound phosphatidylcholine by the enzyme phospholipase A2. Alternatively, arachidonic acid may be derived by the sequential actions of phospholipase C and diacylglyceryl lipase. Arachidonic acid can then follow either of two enzymatic pathways that result in the production of inflammatory mediators. The pathway initiated by cyclooxygenase (COX) produces prostaglandins the lipoxygenase pathway generates leukotrienes (Fig. 36.2). 

Synthesis of prostaglandins and thromboxanes begins with the oxidative cyclization of free arachidonic acid to yield PGH2 by prostaglandin endoperoxide synthase—a microsomal protein that has two catalytic activities fatty acid cyclooxygenase (COX) and peroxidase. There are two isozymes of the synthase COX-1 and COX-2. Leukotrienes are produced by the 5-lipoxygenase pathway. 

The lipoxygenase system also competes for released arachidonic acid in a way that seems to be tissue-selective, giving rise to hydroperoxy fatty acids (HPETE) which can be converted into leukotrienes or reduced to hydroxy fatty acid (HETE) products [115]. The basic scheme for these metabolic conversions involving arachidonic acid is presented in Figure 5.2. Both of the main enzymatic pathways of arachidonic acid metabolism are thought to involve free-radical-mediated reactions [108] and the antioxidant capacity of vitamin E could therefore allow the vitamin to modify the products of these pathways. 

FIGURE 7.6 Short-chain aldehydes and alcohols produced from the degradation of fatty acids in grapes via the lipoxygenase (LOX)/hydroperoxide lyase (HPL) pathway during the prefermentative stages of vinification (adapted from Camara, 2004). 

Fig. 1. Targeted lipidomics of anandamide metabolism. Postulated pathways of anandamide metabolism. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine NAT, JV-acyl transferase LPA, lysophosphatidic acid PA, phosphatidic acid NAPE, jV-acyl-phosphatidylethanolamine Lyso-NAPE, l-lyso,2-acyl-OT-glycero-3-phosphoethanolamine-JV-acyl ABHD-4, a//3 hydrolase-4 GP-anandamide, glycerophospho-anandamide PAEA, phospho-anandamide PLA, phospholipase A NAPE-PLD, NAPE phospholipase D PLC, phospholipase C FAAH, fatty acid amide hydrolase P, phosphatase COX, cyclooxygenase LOX, lipoxygenase CYP450, cytochrome P450 PDE, phosphodiesterase.

The EFA stored in the phospholipids of cell membranes are released by phospholipases, and then undergo oxidative transformation by the cyclooxygenase (COX) pathway to prostanoids and by the lipoxygenase pathway to hydroxy fatty acids and leukotrienes. The metabolism to prostanoids is catalyzed by two isoenzymes of COX, a constitutive (COX-1) and an inducible form (COX-2). The main products of COX metabolism of AA are prostaglandin E2 (PGE2), PGI A, and PGD2. In addition, A A is converted via 15-lipoxygenase to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins, by... 

The volatile fraction of good quality oils is mainly formed by compounds produced enzymatically from polyunsaturated fatty acids through the lipoxygenase (LOX) pathway. Aldehydes (C6), alcohols (C6) and their corresponding esters are the most abundant products (Figure 2.7). 

JAs are derived from linolenic acid via an octadecanoid pathway consisting of several enzymatic steps (Figure 36). Multiple compartments in plant cells participate in JA synthesis. The early steps of this pathway occur in chloroplasts, where linolenic acid is converted to OPDA by means of the three enzymes lipoxygenase (LOX), allene oxide synthase (AOS), and allene oxide cyclase (AOC).867-869 Linolenic acid is oxygenated by 13-LOX producing a peroxidized fatty acid 13-hydroperoxylinolenic acid. The product is subsequently metabolized by AOS to an unstable compound allene oxide. Allene oxide is sequentially converted by AOC to produce OPDA. An alternative pathway from another trienoic fatty acid, hexadecatrienoic acid (16 3), is present in chloroplasts.870 In this pathway, dinor OPDA is produced instead of OPDA. OPDA and dinor OPDA are transported into the peroxisome. An ABC transporter involved in this transport was identified in... 

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