EXC4
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EXC4
Eoxin C4, also known as 14,15-leukotriene C4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(''S'')-hydroperoxyeicosapentaenoic acid (i.e. 15(''S'')-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e. LTA4, LTC4, LTD4, and LTE4. This pathway is schematically shown as follows: EXA4 is viewed as an intracellular-bound, short-lived intermediate which is rapidly metabolized to the down-stream eoxins. The eoxins down stream of EXA4 are secreted from their parent cells and, it is proposed but not yet proven, serve to regulate allergic responses and the development of certain cancers (see Eoxins Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds th ...
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Eoxins
Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds that regulate inflammatory and immune responses). They are produced by human eosinophils (a class of white blood cells), mast cells, the L1236 Reed–Sternberg cell line derived from Hodgkin's lymphoma, and certain other tissues. These cells produce the eoxins by initially metabolizing arachidonic acid, an omega-6 (ω-6) fatty acid, via any enzyme possessing 15-lipoxygenase activity. The product of this initial metabolic step, 15(S)-hydroperoxyeicosatetraenoic acid, is then converted to a series of eoxins by the same enzymes that metabolize the 5-lipoxygenase product of arachidonic acid metabolism, i.e. 5-Hydroperoxy-eicosatetraenoic acid to a series of leukotrienes. That is, the eoxins are 14,15-disubstituted analogs of the 5,6-disubstituted leukotrienes. A closely related set of 15-lipoxygenase metabolites are derived from anandamide (i.e. arachidonic acid containing ethanolamine esterified ...
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Eoxin
Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds that regulate inflammatory and immune responses). They are produced by human eosinophils (a class of white blood cells), mast cells, the L1236 Reed–Sternberg cell line derived from Hodgkin's lymphoma, and certain other tissues. These cells produce the eoxins by initially metabolizing arachidonic acid, an omega-6 (ω-6) fatty acid, via any enzyme possessing 15-lipoxygenase activity. The product of this initial metabolic step, 15(S)-hydroperoxyeicosatetraenoic acid, is then converted to a series of eoxins by the same enzymes that metabolize the 5-lipoxygenase product of arachidonic acid metabolism, i.e. 5-Hydroperoxy-eicosatetraenoic acid to a series of leukotrienes. That is, the eoxins are 14,15-disubstituted analogs of the 5,6-disubstituted leukotrienes. A closely related set of 15-lipoxygenase metabolites are derived from anandamide (i.e. arachidonic acid containing ethanolamine esterified ...
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EXA4
Eoxin A4, also known as 14,15-leukotriene A4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(''S'')-hydroperoxyeicosapentaenoic acid (i.e. 15(''S'')-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e. LTA4, LTC4, LTD4, and LTE4. This pathway is schematically shown as follows: EXA4 is viewed as an intracellular-bound, short-lived intermediate which is rapidly metabolized to the down-stream eoxins. The eoxins down stream of EXA4 are secreted from their parent cells and, it is proposed but not yet proven, serve to regulate allergic responses and the development of certain cancers (see Eoxins Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds th ...
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EXD4
Eoxin D4, also known as 14,15-leukotriene D4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(''S'')-hydroperoxyeicosapentaenoic acid (i.e. 15(''S'')-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e. LTA4, LTC4, LTD4, and LTE4. This pathway is schematically shown as follows: EXA4 is viewed as an intracellular-bound, short-lived intermediate which is rapidly metabolized to the down-stream eoxins. The eoxins down stream of EXA4 are secreted from their parent cells and, it is proposed but not yet proven, serve to regulate allergic responses and the development of certain cancers (see Eoxins Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds th ...
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EXE4
Eoxin E4, also known as 14,15-leukotriene E4, is an eoxin. Cells make eoxins by metabolizing arachidonic acid with a 15-lipoxygenase enzyme to form 15(''S'')-hydroperoxyeicosapentaenoic acid (i.e. 15(''S'')-HpETE). This product is then converted serially to eoxin A4 (i.e. EXA4), EXC4, EXD4, and EXE4 by LTC4 synthase, an unidentified gamma-glutamyltransferase, and an unidentified dipeptidase, respectively, in a pathway which appears similar if not identical to the pathway which forms leukotreines, i.e. LTA4, LTC4, LTD4, and LTE4. This pathway is schematically shown as follows: EXA4 is viewed as an intracellular-bound, short-lived intermediate which is rapidly metabolized to the down-stream eoxins. The eoxins down stream of EXA4 are secreted from their parent cells and, it is proposed but not yet proven, serve to regulate allergic responses and the development of certain cancers (see Eoxins Eoxins are proposed to be a family of proinflammatory eicosanoids (signaling compounds th ...
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Leukotriene C4
Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), Arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate. The MRP1 transporter then secretes cytosolic LTC4 and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD4 and LTE4. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction. In cells of non-haematopoietic lineage, endoplasmic reticulum (ER) stress and chemotherapy induce LTC4 biosynthesi ...
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15-lipoxygenase
ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically important products. ▼ Gene Function Kelavkar and Badr (1999) stated that the ALOX15 gene product is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. Kelavkar and Badr (1999) described experiments yielding data that supported the hypothesis that loss of the TP53 gene, or gain-of-function activities resulting from the expression of its mutant forms, regulates ALOX15 promoter activity in human and in mouse, albeit in directionally opposite manners. These studies defined a direct link between ALOX15 gene activity and an established tumor-suppressor gene located in close chromosomal proximity. Kelavkar and Badr (1999) referred to this as evidence that 15-lipoxygenase is a mutator gene. ▼ Mapping By PCR anal ...
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15-Hydroxyeicosatetraenoic Acid
15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15(''S'')-HETE, and 15''S''-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15(''S'')-hydroperoxyeicosatetraenoic acid (15(''S'')-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15''(S)''-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5''S'',15''S''-dihydroxy-eicosatetraenoic acid (5(''S''),15(''S'')-diHETE), 5-oxo-15(''S'')-hydroxyeicosatetraenoic acid (5-oxo-15(''S'')-HETE, a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15(''S'')-HETE and 15(''S'')-HpETE, in addition to having intrinsic biological activities, are key precursors to ...
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LTC4 Synthase
Leukotriene C4 synthase is an enzyme that in humans is encoded by the ''LTC4S'' gene. The protein encoded by this gene, LTC4S (or glutathione S-transferase II) is an enzyme that converts leukotriene A4 and glutathione to create leukotriene C4. This is a member of MAPEG family of transmembrane proteins. A trimer of Leukotriene C4 synthase is localized on the outer nuclear membrane and endoplasmic reticulum, where it forms a complex with 5-Lipoxygenase-activating protein. This protein is remotely related to microsomal glutathione S-transferase. Function The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family includes a number of human proteins, several of which are involved the production of leukotrienes. This gene encodes an enzyme that catalyzes the first step in the biosynthesis of cysteinyl leukotrienes, potent biological compounds derived from arachidonic acid. Leukotrienes have been implicated as mediators of anaphylaxis and inflammatory ...
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Gamma-glutamyltransferase
Gamma-glutamyltransferase (also γ-glutamyltransferase, GGT, gamma-GT, gamma-glutamyl transpeptidase; ) is a transferase (a type of enzyme) that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate). GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione as well as drug and xenobiotic detoxification. Other lines of evidence indicate that GGT can also exert a pro-oxidant role, with regulatory effects at various levels in cellular signal transduction and cellular pathophysiology. This transferase is found in many tissues, the most notable one being the liver, and has significance in medicine as a diagnostic marker. Nomenclature The name γ-glutamyltransferase is preferred by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. The Expert Panel on Enzymes of the In ...
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Dipeptidase
Dipeptidases are enzymes secreted by enterocytes into the small intestine. Dipeptidases hydrolyze bound pairs of amino acids, called dipeptides. Dipeptidases are secreted onto the brush border of the villi in the small intestine, where they cleave dipeptides into their two component amino acids prior to absorption. They are also found within the enterocytes themselves, performing cytosolic digestion of absorbed dipeptides. Dipeptidases are exopeptidases, classified under EC number 3.4.13. See also * Membrane dipeptidase Membrane dipeptidase (, ''renal dipeptidase'', ''dehydropeptidase I (DPH I)'', ''dipeptidase'', ''aminodipeptidase'', ''dipeptide hydrolase'', ''dipeptidyl hydrolase'', ''nonspecific dipeptidase'', ''glycosyl-phosphatidylinositol-anchored renal di ... References External links * Enzymes EC 3.4.13 {{enzyme-stub ...
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LTA4
Leukotriene A4 (LTA4) is a leukotriene, and is the precursor for the productions of LTB4 (leukotriene B)) and LTC4 (leukotriene C4). Biosynthesis of Leukotriene A4 Following the biosynthesis of eicosanoid, triggered as a result of infection or inflammation, the resulting arachidonic acid substrate is released from the cell membrane phospholipid will enter the lipooxygenase pathway to produce Leukotriene A4. In this pathway, arachidonic acid is converted into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) as a result of a catalytic complex consisting of the enzyme 5-lipoxygenase (5-LO) and FLAP (5-Lipoxygenase-activating protein) in the presence of ATP and Calcium ions. The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA4 which is quickly hydrolyzed by the LTA4H (Leukotriene A4 hydrolase) enzyme to produce LTB4, or synthesized by LTC4S (Leukotriene C4 synthase) with the addition of glutathione to produce LTC4 which can be further metabolized to produce LTD4 (Le ...
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