Eicosanoid Metabolism Pathway

Preferred Label : Eicosanoid Metabolism Pathway;

NCIt related terms : Eicosanoid Metabolism;

Alternative definition : BIOCARTA: The eicosanoids are a family of lipophilic hormones derived from the twenty carbon fatty acid arachidonic acid. Although they are diverse in structure, many eicosanoids have roles in inflammation, including regulation of vasodilation, vascular permeability, pain, and recruitment of leukocytes. Most members of this family are rapidly metabolized near their site of synthesis, so they act locally on neighboring cells, not distant parts of the body. They are also not stored in cells, but synthesized rapidly in response to stimuli, making regulation of their synthesis a key to their activity. Many drugs act through modulating the production of eicosanoids or modulating their signaling pathways. Hormones in the eicosanoid family include the prostaglandins, thromboxanes, leukotrienes, and prostacyclins. The first step in the production of eicosanoids is the release of arachidonic acid from either diacylglycerol or phospholipids by membrane bound phospholipases in response to extracellular stimulus. Arachidonic acid has several possible fates, including oxygenation by lipoxygenases to make HPETEs (hydroperoxyeicosatetraenoic acids), or production of prostaglandin H2 by PGH2 synthase. 5-lipoxygenase acts with the membrane bound protein FLAP (five lipoxygenase activating protein) to produce the epoxide leukotriene LTA4 which is hydrolyzed to produce LTB4 or has glutathione added by a glutathione S-transferase to produce LTC4 and LTD4. A G-protein coupled receptor for LTD4, CysLT1, mediates an important component of the inflammatory response of leukotrienes on airway constriction and recruitment of leukocytes, and several marketed asthma drugs act as antagonists of the CysLT1 receptor. PGH2 synthase actually consists of two enzyme components, a cyclooxygenase and a peroxidase, and there are more than one type of cyclooxygenase, including Cox-1 and Cox-2. Recent NSAIDS acting selectively as Cox-2 inhibitors like Vioxx are widely used for the treatment of arthritis and other inflammatory conditions, inhibiting the production of downstream thromboxanes and prostaglandins. PGH2 also has several possible fates, including conversion by thromboxane synthase to Tpx2, an eicosanoid with potent coagulation and vasoconstriction activity. PGI2, or prostacyclin, synthesized by prostacyclin synthase, has properties opposite those of thromboxane, causing vasodilation and a reduction in clotting through the IP receptor, causing thromboxanes and PGI2 to act in opposition to each other. Thromboxane antagonists and prostacyclin agonists both provide tools and drugs to reduce vasoconstriction. The prostaglandins include PGD2, PGE2 and PGF2, with varying degrees of selectivity among their receptors, DP, EP and FP, respectively. PGE2 exerts biological effects including induction of pain, fever and vasodilation through at least four receptors, EP1, EP2, EP3 and EP4, and EP3 is found in multiple splice variants. The diversity of the eicosanoids and their receptors and their involvement in many disease states makes it likely that this pathway will continue as a major research focus. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_eicosanoidPathway;

Details

Origin ID

C39060;

UMLS CUI

C1522543;

Automatic exact mappings (from CISMeF team)
- icosanoid metabolic process [GO term]
Semantic type(s)
- Functional Concept [UMLS semantic type]
has_gene_product_element
- Cysteinyl Leukotriene Receptor 2 [NCIt concept]
- Cytosolic Phospholipase A2 [NCIt concept]
- Phospholipase A2 [NCIt concept]
- Prostacyclin Synthase [NCIt concept]
- Prostaglandin E Synthase [NCIt concept]
- Prostaglandin E2 Receptor EP4 Subtype [NCIt concept]
- Thromboxane A2 Receptor [NCIt concept]
pathway_has_gene_element
- CYSLTR2 wt Allele [NCIt concept]
- PLA2G1B wt Allele [NCIt concept]
- PLA2G4A wt Allele [NCIt concept]
- PTGER4 wt Allele [NCIt concept]
- PTGES wt Allele [NCIt concept]
- PTGIS wt Allele [NCIt concept]
- TBXA2R wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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