KEGG   ENZYME: 3.1.3.76Help
Entry
EC 3.1.3.76                 Enzyme                                 

Name
lipid-phosphate phosphatase;
hydroxy fatty acid phosphatase;
dihydroxy fatty acid phosphatase;
hydroxy lipid phosphatase;
sEH (ambiguous);
soluble epoxide hydrolase (ambiguous)
Class
Hydrolases;
Acting on ester bonds;
Phosphoric-monoester hydrolases
BRITE hierarchy
Sysname
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate phosphohydrolase
Reaction(IUBMB)
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate [RN:R07582]
Reaction(KEGG)
Substrate
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate [CPD:C15989];
H2O [CPD:C00001]
Product
(9S,10S)-9,10-dihydroxyoctadecanoate [CPD:C15988];
phosphate [CPD:C00009]
Comment
Requires Mg2+ for maximal activity. The enzyme from mammals is a bifunctional enzyme: the N-terminal domain exhibits lipid-phosphate-phosphatase activity and the C-terminal domain has the activity of EC 3.3.2.10, soluble epoxide hydrolase (sEH) [1]. The best substrates for this enzyme are 10-hydroxy-9-(phosphonooxy)octadecanoates, with the threo- form being a better substrate than the erythro- form [1]. The phosphatase activity is not found in plant sEH or in EC 3.3.2.9, microsomal epoxide hydrolase, from mammals [1].
History
EC 3.1.3.76 created 2006
Reference
1  [PMID:12574510]
  Authors
Newman JW, Morisseau C, Harris TR, Hammock BD.
  Title
The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1558-63.
  Sequence
[hsa:2053]
Reference
2  [PMID:12574508]
  Authors
Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M.
  Title
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1552-7.
Reference
3  [PMID:15822179]
  Authors
Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Journal
Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-33.
Reference
4  [PMID:16142916]
  Authors
Tran KL, Aronov PA, Tanaka H, Newman JW, Hammock BD, Morisseau C.
  Title
Lipid sulfates and sulfonates are allosteric competitive inhibitors of the N-terminal phosphatase activity of the mammalian soluble epoxide hydrolase.
  Journal
Biochemistry. 44 (2005) 12179-87.
Reference
5  [PMID:15748653]
  Authors
Newman JW, Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: their roles and interactions with lipid metabolism.
  Journal
Prog. Lipid. Res. 44 (2005) 1-51.
Reference
6  [PMID:15196990]
  Authors
Srivastava PK, Sharma VK, Kalonia DS, Grant DF.
  Title
Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure.
  Journal
Arch. Biochem. Biophys. 427 (2004) 164-9.
Reference
7  [PMID:15096040]
  Authors
Gomez GA, Morisseau C, Hammock BD, Christianson DW.
  Title
Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis.
  Journal
Biochemistry. 43 (2004) 4716-23.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

KEGG   ENZYME: 3.3.2.10Help
Entry
EC 3.3.2.10                 Enzyme                                 

Name
soluble epoxide hydrolase;
epoxide hydrase (ambiguous);
epoxide hydratase (ambiguous);
arene-oxide hydratase (ambiguous);
aryl epoxide hydrase (ambiguous);
trans-stilbene oxide hydrolase;
sEH;
cytosolic epoxide hydrolase
Class
Hydrolases;
Acting on ether bonds;
Ether hydrolases
BRITE hierarchy
Sysname
epoxide hydrolase
Reaction(IUBMB)
an epoxide + H2O = a glycol [RN:R02822]
Reaction(KEGG)
Substrate
epoxide [CPD:C00722];
H2O [CPD:C00001]
Product
glycol [CPD:C15588]
Comment
Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl---enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. 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) [7].
History
EC 3.3.2.10 created 2006 (EC 3.3.2.3 part-incorporated 2006)
Pathway
Arachidonic acid metabolism
Chloroalkane and chloroalkene degradation
Metabolic pathways
Microbial metabolism in diverse environments
Orthology
K08726  
soluble epoxide hydrolase
Genes
HSA: 
2053(EPHX2)
PTR: 
464074(EPHX2)
PPS: 
100990932(EPHX2)
GGO: 
101136750(EPHX2)
PON: 
100172736(EPHX2)
MCC: 
712926(EPHX2)
MCF: 
102134633(EPHX2)
MMU: 
13850(Ephx2)
RNO: 
65030(Ephx2)
CGE: 
100757328(Ephx2)
HGL: 
101715352(Ephx2)
TUP: 
102480725(EPHX2)
CFA: 
477373(EPHX2)
AML: 
100483572(EPHX2)
FCA: 
101092355(EPHX2)
PTG: 
102957184(EPHX2)
BTA: 
511716(EPHX2) 785508
BOM: 
102267808(EPHX2)
PHD: 
102326909(EPHX2)
CHX: 
102185835(EPHX2)
OAS: 
101106654(EPHX2)
SSC: 
414425(EPHX2)
CFR: 
102517269(EPHX2)
BACU: 
103015729(EPHX2)
LVE: 
103082628(EPHX2)
ECB: 
100060414(EPHX2)
MYB: 
102255588(EPHX2)
MYD: 
102755564(EPHX2)
PALE: 
102886924(EPHX2)
MDO: 
100030580(EPHX2)
SHR: 
OAA: 
100093187(EPHX2)
GGA: 
421999(EPHX2)
MGP: 
FAB: 
101820851(EPHX2)
PHI: 
FPG: 
101922601(EPHX2)
FCH: 
102047869(EPHX2)
CLV: 
102084991(EPHX2)
ASN: 
102382847(EPHX2)
AMJ: 
PSS: 
102463793(EPHX2)
CMY: 
102944771(EPHX2)
ACS: 
100564154(ephx2)
PBI: 
XLA: 
447032(ephx2)
XTR: 
448759(ephx2)
DRE: 
494099(ephx2)
TRU: 
MZE: 
OLA: 
XMA: 
BFO: 
CIN: 
SPU: 
590376 590472(EH1) 752510(eh2)
NVE: 
TAD: 
CIC: 
YLI: 
NCR: 
MGR: 
PNO: 
PTE: 
PFJ: 
DSQ: 
SHS: 
PCO: 
PSQ: 
ADL: 
FME: 
LBC: 
MRR: 
CCI: 
SCM: 
ABP: 
AGABI1DRAFT38499(AGABI1DRAFT_38499) AGABI1DRAFT70817(AGABI1DRAFT_70817)
ABV: 
AGABI2DRAFT78715(AGABI2DRAFT_78715)
CPUT: 
SLA: 
UMA: 
PFP: 
PGR: 
MLR: 
WSE: 
ACAN: 
PIF: 
 » show all
Taxonomy
Reference
1  [PMID:12574510]
  Authors
Newman JW, Morisseau C, Harris TR, Hammock BD.
  Title
The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1558-63.
  Sequence
[hsa:2053]
Reference
2  [PMID:12574508]
  Authors
Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M.
  Title
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1552-7.
  Sequence
[hsa:2053] [rno:65030]
Reference
3  [PMID:4584115]
  Authors
Oesch F.
  Title
Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.
  Journal
Xenobiotica. 3 (1973) 305-40.
Reference
4  [PMID:15822179]
  Authors
Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Journal
Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-33.
Reference
5  [PMID:11090543]
  Authors
Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL.
  Title
Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.
  Journal
Circ. Res. 87 (2000) 992-8.
Reference
6
  Authors
Lacourciere, G.M. and Armstrong, R.N.
  Title
The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate.
  Journal
J. Am. Chem. Soc. 115 (1993) 10466-10456.
Reference
7  [PMID:11154734]
  Authors
Fretland AJ, Omiecinski CJ.
  Title
Epoxide hydrolases: biochemistry and molecular biology.
  Journal
Chem. Biol. Interact. 129 (2000) 41-59.
Reference
8  [PMID:7840649]
  Authors
Zeldin DC, Wei S, Falck JR, Hammock BD, Snapper JR, Capdevila JH.
  Title
Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis.
  Journal
Arch. Biochem. Biophys. 316 (1995) 443-51.
Reference
9  [PMID:3009453]
  Authors
Haeggstrom J, Meijer J, Radmark O.
  Title
Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.
  Journal
J. Biol. Chem. 261 (1986) 6332-7.
Reference
10 [PMID:15748653]
  Authors
Newman JW, Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: their roles and interactions with lipid metabolism.
  Journal
Prog. Lipid. Res. 44 (2005) 1-51.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
UM-BBD (Biocatalysis/Biodegradation Database): 
BRENDA, the Enzyme Database: 
CAS: 
9048-63-9

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