Lipoxygenase

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Lipoxygenases LOXs catalyze the stereo-specific peroxidation of polyunsaturated fatty acids PUFAs to their corresponding hydroperoxy derivatives. ALOX15, which was first described in , has been extensively characterized and its biological functions have been investigated in a number of cellular systems and animal models. In macrophages, ALOX15 functions to generate specific phospholipid PL oxidation products crucial for orchestrating the nonimmunogenic removal of apoptotic cells ACs as well as synthesizing precursor lipids required for production of specialized pro-resolving mediators SPMs that facilitate inflammation resolution. Although its enzymatic properties are well described, the biological functions of ALOX15B are not fully understood. Lipoxygenases LOXs are non-heme iron-containing dioxygenases that catalyze the stereo-specific peroxidation of polyunsaturated fatty acids PUFAs containing one or more 1,4- cis , cis pentadiene moieties to the corresponding hydroperoxy derivatives Kuhn et al. In mammals, LOX enzymes are expressed in numerous cell types including epithelial, endothelial, and immune cells and are involved in various functions including skin barrier formation, cell differentiation, and immunity Kuhn et al. All mammalian LOXs are single polypeptide chain proteins that fold into a two-domain structure Kuhn et al.

Lipoxygenase

Federal government websites often end in. The site is secure. Lipoxygenases LOXs are dioxygenases that catalyze the formation of corresponding hydroperoxides from polyunsaturated fatty acids such as linoleic acid and arachidonic acid. LOX enzymes are expressed in immune, epithelial, and tumor cells that display a variety of physiological functions, including inflammation, skin disorder, and tumorigenesis. In the humans and mice, six LOX isoforms have been known. Many mutations in this isoform are found in epithelial cancers, suggesting a potential link between LOX and tumorigenesis. Defects in this gene result in ichthyosis, a cutaneous disorder characterized by pathophysiologically dried skin due to abnormal loss of water from its epithelial cell layer. Similarly, eLOX-3, which is also expressed in the skin epithelial cells acting downstream 12R-LOX, is another causative factor for ichthyosis. This isoform causes the constriction of bronchioles in response to cysteinyl leukotrienes such as LTC 4 , thus leading to asthma. It also induces neutrophilic inflammation by its recruitment in response to LTB 4. Currently, pharmacological drugs targeting FLAP are actively developing. This review summarized these functions of LOX enzymes under pathophysiological conditions in mammals. Lipoxygenases LOXs catalyze the oxygenation of polyunsaturated fatty acids such as arachidonic acid and linoleic acid [1,2]. The oxygenated lipids initiate subsequent biological reactions, activate cellular signaling mechanisms through specific cell surface receptors, or are further metabolized into potent lipid mediators.

Targeting biosynthetic networks of the proinflammatory and proresolving lipoxygenase metabolome. Table 1 Human lipoxygenase genes and their murine orthologs, lipoxygenase. Acknowledgment We thank Professor Emeritus Etsuo Niki of the University of Tokyo for suggesting the importance of the study of resolvins mentioned in this article.

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human Hs , mouse Mm and rat Rn. Show » « Hide. The lipoxygenases LOXs are a structurally related family of non-heme iron dioxygenases that function in the production, and in some cases metabolism, of fatty acid hydroperoxides. In humans there are five lipoxygenases, the 5S- arachidonate : oxygen 5-oxidoreductase , 12R- arachidonate lipoxygenase, 12R-type , 12S- arachidonate : oxygen oxidoreductase , and two distinct 15S- arachidonate : oxygen oxidoreductase LOXs that oxygenate arachidonic acid in different positions along the carbon chain and form the corresponding 5S-, 12S-, 12R-, or 15S-hydroperoxides, respectively.

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Lipoxygenases LOXs are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. Many studies have demonstrated that LOXs and their eicosanoid metabolite hydroxyeicosatetraenoate HETE , have significant pathological implications in inflammatory diseases. Increased level of LOX activity promotes stress both oxidative and endoplasmic reticulum -mediated inflammation, leading to damage in these tissues. In this article, we review the role of LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role. Inflammation is a conserved mechanism that serves as a defense against injurious stimuli, including invasion of pathogens, tissue injury, and intracellular damage signals [ 1 ]. Cells release a variety of factors, including histamines, prostaglandins, and bradykinin.

Lipoxygenase

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism.

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Irvin C. Ovarian cancer risk associated with inherited inflammation-related variants. Tintinger G. Young R. Macrophages: development and tissue specialization. Schematic diagram of the three-dimensional structure of soybean Glycine max lipoxygenase-1, showing the small N-terminal domain I and the large C-terminal domain II. Lipids of human atherosclerotic plaques and xanthomas: clues to the mechanism of plaque progression. References 1. Jack, G. Cold Spring Harb. Nordihydroguaiaretic acid NDGA , which is a well-known antioxidant, inhibits platelet lipoxygenase and lipoxygenase [ 75 ].

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Many mutations in this isoform are found in epithelial cancers, suggesting a potential link between LOX and tumorigenesis. Via M. Stereochemistry and mechanism of the biosynthesis of leukotriene A4 from 5 S -hydroperoxy-6 E ,8,11,14 Z -eicosatetraenoic acid. Antileukotriene agents in asthma: The dart that kills the elephant? Mice infected with the helminth Nippostrongylus brasiliensis develop substantial lung tissue damage followed by a rapid IL-4 and IL response, which is critical for resolution of inflammation and tissue repair. Ohgami R. The molecular biology of mammalian lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient mice. In human monocyte-derived macrophages, ALOX15 expression is strictly cytokine-dependent and is strongly up-regulated following stimulation with IL-4 or IL Conrad et al. Shen, J. There are a limited number of studies involving Alox15b. Evidence that Sp1 positively and Sp3 negatively regulate and androgen does not directly regulate functional tumor suppressor lipoxygenase 2 LOX2 gene expression in normal human prostate epithelial cells. The identification of the role of arachidonic acid metabolites in several inflammatory diseases led to a significant drug discovery effort around arachidonic acid metabolizing enzymes. Leedom A. Iron-Chelator Inhibitors In general a non-heme iron atom in lipoxygenases coordinates with amino acid residues and a water molecule forming an octahedral complex [ 90 ].