Arachidonic acid enzymatic conversion

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. 

Nakane, S., Oka, S., Arai, S., Waku, K., Ishima, Y., Tokumura, A., and Sugiura, T. (2002). 2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid Occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain. Arch. Biochem. Biophys. 402, 51-58. 

Conversion of arachidonic acid to an eicosanoid y-ketoaldehyde can proceed by two separate pathways, one driven enzymatically by cyclooxygenases and the other driven non-enzymatically by free radicals. The two pathways differ only in the mechanism used to generate the key intermediate, a bicyclic endoperoxide with two aliphatic side chains, which can undergo non-enzymatic rearrangement to... 

Several reports have suggested an association between 5-LOX, 5-(S)HETE formation and carcinogenesis. The expression of 5-LOX has been documented in several cancers including prostate, colon, lung, breast, pancreas, bone, brain, and mesothelium (Romano Claria, 2003). Inhibition of 5-LOX enzymatic activity by specific chemical inhibitors blocked the stimulatory effect of arachidonic acid on the growth of prostate cancer cells. Conversely, addition of 5-HETE but not leukotrienes promoted the growth of prostate cancer cells. 

Arachidonic acid (20 4n - 6) is one of two major PUFA synthesized by the D6D/D5D pathway (Fig. 4). In many tissues and cell types, 20 4n - 6 is esterified to the sn-2 position of membrane PL, and is used for the eicosanoid-mediated signaling to perform specialized cell functions. Arachidonic acid esterified in PL is a storage form of this fatty acid and is hydrolyzed from the PL by phospholipases prior to enzymatic conversion into eicosanoids (Chapter 13). Eicosanoids are autocrine/paracrine hormones that mediate a variety of localized reactions, such as inflammation, homeostasis, and protection of digestive tract epithelium. D6D deficiency in humans leads to severe food intolerance and growth retardation (J. Nwankwo, 2003). These symptoms are reversed by arachidonic acid supplementation to the diet, which supports the essential role of eicosanoids in the protection of digestive tract mucosa in humans. 

There are many unanswered questions about the dual role that ether lipids serve as membrane components and as cellular signaling molecules. Although it is clear that arachidonic acid is closely associated and tenaciously retained by ether lipids in membranes, even in essential fatty acid deficiency, much remains to be elucidated about the enzymatic systems and regulatory controls that affect the release of this sequestered pool of arachidonic acid for its subsequent conversion to bioactive eicosanoid metabolites. The significance of ether lipids as a dietary nutrient has received little attention even though they occur in a variety of foods and it is known that ether lipid supplements are readily incorporated into cellular lipids. 

An important fate of arachidonic acid is enzymatic conversion to prostaglandins by one of two prostaglandin G/H synthases [23]. As described in Chapter 12, these enzymes have... 

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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