Leukotrienes (LTs) are a group of inflammatory mediators derived from arachidonic acid (AA) through the 5-lipoxygenase (5-LOX) pathway. A notable characteristic of leukotrienes is that they are produced by leukocytes and share a conjugated triene structure. Leukotrienes consist of cysteinyl leukotrienes (CysLTs) and leukotriene B4 (LTB4). CysLTs contain a cysteine ring, whereas LTB4 is a non-cysteine leukotriene that contains dihydroxy groups. Subtypes of CysLTs include leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4). The biological properties of leukotrienes indicate that CysLTs play an important role in the pathogenesis of asthma. Currently, there are three CysLT1 antagonists available on the market: pranlukast, zafirlukast, and montelukast. BLT antagonists, a specific type of LTB4 regulator, are still in clinical development.
Leukotrienes are derived from arachidonic acid, and these bioactive lipids are rapidly produced at sites of inflammation through a series of reactions initiated by cytosolic phospholipase A2 (cPLA2), which releases arachidonic acid from phospholipids in the nuclear membrane. Arachidonic acid binds to 5-lipoxygenase-activating protein (FLAP) and is further utilized by 5-lipoxygenase (5-LO). The active site of 5-lipoxygenase contains non-heme iron, which transitions from a divalent to a trivalent state during the catalytic process. 5-lipoxygenase acts with molecular oxygen on arachidonic acid bound to FLAP, forming 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and subsequently an unstable, short-lived intermediate, LTA4. LTA4 is converted to LTB4 by cytosolic enzyme LTA4 hydrolase. Inflammatory cells with intact membrane protein LTC4 synthase, such as eosinophils, basophils, mast cells, and alveolar macrophages, can synthesize CysLTs in response to biotic and abiotic stimuli. LTC4 synthase conjugates reduced glutathione to the C6 position of LTA4, forming LTC4. LTC4 synthase is also associated with FLAP in a multi-molecular complex. Both LTB4 and LTC4 are exported to the extracellular space via transport proteins. Once exported, LTC4 is rapidly cleaved by gamma-glutamyl transpeptidase to produce LTD4, which is then converted to LTE4 by dipeptidase removal of glycine.
Leukotriene Analysis
Leukotrienes primarily act on subclasses of G-protein-coupled receptors and may also act on peroxisome proliferator-activated receptors. Leukotrienes are involved in asthma and allergic reactions and play a role in maintaining the inflammatory response. Certain leukotriene receptor antagonists, such as montelukast and zafirlukast, can be used to treat asthma. Leukotrienes also play an important role in the inflammatory response. Some leukotrienes, like LTB4, have a chemotactic effect on neutrophil migration, helping to bring necessary cells into tissues. They also have a strong effect on bronchoconstriction and can increase vascular permeability.
BioTekPark Biotechnology provides reliable, fast, and cost-effective leukotriene analysis services based on a highly stable, reproducible, and sensitive system for separation, characterization, identification, and quantitative analysis, combined with LC-MS/MS.
BioTekPark targeted LC-MS/MS can provide analysis of the following leukotriene compounds
