ExplorEnz: EC 3.3.2.6

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3.3.2.6

Accepted name:

leukotriene-A₄ hydrolase

Reaction:

leukotriene A₄ + H₂O = leukotriene B₄

Glossary:

leukotriene A₄ = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
leukotriene B₄ = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Other name(s):

LTA₄ hydrolase; LTA4H; leukotriene A₄ hydrolase

Systematic name:

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase

Comments:

This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A₄ into leukotriene B₄, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A₄ into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A₄ hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [5].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 90119-07-6

References:

1.	Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of leukotriene A₄ hydrolase from rat neutrophils. Biochim. Biophys. Acta 840 (1985) 43–50. [DOI] [PMID: 3995081]
2.	Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A₄ hydrolase - complete primary structure of an enzyme involved in eicosanoid synthesis. J. Biol. Chem. 262 (1987) 13873–13876. [PMID: 3654641]
3.	Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A₄. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453]
4.	Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653]
5.	Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734]
6.	Orning, L., Gierse, J.K. and Fitzpatrick, F.A. The bifunctional enzyme leukotriene-A₄ hydrolase is an arginine aminopeptidase of high efficiency and specificity. J. Biol. Chem. 269 (1994) 11269. [PMID: 8157657]
7.	Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto, H., Takaku, F. and Shimizu, T. Leukotriene A₄ hydrolase in the human lung. Inactivation of the enzyme with leukotriene A₄ isomers. J. Biol. Chem. 262 (1987) 10200–10205. [PMID: 3038871]

[EC 3.3.2.6 created 1989, modified 2006]