Arachidonic acid lipoxygenase metabolites

Any of the collection of oxygenated metabolites of arachidonic acid that are the product of cyclooxygenase, cytochrome P450, or lipoxygenase pathways. 

The title compounds LTB4, 21 (Z) and 22 (Z), have been synthesized23 by stereoselective reduction with deuterium gas of a 1 1 mixture of the suitable diacetylenic precursors 23 and 24 using Lindlar catalyst or palladium on barium sulphate catalyst (equation 10). Leukotriene B4, a 5-lipoxygenase metabolite of arachidonic acid, playing... 

The title compound 160, a biologically potent metabolite of arachidonic acid metabolism, produced in the 5-lipoxygenase pathway in some mammalian cells127 128, has been synthesized129-131 by the reaction of leukotriene E4, 161, with [l-nC[acetyl chloride in 1.3% yield based on [l-nC] acetyl chloride129 (equation 55). 

The biological actions of the cysteinyl leukotrienes are mediated via stimulation of CysLTi receptors. Montelukast and zafirlukast are competitive antagonists of these receptors. In contrast, zileuton suppresses synthesis of the leukotrienes by inhibiting 5-lipoxygenase, a key enzyme in the bioconversion of arachidonic acid to the leukotrienes. Zileuton also blocks the production of leukotriene B4, another arachidonic acid metabolite with proinfiammatory activity. The CysLTi-receptor antagonists alter neither the production nor the actions of leukotriene B4. 

Massey KD, Minnich BN, Burt JM Arachidonic acid and lipoxygenase metabolites uncouple neonatal rat cardiac myocyte pairs. Am J Physiol 1992 263 C494—C501. 

Figure 2 Known second-messenger pathways that modulate capsaicin or VRs. GPCR, G protein-coupled receptors PLA2, phospholipase A2 AC, adenylate cyclase IP3, inositoltriphosphate DAC diacylglycerol LM, lipoxygenase metabolites AA, arachidonic acid ANA, anandamide PG, prostaglandins Gq/11, Gq/j, Gs, trimeric G-proteins (adapted from Premkumar, 2001)...

GRF-stimulated GH release is also inhibited by lipoxygenase inhibitors, suggesting participation of some lipoxygenase product(s). However, in this area of research more work is also required to attribute a specific messenger role to these arachidonic acid metabolites. 

Powell WS (1985) Reversed-phase high-pressure liquid chromatography of arachidonic acid metabolites formed by cyclo-oxygenase and lipoxygenases. Analyt Biochem 148 59-69... 

Piomelli, D. and Greengard, P. (1990). Lipoxygenase metabolites of arachidonic acid in neural transmembrane... 

Takenaga M, Hirai A, Terano T, Tamura Y, Kitagawa H and Yoshida S. (1986). Comparison < the in vitro effect of eicosapentaoioic acid (EPA) -derived lipoxygenase metabolites on human platelet function with those of arachidonic acid. Throm. Res. 37,373-384. 

Lipoxygenase metabolites of arachidonic acid such as 12-hydroxyeicosa-tetraenoic acid (12-HETE) have been shown to be involved in the release of neurotiansmitters and other cellular functions (92-94). Basal generation of 12-HETE has been reported to be about 3.7-fold greater in SHR than in WKY platelets (95,96). Arachidonic acid has been shown to stimulate platelets by activating protein kinase C, by a prostaglandin-independent mechanism (97). It is possible that the lipoxygenase metabolites of arachidonic acid may also be involved in altered reactivity in hypertension. 

Lipoxygenase metabolites of arachidonic acid as second messoigers for presfynaptk inhibition of lysia sensory cells. Nature, 328,38-43,1987. 

Arachidonic acid can also be metabolized to a variety of mediators, depending on the cell type. For example, lipoxygenase catalyzes the production of leu-kotrienes, and mixed-function oxygenases catalyze the production of epoxyeicosatrienoic acids. Collectively, these oxygenated metabolites may play a critical role in NSAIEt-induced nephrotic syndrome by shunting arachidonic acid metabolism from prostaglandins to... 

Two pathways of metabolism are available for arachidonic acid. The first is the cyclooxygenase pathway, which leads to the formation of prostaglandins, thromboxanes, and prostacyclin. The second is the lipoxygenase pathway. Lipoxygenase catalyzes the first step in the conversion of arachidonic acid to a number of noncyclized metabolites. These metabolites include 5-hydroperoxyei-cosatetraenoic acid (HPETE) and the leukotrienes (Figure 9.101). 

Platelets in hypercholesterolemic patients are more susceptible to aggregation than normal subjects [72]. Aggregation is mediated by several mediators, including cyclooxygenase and lipoxygenase metabolites of arachidonic acid [73]. A deficiency of vitamin E enhanced eicosanoid production in platelets [74,75]. 

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