Oxygenase lipoxygenase

Timegadine, a guanidine derivative, inhibits cyclo-oxygenase, lipoxygenase, and phospholipase activity. Reported adverse effects are skin rashes, oral lesions, epigastric pain, nausea, dysuria, dizziness, vertigo, and sleep disturbances. Liver enzyme changes and pneumonitis have also been described (1-4). 

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

Free radicals are essential to many normal biological processes. They are involved in cyclo-oxygenase and lipoxygenase action in eicosanoid... 

Figure 3 Illustration of possible partial reaction cycles of some oxygenase enzymes. Water molecules and protein ligands have sometimes been omitted for clarity, (a) P450 (18) (b) intradiol dioxygenase (7) (c) lipoxygenase (7) (d) a-KG-dependent non-heme Iron enzymes (14) (e) soluble methane monooxygenase (15) (f) uncoupled blnuclear copper (16) (g) coupled blnuclear copper (h) flavin monooxygenases (17).

Arachidonic acid is of particular importance, being the initial compound for eicosanoid biosynthesis. Prostaglandins, prostacyclins and thromboxanes are synthesized from the eicosanoids via the cyclo-oxygenase pathway. The important mediators of inflammation — such as leukotrienes and leukotetraenes — are synthesized via the lipoxygenase pathway, (s. fig. 3.10)... 

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... 

Interestingly, even at that time, a series of five histidine residues was postulated to constitute the potential iron-binding site, in that they are also conserved in other lipoxygenases, although site-specific mutagenesis studies indicated that three of these could be mutated individually in 5-LO without loss of either oxygenase or LTA4 synthetase activity (112,113). This proposal has now been refined and it is believed that the nonheme iron is bound permanently by and... 

Many of the biological actions of essential fatty acids are the result of their metabolic products, the eicosanoids. These are oxidized derivatives of AA and include prostaglandins and thromboxanes that are formed via the cyclo-oxygenase (COX) pathway, as well as hydroxy fatty acids and leukotrienes that arise by means of the lipoxygenase pathway. Another series of AA-derived products, the epoxy fatty acids, are produced by the cytochrome P450 epoxygenase pathway. The AA that serves as precursor for these reactions... 

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