LTA4H
LTA4H (leukotriene A4 hydrolase) is a bifunctional zinc metalloenzyme with both epoxide hydrolase and aminopeptidase activities. It catalyses the final step in the biosynthesis of the pro-inflammatory mediator leukotriene B4, and it also inactivates the neutrophil attractant Pro-Gly-Pro. Browse Assay Genie's current range of LTA4H research reagents below, or read on for the biology behind the target.
LTA4H is a zinc metalloenzyme that combines two distinct catalytic activities in one protein. As an epoxide hydrolase, it converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a pro-inflammatory mediator. This is the final step in LTB4 biosynthesis. LTA4H can also use LTA5 as a substrate, although less effectively than LTA4, and produces LTB5. Its second activity is aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides.
The two activities place LTA4H on both sides of the inflammatory response. Its aminopeptidase activity cleaves and inactivates the tripeptide Pro-Gly-Pro (PGP), another neutrophil attractant. PGP is a bioactive fragment of collagen generated by matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL). NCBI Gene notes that PGP is a neutrophil chemoattractant and a biomarker for chronic obstructive pulmonary disease (COPD). LTA4H is also involved in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid. These lipid mediators have potent anti-inflammatory and pro-resolving actions.
The LTA4H gene encodes a cytoplasmic protein that belongs to the peptidase M1 family and is classed by HGNC in the M1 metallopeptidases group. Several transcript variants encoding different isoforms have been reported. Orthologues are annotated in mouse and rat as Lta4h, which supports comparative work on leukotriene biology. Researchers studying LTA4H protein function, whether as a source of LTB4 or as a PGP-degrading enzyme, can use it as a model of a single enzyme with opposing effects on inflammation.
LTA4H carries out the final step in LTB4 production, converting LTA4 to this pro-inflammatory mediator.
Its aminopeptidase activity inactivates Pro-Gly-Pro, a collagen-derived neutrophil attractant generated through MMP9 and PREPL.
PGP, which LTA4H degrades, is described as a neutrophil chemoattractant and a biomarker for chronic obstructive pulmonary disease.
LTA4H contributes to biosynthesis of resolvin E1 and 18S-resolvin E1, lipid mediators with anti-inflammatory and pro-resolving actions.
LTA4H is a bifunctional zinc metalloenzyme. Its epoxide hydrolase activity converts LTA4 to the pro-inflammatory mediator LTB4. Its aminopeptidase activity cleaves substrates such as the neutrophil attractant Pro-Gly-Pro, so it can both promote and counteract inflammation.
The HGNC name is leukotriene A4 hydrolase, and UniProt lists it as Leukotriene A-4 hydrolase. No alternative symbols are recorded. NCBI Gene reports several transcript variants that encode different isoforms, so check which isoform a reagent recognises before use.
Mouse and rat each have an orthologue named Lta4h. NCBI Gene links the enzyme's PGP-degrading activity to COPD, as PGP is a biomarker for the disease. Check the datasheet of any product for its validated reactivity.
Related targets and pathway partners with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P09960; product specifications from Assay Genie datasheets.