Leukotriene C4 synthase (LTC4S) (LTC4S)

Leukotriene C4 synthase (LTC4S) is a specialized integral membrane enzyme that catalyzes the final, committed step in the biosynthesis of cysteinyl leukotrienes (CysLTs). It facilitates the conjugation of the unstable intermediate leukotriene A4 (LTA4) with reduced glutathione to form leukotriene C4 (LTC4), a potent proinflammatory mediator (UniProt: Q16873). LTC4 and its derivatives, LTD4 and LTE4, are primary drivers of bronchoconstriction, airway edema, and mucus hypersecretion, making LTC4S a critical node in the pathogenesis of respiratory diseases such as asthma and aspirin-exacerbated respiratory disease (PubMed: 10661307, PubMed: 21169469). The enzyme belongs to the MAPEG family and is predominantly expressed in effector cells of the innate immune system, including mast cells and eosinophils. While clinical management of leukotriene-mediated disease currently relies heavily on CysLT1 receptor antagonists like montelukast or 5-lipoxygenase inhibitors like zileuton, direct inhibition of LTC4S represents a targeted therapeutic strategy to abolish CysLT production without affecting other eicosanoid pathways (PubMed: 9167032). Experimental inhibitors and compounds targeting the LTC4S/FLAP complex are currently being investigated for their potential to provide superior efficacy in chronic inflammatory and cardiovascular conditions (PubChem: CID 11954168).

Other names

LTC4 synthaseGlutathione S-transferase LTC4Leukotriene-C4 synthase

Inhibition of the enzymatic conjugation of leukotriene A4 with glutathione to produce leukotriene C4.