Lipoxygenase proteins

Figure 16.9 The PCET reaction catalyzed by soybean lipoxygenase. This reaction entails a net hydrogen atom transfer from the linoleic acid substrate to the Fe(lll)-OH cofactor. This conformation was obtained from docking calculations that included the entire soybean lipoxygenase protein. Reproduced from Ref [47].

On stimulation of rat alveolar macrophages with the calcium ionophore A-23187 (1 pM for 30 min), synthesis of leukotriene B4 increased with the degree of maturation, although it was diminished in the oldest subpopulation (Covin et al. 1998). This maturation-dependent upregulation was not explained by increases in arachidonic acid release but was associated with increased expression of 5-lipoxygenase protein as determined by immunoblot analysis. Whereas 5-lipoxygenase is primarily cyto-... 

Genes involved in the uptake and degradation of tocopherols - Genes implicated with lipid uptake and. Mi / °f J - Protein kinase C (PKC) - Cyclooxygenase - 5-Lipoxygenase - Cytokine release (IL-1P)... 

C. K., Sigal, E., Witztum, J.L. and Steinberg, D. (1990). Localisation of 15-lipoxygenase mRNA and protein with epitopes of oxidised low density lipoprotein in macrophrge rich areas of artherosderotic lesions. Proc. Natl Acad. Sci. USA 87, 6959-6963. 

Fe-TPAA Fe(III)-tris[N-(2-pyridylmethyl)-2-aminoethyl] amine Fe-TPEN Fe(II)-tetrakis-N,N,N, N -(2-pyridyl methyl-2-aminoethyl)amine FFA Free fatty acids FGF Fibroblast growth factor FID Flame ionization detector FITC Fluorescein isothiocyanate FKBP FK506-binding protein FLAP 5-lipoxygenase-activating protein... 

Zhuang H, Barth MM and Hildebrand DF. 1994. Packaging influenced total chlorophyll, soluble protein, fatty acid composition and lipoxygenase activity in broccoli florets. J Food Sci 59(6) 1171-1174. 

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

In contrast to numerous literature data, which indicate that protein oxidation, as a rule, precedes lipid peroxidation, Parinandi et al. [66] found that the modification of proteins in rat myocardial membranes exposed to prooxidants (ferrous ion/ascorbate, cupric ion/tert-butyl-hydroperoxide, linoleic acid hydroperoxide, and soybean lipoxygenase) accompanied lipid peroxidation initiated by these prooxidant systems. 

Soy beans are another crop that will not grow in Europe. The soy bean is used as a source of both protein and vegetable oil. Enzyme active soy flour has been used in bread since the 1930s. The flour contains a lipoxygenase system that assists with the development of the dough and slightly bleaches the bread. Soy flour is classed as an ingredient rather than an additive. 

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... 

Flavor is one of the major characteristics that restricts the use of legume flours and proteins in foods. Processing of soybeans, peas and other legumes often results in a wide variety of volatile compounds that contribute flavor notes, such as grassy, beany and rancid flavors. Many of the objectionable flavors come from oxidative deterioration of the unsaturated lipids. The lipoxygenase-catalyzed conversion of unsaturated fatty acids to hydroperoxides, followed by their degradation to volatile and non-volatile compounds, has been identified as one of the important sources of flavor and aroma components of fruits and vegetables. An enzyme-active system, such as raw pea flour, may have most of the necessary enzymes to produce short chain carbonyl compounds. 

Knapp, M.J., Rickert, K. and Khnman, J.P. (2002). Temperature-dependent isotope effects in soybean lipoxygenase-1 correlating hydrogen tunneling with protein dynamics. J. Am. Chem. Soc. 124, 3865-3874... 

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). 

Kedda MA, Worsley P, Shi J, Phelps S, Duffy D, Thompson PJ. (2005) Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population. Clin Exp Allergy. 35, 332-338. 

Ben-Asher E, Lancet D. (2004) 5-Lipoxygenase activating protein (ALOX5AP) association with cardiovascular infarction and stroke. Isr Med Assoc J. 6, 318-319. 

Finally there has been a growing interest in the development of selective leukotriene inhibitors. Bay Y 1015 (R-(-)-2-cycloheptyl-N-methylsulfonyl-(4-(2-quinolinyl-methoxy) phenyl)-acetamide) is a quinoline-type 5-lipoxygenase-activating protein inhibitor which was effective in inhibiting inflammation in a dextran sulfate model of mouse colitis [112]. Whether these compounds can also exert their anti-inflammatory action through inhibition of endothelial cell activation needs to be established. 

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