LTA4n

LTA4n, more commonly referred to as leukotriene A4 hydrolase (LTA4H), is a cytosolic zinc-dependent metalloenzyme that occupies a central role in the inflammatory arm of arachidonic acid metabolism. It is encoded by the LTA4H gene in humans and is expressed in a range of cell types, including neutrophils and macrophages.

The enzyme has two distinct activities. The hydrolase activity converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemoattractant and activator of neutrophils. The aminopeptidase activity removes N-terminal amino acids from certain peptides, notably degrading the neutrophil chemoattractant peptide Pro-Gly-Pro (PGP) and related substrates. These two activities can be differentially regulated, allowing LTA4H to both promote and restrain inflammation depending on context.

The hydrolase activity links LTA4H to the 5-lipoxygenase pathway, generating LTB4 that signals through BLT receptors to recruit and activate leukocytes. The aminopeptidase function can limit neutrophil recruitment by degrading pro-inflammatory peptide signals, providing a counterbalance to LTB4 production. The enzyme’s dual functionality is sometimes described as bifunctional, with separate active sites or conformations supporting each activity.

Clinical and research relevance centers on inflammation and infectious disease. Variations in LTA4H activity or expression influence inflammatory responses in various settings, including airway disease and tuberculosis-related inflammation. Because of its dual roles, LTA4H is studied as a potential target for anti-inflammatory therapies, with interest in modulating either LTB4 production or PGP degradation to achieve desired immune outcomes.