Lipoxygenases synthesis

Oelze-Karow et al. (44) assert that lipoxygenase production in the seedlings of mustard, Sinapis alba, is under phytochrome control. When the far-red form of the pigment reaches a threshold level, lipoxygenase synthesis is rapidly repressed. When the concentration of the far-red form drops below this value, synthesis begins immediately. 

Synthesis of a Class of Sulfur-Containing Lipoxygenase Inhibitors.351... 

Fluormated agents such as flurbiprofen (II), flunisal(i2), diflunisal (13), and sulindac (14), acting as prostaglandin synthesis mhibitors, have been available for some time [5] The recent introduction of flunoxaprafen (15), a lipoxygenase inhibitor, is notable It reportedly produces considerably less severe gastric disturbance [75]... 

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

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). 

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]. 

PGH synthase and the related enzyme lipoxygenase occupy a position at the interface of peroxidase chemistry and free radical chemistry and can clearly trigger metabolic activation by both mechanisms. The peroxidase pathway activates compounds such as diethylstilbestrol and aromatic amines whereas the free radical pathway activates polycyclic hydrocarbons (59). Both pathways require synthesis of hydroperoxide in order to trigger oxidation. 

The other major arachidonic acid (AA) converting enzyme is an integral binding protein, 5-lipoxygenase, which is responsible for the initial transformation in a cascade of events towards the biosynthesis of leukotrienes. Leukotrienes are major mediators of numerous biological processes, including chemotaxis, and are implicated in hypersensitivity disorders like asthma. It was discovered in the early 1990s that another protein is necessary for the cellular synthesis of... 

Eicosanoid synthesis. Arachidonic acid is converted by cyclooxygenases into prostaglandins, and thromboxanes. Lipoxygenases convert arachidonic acid into HPETEs, which are then converted to lipoxins, leukotrienes, and 12-HETE (hydroxyeicosatetraenoic acid). Epoxygenases convert arachidonic acid into epoxides. 

Another mechanism that potentially contributes to clove oil s effects is inhibition of prostaglandin synthesis through both cyclooxygenase and lipoxygenase pathways (Tyler 1994). Accordingly, local injections of clove oil supressed joint swelling in arthritic rats (Sharma et al. 1994). 

Brock TG. (2005) Regulating leukotriene synthesis the role of nuclear 5-lipoxygenase. J Cell Biochem. 96, 1203-1211. 

Hydroperoxides play an important role as oxidants in organic synthesis [56-58]. Although several methods are available for the preparation of racemic hydroperoxides, no convenient method of a broad scope was until recently [59] known for the synthesis of optically active hydroperoxides. Such peroxides have potential as oxidants in the asymmetric oxidation of organic substrates, currently a subject of intensive investigations in synthetic organic chemistry [60, 61]. The application of lipoxygenase [62-65] and lipases [66,67] facilitated the preparation of optically active hydroperoxides by enzymes for the first time. 

Before taking leave of the eicosanoids, 1 need to point out that a second enzyme, 5-lipoxygenase, also metabolizes arachidonic acid. 5-Lipoxygenase initiates the synthesis of the leukotrienes from arachidonic acid. There is a whole family of leukotrienes and these molecules have a spectrum of biological properties. 1 will focus on one important leukotriene, LTB4. 

The cooperative effect of MeO and the oxazoline directs the lithiation of 60 in this synthesis of a lipoxygenase inhibitor AC-5-1 61 (Scheme 30) °. ... 

In 1990, Triantaphylidds and coworkers reported on the preparative enzymatic synthesis of hnoleic acid (135) hydroperoxide 24a using soybean lipoxygenase-1. In this dioxygenation asymmetry is induced by the catalyst, the enzyme. The reaction was later used by Dussault and also by Baba and coworkers as key step in the preparation of more complex peroxides. The enzyme is a non-heme iron dioxygenase which catalyzes the incorporation of dioxygen into polyunsaturated fatty acids to yield E,Z conjugated diene hydroperoxides 24a-d. With this enzymatic method, the hydroperoxide 24a could... 

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. 

Zileuton Inhibits lipoxygenase, reduces synthesis of leukotrienes ... 

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