leukotriene-A4 hydrolase;
LTA4 hydrolase;
LTA4H;
leukotriene A4 hydrolase

Hydrolases;
Acting on ether bonds;
Ether hydrolases

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

leukotriene A4 + H2O = leukotriene B4 [RN:R03057]

R03057

leukotriene A4 [CPD:C00909];
H2O [CPD:C00001]

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].

1  [PMID:3995081]

Evans JF, Dupuis P, Ford-Hutchinson AW.

Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils.

Biochim. Biophys. Acta. 840 (1985) 43-50.

Rattus norvegicus [GN:rno]

2  [PMID:3654641]

Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H, Shimizu T, Seyama Y, 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) 13873-6.

Homo sapiens [GN:hsa]

3  [PMID:3009453]

Haeggstrom J, Meijer J, Radmark 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) 6332-7.

Mus musculus [GN:mmu]

4  [PMID:15748653]

Newman JW, Morisseau C, Hammock BD.

Epoxide hydrolases: their roles and interactions with lipid metabolism.

Prog. Lipid. Res. 44 (2005) 1-51.

Homo sapiens [GN:hsa], Mus musculus [GN:mmu], Rattus norvegicus [GN:rno], Saccharomyces cerevisiae [GN:sce], Xenopus laevis

5  [PMID:11154734]

Fretland AJ, Omiecinski CJ.

Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact. 129 (2000) 41-59.

Homo sapiens [GN:hsa]

6  [PMID:8157657]

Orning L, Gierse JK, Fitzpatrick FA.

The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity.

J. Biol. Chem. 269 (1994) 11269-73.

Homo sapiens [GN:hsa], Mus musculus [GN:mmu]

7  [PMID:3038871]

Ohishi N, Izumi T, Minami M, Kitamura S, Seyama Y, Ohkawa S, Terao S, Yotsumoto H, Takaku F, Shimizu T.

Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.

J. Biol. Chem. 262 (1987) 10200-5.

Homo sapiens [GN:hsa]