From LipidomicsWiki
Leukotrienes (LO) are eicosanoids produced in leukocytes and endothelial cells and have a triene structure (Samuelsson et al. 1979). Leukotrienes are final metabolites of 5-HPETE, derived from the conversion of AA by 5-lipoxygenase (5-LO), which is dehydrated to labile 5,6 epoxide intermediate LTA4. The LTA4 hydrolase converts LTA4 to biologically active LTB4, which in the presence of LTC4 synthase conjugates with reduced glutathione to LTC4. Removal of glutamic acid by glutamyl transpeptidase from LTC4 generates LTD4 and LTE4 results from subsequent cleavage of glycine by dipeptidase. LTC4 and its metabolites are known as cysteinyl leukotrienes (Khan et al. 2003). LTC4 synthase is a membrane protein, found in cells of hematopoietic origin (Lam, 2003).
- Leukotrienes are eicosanoids produced in leukocytes and endothelial cells and have a triene structure (Samuelsson et al. 1979).
- Leukotrienes are final metabolites of 5-HPETE, derived from the conversion of AA by 5-lipoxygenase (5-LO), which is dehydrated to labile 5,6 epoxide intermediate LTA4. The LTA4 hydrolase converts LTA4 to biologically active LTB4, which in the presence of LTC4 synthase conjugates with reduced glutathione to LTC4. Removal of glutamic acid by glutamyl transpeptidase from LTC4 generates LTD4 and LTE4 results from subsequent cleavage of glycine by dipeptidase. LTC4 and its metabolites are known as cysteinyl Leukotrienes (Khan et al. 2003).
- LTC4 synthase is a membrane protein, found in cells of hematopoietic origin (Lam, 2003).
LTB4 and cysteinyl leukotrienes signal through receptors, which are member of the G protein-coupled receptor superfamily. LTC4, LTD4 and LTE4 bind to CysLT1 and CysLT2 receptors to exert their biological effects. The production of LTB4 from endogenous but not from exogenous sources requires the presence of 5-LO activating protein (FLAP) (Dixon et al. 1990). FLAP and leukotriene C4 synthase and also prostaglandin E synthase belong to membrane-associated proteins in eicosanoid and glutathione metabolism superfamily (MAPEG) (Bresell et al. 2005).
LTB4 increases vascular permeability, induces the release of lysosomal enzymes, is potent leukocyte chemoatractant and enhances generation of reactive oxygen species and production of proinflammatory cytokines like TNFα, IL-1 and IL-6 (Calder, 2005).
LTC4, LTD4 and LTE4 are among the most potent bronchoconstrictors; additionally they exert mitogenic effects, modify vascular integrity and play a pathological role in asthma (Silverman et al. 1998).
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