5-lipoxygenase enzymatic activity

Hyperforin, the major constituent in Hypericum perforatum (St. John s Wort), inhibits the enzymatic activity of 5-lipoxygenase and COX-1 in platelets, acts as a dual inhibitor of 5-lipoxygenase and COX-1, and might have some potential in inflammatory and allergic diseases connected to eicosanoids (32), Several Hypericum species are of medicinal value in Asia and the Pacific. One of these is Hypericum erectum Thunb., the potential of which as a source of 5-lipoxygenase is given here. 

Lopez-Nicolas JM, Perez-Gilabert M and Garcia-CarmonaF. 2001. Eggplant lipoxygenase (Solatium melon-gena) product characterization and effect of physicochemical properties of linoleic acid on the enzymatic activity. J Agric Food Chem 49(l) 433-438. 

Royo, J., Vancanneyt, G., Perez, A. G., Sanz, C., Stormann, K., Rosahl, S., Sanchez-Serrano, J. J. (1996). Char-aeterization of three potato lipoxygenases with distinct enzymatic activities and different organ-specific and wound-regulated expression patterns. J. Biol. Chem., 271, 21012-21019. 

The committed biosynthetic path to the leukotrienes begins (see Fig. 5.2) with the action of 5-lipoxygenase (5-LO)[EC 1.13.11.34] (14)on arachidonic acid. Purified human 5-LO is an unstable, 78,000-Da protein that has been isolated and cloned (15,16). It contains a tightly bound, nonheme iron that is essential for enzymatic activity (17). Like all known lipoxygenases, 5-LO catalyzes the insertion of molecular oxygen into a l,4-cis,cis-pentadiene unit. The effect of 5-LO on AA is to abstract stereospecifically the pro-S hydrogen at position C7 and to insert molecular oxygen at... 

There are many studies about the relation between the free oxygen radical scavenging activities of many flavonoids and their effects on the enzymes which take part in the metabolism of arachidonic acid, cyclooxygenase (COX) and lipoxygenase (LOX). Duneic [182] shows that the antiradical action affects the COX activity in several ways. In most of the cases, at high substrate concentrations the enzymatic activity was intensified and at low concentrations it was inhibited. Apparently, the influence of the antiradical properties on the activity of enzymatic metabolism of the arachidonic acid in vitro might also be due to the effect of these agents on the active center of the enzymes. 

Moduiation of enzymatic activity Protein kinase C (PKC) " Protein kinase B (PKB) " Protein tyrosine phosphorylation Protein phosphatase 2A (PP2A) " Phospholipase A2 " " Cyclooxygenase 5-Lipoxygenase Glutathione S-transferase NADPH-oxidase ... 

Samuelsson, B, Rouzer, CA and Matsumoto, T (1987b) Human leukocyte 5-lipoxygenase an enzyme possessing dual enzymatic activities and a multicomponent regulatory system. J Adv Prostaglandin Thromboxane LeukotRes, 17A, 1-11. 

In view of their reduction potential, flavonoids have also been shown to interact with enzymes either unspecifically or specifically and modify their activity through reduction of metals in the active center. Of particular interest, because of their role in inflammatory conditions, is the reductive inactivation of lipoxygenases, cyclo-oxygenases, myeloperoxidase, and xanthine oxidase. In view of prooxidant activity of the enzymes, their inhibition by polyphenols may be regarded as an indirect antioxidation action. The list of enzymatic activities inhibited by flavonoids and other polyphenols also include phospholipase A2, protein kinases, metalloproteinases, drug metabolism enzymes, and telomerase, as reviewed elsewhere (Frade et al, 2005). 

Enzymatically active materials (fruits, vegetables and some fats) contain a large number of other aldehydes that are produced from essential fatty acids, mainly linoleic and Knolenic acids (Table 8.9) by oxidation reactions catalysed by lipoxygenases. In some vegetables (e.g. in cucumbers), aldehydes also result from a-oxidation of fatty acids (Figure 8.15). The primary oxidation products of essential fatty acids are hydroperoxides, which break down to aldehydes and other products under the action of lyases and can be... 

Cellular lipoxygenases have been implicated as possible enzymatic mediators of endothelial cell-dependent oxidation of LDL. Inhibitors of lipoxygenase, but not cyclooxygenase, have been shown to be effective inhibitors of LDL oxidation using rabbit endothelial cells (Parthasarathy etal., 1989). Interestingly, a phospholipase A2 activity intrinsic to apo-B has also been implicated in the endothelial cell-dependent modification of LDL (Parthasarathay et al., 1985). 

Furthermore, in the system with coupled lipase and lipoxygenase, the production rate of HP is governed by the first enzymatic reaction and mass transfer. When TL,- is small (0 to 1 mM equiv. 3 mM LA), the kinetic curve has a sigmoid shape due to surface active properties of LA and HP [25]. Hydrolysis of TL and the increase of LA favor the transfer of LA. Such a transfer allows the lipoxygenase reaction to progress. Since lipox-ygenation consumes LA and produces HP, catalysis and transfer demonstrates a reciprocal influence. 

Leukotrienes (LTA, LTB LTC, LTD, and LTE ) are synthesized from arachi-donic acid by a cascade of enzymes that include 5-lipoxygenase (5-LOX), 5-lipoxy-genase-activating protein (FLAP), and leukotriene C4 synthase (LTC synthase) (79,80). The leukotriene LTA is synthesized by 5-LOX in the first step and is an unstable precursor that is then enzymatically converted to LTB or LTC (80,81), which can subsequently be metabolized to LTD and LTE. LTC, LTD, and LTE are the components of the slow-reacting substance of anaphylaxis. These moieties, particularly LTC and LTD, are active forms of CysLTs that interact with the G protein-coupled cysteinyl leukotriene receptors (CysLtrl and CysLtr2) (70,81,82). Once engaged, the activated CysLtrs receptors stimulate the secretion of mucus and induce edema and bronchoconstriction (81). 

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