Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.3.2.6

Official Name

leukotriene-A4 hydrolase

Name from literature

leukotriene a4 hydrolase

Pathway from literature

biosynthesis of leukotriene B4

Pathway from KEGG

Lipid Metabolism; Arachidonic acid metabolism; map00590

Organisms

Human (9606)

Genome localization

12q22[4048 ],

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 3.2.2.10, 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) [3].

Rate-limiting Description

"These results were explained after a comparison of the rates of synthesis of these 5-lipoxygenase metabolites in the presence and absence of added arachidonic acid which led to the conclusion that leukotriene A hydrolase, the enzyme catalysing the formation of LTB4, was saturated with substrate and rate-limiting for LTB4 synthesis during A23187 stimulation." (1311589)

"Since delta 6-trans-leukotriene B4 represents the nonenzymatic decomposition of leukotriene A4, we suggest that one of the rate-limiting steps in the synthesis of leukotriene B4 is the leukotriene A4 hydrolase." (6329309)

"Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator." (12865451)

Regulatory Information

Regulatory type

Detail

phosphorylation;

"LTA-H is widely spread in many mammalian tissues, although it appears to be inactive in many cases. Regulation of this enzyme's activity by phosphorylation of a serine at residue 415 has recently been described." (10320802#9395533)

key enzyme;

"Leukotriene A4 hydrolase is a key enzyme in the biosynthesis of leukotriene B4, a potent pro-inflammatory compound." (8982402)

phosphorylation;

P09960

Gene ontology

Gene ontology

GO:0008270 (F) zinc ion binding [P09960 ];
GO:0006954 (P) inflammatory response [P09960 ];
GO:0006508 (P) proteolysis [P09960 ];
GO:0008237 (F) metallopeptidase activity [P09960 ];
GO:0004463 (F) leukotriene-A4 hydrolase activity [P09960 ];
GO:0019370 (P) leukotriene biosynthetic process [P09960 ];
GO:0005737 (C) cytoplasm [P09960 ];
GO:0005515 (F) protein binding [P09960 ];
GO:0004301 (F) epoxide hydrolase activity [P09960 ];

Subcellular localization

Localization

cytoplasm [P09960 ];

Links

SwissProt

P09960

Entrez Gene

4048

HPRD

01056



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  Last Modified: 2009-03-24  
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