Leukotriene Analysis Service

Leukotrienes (LTs) are a group of inflammatory lipid mediators derived from arachidonic acid (AA) via the 5-lipoxygenase (5-LOX) pathway. A characteristic feature of LTs is that they are produced by leukocytes and share a conjugated triene structure. LTs consist of cysteinylleukotrienes (CysLTs) and leukotriene B4 (LTB₄). CysLTs contain a cysteine ring, whereas LTB₄ is a noncysteine containing dihydroxy-leukotriene. The subtypes of CysLTs include leukotriene C4 (LTC₄), leukotriene D4 (LTD₄), and leukotriene E4 (LTE₄). The biological properties of LTs suggest that CysLTs play a crucial role in the pathogenesis of asthma. Currently, three CysLT₁ antagonists are commercially available: Pranlukast, Zafirlukast, and Montelukast. BLT antagonists, specific regulators of LTB₄, are still under clinical development.

 

LTs are derived from AA. They are rapidly produced at inflammation sites through a series of reactions initiated by cytosolic PLA₂(cPLA₂), releasing AA from nuclear membrane phospholipids. AA binds to the 5-lipoxygenase activating protein (FLAP) and is subsequently acted upon by 5-lipoxygenase (5-LO). The active site of 5-LO contains non-heme iron, transitioning from divalent to trivalent during catalysis. 5-LO, in conjunction with molecular oxygen, converts FLAP-bound AA to 5-hydroperoxy eicosatetraenoic acid (5-HPETE), forming the unstable and short-lived intermediate LTA₄. LTA₄ is converted to LTB₄ by the cytosolic enzyme LTA₄ hydrolase. Inflammatory cells with complete membrane protein LTC₄ synthase, such as eosinophils, basophils, mast cells, and alveolar macrophages, can synthesize CysLTs in response to biological and non-biological stimuli. LTC₄ synthase conjugates reduced glutathione at the C6 position of LTA₄ to form LTC₄. LTC₄ synthase is also associated with FLAP in a multi-molecular complex. Both LTB₄ and LTC₄ are transported to the extracellular space via transport proteins. Once transported, LTC₄ is rapidly cleaved by transpeptidase to produce LTD₄, which is finally converted to LTE₄ by dipeptidase through the removal of glycine.

 

LTs primarily act on subclasses of G-protein coupled receptors and may also act on peroxisome proliferator-activated receptors. LTs are involved in asthmatic and allergic reactions and play a role in maintaining the inflammatory response. Certain leukotriene receptor antagonists, such as montelukast and zafirlukast, are used to treat asthma. LTs also play a critical role in the inflammatory response. Certain LTs, such as LTB₄, have chemotactic effects on neutrophil migration, aiding in the recruitment of necessary cells into tissues. They also have potent effects on bronchoconstriction and can increase vascular permeability.

 

MtoZ Biolabs offers reliable, rapid, and cost-effective leukotriene analysis services and utilizes advanced LC-MS/MS systems for high stability, reproducibility, and sensitivity in its separation, characterization, identification, and quantification.

 

MtoZ Biolabs targeted LC-MS/MS can provide analysis of the following leukotriene compounds

1. LTC₄

2. LTD₄

3. LTE₄

4. LTB₄

5. 6-trans-LTB₄

6. 6-trans-12-epi-LTB₄

7. 20-Hydroxy-LTB₄

8. 20-Carboxy-LTB₄