• enzymes
  • 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. (wikipedia.org)
  • Based on detailed analyses of 15-lipoxygenase 1 and stabilized 5-lipoxygenase, lipoxygenase structures consist of a 15 kilodalton N-terminal beta barrel domain, a small (e.g. ~0.6 kilodalton) linker inter-domain (see protein domain#Domains and protein flexibility), and a relatively large C-terminal catalytic domain which contains the non-heme iron critical for the enzymes' catalytic activity. (wikipedia.org)
  • predominantly
  • Based predominantly on the presence of its mRNA, human ALOX12 is distributed predominantly in blood platelets and leukocytes and at lower levels in the basal layer of the epidermis (particularly in the skin lesions of psoriasis), islets of Langerhans within the pancreas, and certain cancers. (wikipedia.org)
  • acid
  • The former product was further converted to 14,15-epoxy acid. (nii.ac.jp)
  • 12-Hydroxyeicosatetraenoic acid (12-HETE) is a derivative of the 20 carbon polyunsaturated fatty acid, arachidonic acid, containing a Hydroxyl residue at carbon 12 and a 5Z,8Z,10E,14Z Cis-trans isomerism configuration (Z=cis, E=trans) in its four double bonds. (wikipedia.org)
  • It was first found as a product of arachidonic acid metabolism made by human and bovine platelets through their 12S-lipoxygenase (i.e. (wikipedia.org)
  • 12(R)-HpETE also spontaneously decomposes to a mixture of hepoxilins and trihydroxy-eicosatetraenoic acids that possess R or S hydroxy and epoxy residues at various sites while 8R-hydroxy,11R,12R-epoxy-hepoxilin A3 spontaneously decomposes to 8R,11R,12R-trihydroxy-5Z,9E,14Z-eicosatetraenoic acid. (wikipedia.org)
  • see 15-Hydroxyeicosatetraenoic acid). (wikipedia.org)
  • 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (12(R)-HpETE), a product with very different pathophysiological roles than that of 12(S)-HpETE (see ALOX12B). (wikipedia.org)
  • 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15(S)-HpETE): Eoxin A4 Eoxin C4 Eoxin D4 Eoxin E4 A 15-lipoxygenase (i.e. (wikipedia.org)
  • 15-(S)-HpETE is then metabolized to 14(R)-glutothionyl-15(S)hydroxy-5Z,8Z,10E,13E-eicosatetraenoic acid (i.e. (wikipedia.org)
  • The eoxin-forming pathway sequence is as follows: Arachidonic acid15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HPETE)) via 15-LOX-1 or possibly 15-LOX-2, i.e. (wikipedia.org)
  • whereas esterified arachidonic acid is primarily metabolized by 15-LOX-1. (mdpi.com)
  • Its 15(R) enantiomer is designated 15(R)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid. (wikipedia.org)
  • Both stereoisomers are produced from their corresponding S and R 15-HpETE stereoisomers, i.e. 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE) and (15R)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(R)-HpETE). (wikipedia.org)
  • The freed arachidonic acid is then converted to 15-hydroperoxy/hydroxy products by one or more of the following five pathways. (wikipedia.org)
  • The PUFA precursors to the eicosanoids include: Arachidonic acid (AA), i.e. 5Z, 8Z,11Z,14Z-eicosatetraenoic acid is ω-6 fatty acid, with four double bonds in the cis configuration (see Cis-trans isomerism) each located between carbons 5-6, 8-9, 11,-12, and 14-15. (wikipedia.org)
  • Dihomo-gamma-linolenic acid (DGLA), 8Z, 11Z,14Z-eicosatrienoic acid is an ω-6 fatty acid with three cis double bonds, each located between carbons 8-9, 11,-12, and 14-15. (wikipedia.org)
  • while the third domain of terrestrial life, the archaea, possesses proteins with a slight (~20%) amino acid sequence similarity to lipoxygenases, these proteins lack iron-binding residues and therefore are not projected to possess lipoxygenase activity. (wikipedia.org)
  • Certain types of the lipoxygenases, e.g. human and marine 15-lipoxygenase 1, 12-lipoxygenase B, and ALOXE3, are capable of metabolizing fatty acid substrates that are constituents of phospholipids, cholesterol esters, or complex lipids of the skin. (wikipedia.org)
  • pathways
  • In addition, cells, when so activated, may transfer their released polyunsaturated fatty acids to adjacent or nearby cells which then metabolize them through their lipoxygenase pathways in a process termed transcellular metabolism or transcellular biosynthesis. (wikipedia.org)
  • LOXs
  • 4,5 Lipoxygenases (LOXs) are nonheme iron dioxygenases that stereospecifically introduce molecular oxygen into polyunsaturated fatty acids (PUFA) such as AA, resulting in the formation of hydroperoxyeicosatetraenoic acids (HPETEs) which are further converted to hydroxyeicosatetraenoic acids (HETEs). (ahajournals.org)
  • derivatives
  • Thus, 15(S)-HETE and 15(S)-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives. (wikipedia.org)
  • Mice
  • Indeed, mice made deficient of 12/15-lipooxygenase exhibit an attenuated allergic airway inflammation response compared to wild type control mice. (wikipedia.org)
  • respectively
  • The initial 12(S)-HpETE and 12(R)-HpETE products, regardless of their pathway of formation, are rapidly reduced to 12(S)-HETE and 12(R)-HETE, respectively, by ubiquitous cellular peroxidases, including in particular Glutathione peroxidases or, alternatively, are further metabolized as described below. (wikipedia.org)
  • 15(S)-HETE induced expression and secretion of interleukin-6 (IL-6), as analyzed by RT-PCR and ELISA, respectively. (ahajournals.org)
  • hydroperoxide
  • This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15(S)-HETE. (wikipedia.org)
  • Plant lipoxygenase in conjunction with hydroperoxide lyases are responsible for many fragrances and other signalling compounds. (wikipedia.org)
  • product
  • 10,11 It was also demonstrated that atherosclerotic arteries express increased levels of 15-LOX1 and its AA product, 15-HETE in rabbits. (ahajournals.org)
  • cells
  • 3) 12-Lipoxygenase of human uterine cervix : Nigam's group of Free University of Berlin had found that human uterine cervix had 12-lipoxygenase activity which was lower in cancer cells. (nii.ac.jp)
  • it also promotes the malignant behavior of cultured human cancer cells as well as the growth of certain cancers in animal models (see 12-HETE). (wikipedia.org)
  • Eoxins have been suggested to contribute to inflammation in airway allergies and the development and/or progression of certain types of cancers, particularly Hodgkin's lymphoma (a cancer originating from white blood cells), prostate cancer, and colon carcinoma. (wikipedia.org)
  • Cells and tissues rich in 15-LOX-1 activity such as human eosinophils, umbilical cord-derived mast cells, nasal polyps from allergic subjects, airway epitheleal cells, and L1236 Reed-Sternberg cells derived from Hodgkin's Disease tumors produce eoxins. (wikipedia.org)
  • lacking 15-LOX-1, it is assumed that these cells employ 12/15-lipoxygenase to initiate this synthesis. (wikipedia.org)
  • 12,13 In addition, recently LOX products of PUFA have also been shown to be potent chemoattractants for residential and invading immune cells recruited to lesion areas. (ahajournals.org)
  • activity
  • Last November Natsuo Ueda visited Free University in Berlin and confirmed the 12-lipoxygenase activity in human uterine cervix. (nii.ac.jp)
  • 15(R)-HpETE and 15(R)-HETE lack some of the activity attributed to their S stereoisomers but can be further to metabolized to bioactive products viz. (wikipedia.org)
  • The lipoxygenases are related to each other based upon their similar genetic structure and dioxygenation activity. (wikipedia.org)
  • chirality
  • In this terminology S refers to the absolute configuration of the chirality of the hydroxy functional group at carbon position 15. (wikipedia.org)
  • protein
  • 15 This transcription factor is activated by phosphorylation of Ser133 residue, which is typically performed by protein kinase A. 16 However, other protein kinases such as extracellular signal-regulated kinases 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), calmodulin kinase (CaMK), and protein kinase B (PKB) have also been shown to phosphorylate and activate CREB. (ahajournals.org)
  • 15,17 CREB forms homo- or heterodimers with members of either the CREB/activating transcriptional factor (ATF) or the activator protein-1 (AP-1) family of transcriptional factors. (ahajournals.org)