数据之源，洞见之始

Metabolite Card

Note

11-trans-Leukotriene C4 (11-trans-LTC4) is a leukotriene derivative formed by the metabolism of LTA4 and is found in human endothelial cells. Leukotrienes (LT) are a family of naturally occurring lipids that are oxygenated metabolites of arachidonic acid. Biosynthesis of the leukotrienes involves the action of a lipoxygenase on arachidonate to yield a hydroperoxy intermediate which is then dehydrated to the allylic epoxide, LTA4. LTA4 can be hydrolyzed to the dihydroxy acid, LTB4 or it can be conjugated with glutathione (GSH) to produce the parent slow reacting substance, LTC4. The leukotrienes are mediators of inflammation, hypersensitivity reactions, and respiratory disorders. On a cellular level, LTC4 and its metabolites, LTD4 and LTE4, are potent constrictors of vascular bronchial smooth muscle. LTC4 and LTD4 also induce plasma leakage from the microvasculature. LTB4 is a potent polymorphonuclear leukocyte (PMNL) chemotaxin and induces neutrophils to degranulate, generate superoxide, and adhere to vascular endothelium. Several investigations of leukotriene synthesis by blood vessels and cultured vascular cells have been undertaken. Vascular preparations have been shown to produce LTB4 and LTC4 and to metabolize LTC4 to LTD4 and LTE4. In addition, mast cells, macrophages, and PMNL, all of which may contaminate whole vessel preparations, are known to synthesize both peptide-containing and dihydroxy acid leukotrienes. Consequently, it is unclear what cells are contributing to vascular leukotriene synthesis. No evidence of isolated vascular cell leukotriene synthesis is currently available. Indeed, this report and others have been unable to detect endothelial cell conversion of arachidonic acid to the leukotrienes. The fact that vascular endothelium lacks the full complement of leukotriene biosynthetic enzymes does not preclude an active role for this tissue in leukotriene metabolism. In some cases, tissues which are not known to synthesize leukotrienes from arachidonate are able to catalyze one or more of the intermediate steps of the pathway. In the present investigation, the leukotriene metabolism of porcine aortic endothelium has been studied. Evidence is presented which indicates that endothelial cells are unable to convert arachidonic acid to LTC4 but, nevertheless, contain LTC4 synthetase. Additional experiments suggest that a neutrophil-endothelial cell interaction augments vascular LTC4 synthesis by the intercellular transfer of LTA4 from PMNL to endothelial cells (PMID: 3023351). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signalling pathways.