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Information on EC 1.14.14.78 - phylloquinone omega-hydroxylase and Organism(s) Homo sapiens

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IUBMB Comments
A cytochrome P-450 (heme-thiolate) protein. Isolated from human tissue. The enzyme will also act on menaquinone-4. Prolonged action of CYP4F2, but not CYP4F11, on the omega hydroxyl group oxidizes it to the corresponding carboxylic acid. CYP4F2 also oxidizes leukotriene B4; see EC 1.14.13.30, leukotriene-B4 20-monooxygenase .
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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
cytochrome p450 4f11, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CYP4F11
CYP4F2
cytochrome P450 4F11
-
-
leukotriene B4 omega-hydroxylase
-
-
vitamin K1 omega-hydroxylase
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
phylloquinone,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (omega-hydroxyphylloquinone forming)
A cytochrome P-450 (heme-thiolate) protein. Isolated from human tissue. The enzyme will also act on menaquinone-4. Prolonged action of CYP4F2, but not CYP4F11, on the omega hydroxyl group oxidizes it to the corresponding carboxylic acid. CYP4F2 also oxidizes leukotriene B4; see EC 1.14.13.30, leukotriene-B4 20-monooxygenase [1].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-hydroxypalmitate + [reduced NADPH-hemoprotein reductase] + O2
3,16-dihydroxypalmitate + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
3-hydroxystearate + [reduced NADPH-hemoprotein reductase] + O2
3,18-dihydroxystearate + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
arachidonic acid + [reduced NADPH-hemoprotein reductase] + O2
(5Z,8Z,11Z,14Z)-20-hydroxyeicosatetraenoic acid + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
arachidonic acid + [reduced NADPH-hemoprotein reductase] + O2
20-hydroxyarachidonic acid + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
arachidonic acid + [reduced NADPH-hemoprotein reductase] + O2
?
show the reaction diagram
-
-
-
-
?
leukotriene B4 + [reduced NADPH-hemoprotein reductase] + O2
20-hydroxyleukotriene B4 + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
menaquinone-4 + [reduced NADPH-hemoprotein reductase] + O2
omega-hydroxymenaquinone-4 + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
oleic acid + [reduced NADPH-hemoprotein reductase] + O2
18-hydroxyoleic acid + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
palmitic acid + [reduced NADPH-hemoprotein reductase] + O2
16-hydroxypalmitic acid + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
phylloquinone + [reduced NADPH-hemoprotein reductase] + O2
omega-hydroxyphylloquinone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme exhibits tocopherol-omega-hydroxylase activity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
menaquinone-4 + [reduced NADPH-hemoprotein reductase] + O2
omega-hydroxymenaquinone-4 + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
phylloquinone + [reduced NADPH-hemoprotein reductase] + O2
omega-hydroxyphylloquinone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme exhibits tocopherol-omega-hydroxylase activity
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
contains Fe2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
prostaglandin A1
-
-
additional information
-
unaffected by lauric acid, palmitic acid, and prostaglandin F2alpha
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0564 - 0.074
3-hydroxypalmitate
0.055
3-hydroxystearate
-
in 100 mM potassium phosphate buffer (pH 7.4), at 37°C
0.0235 - 0.08
arachidonic acid
0.085
oleic acid
-
at pH 7.4 and 37°C
0.047
palmitic acid
-
at pH 7.4 and 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.458
3-hydroxypalmitate
-
at pH 7.4 and 37°C
0.009
arachidonic acid
-
at pH 7.4 and 37°C
0.02
oleic acid
-
at pH 7.4 and 37°C
0.03
palmitic acid
-
at pH 7.4 and 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6.17
3-hydroxypalmitate
-
at pH 7.4 and 37°C
0.12
arachidonic acid
-
at pH 7.4 and 37°C
0.2
oleic acid
-
at pH 7.4 and 37°C
0.63
palmitic acid
-
at pH 7.4 and 37°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
CYP4F2 is the principle leukotriene B4 omega-hydroxylating enzyme expressed in human liver and plays an important role in regulating circulating as well as hepatic levels of this powerful proinflammatory eicosanoid
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CP4F2_HUMAN
520
1
59853
Swiss-Prot
Secretory Pathway (Reliability: 1)
CP4FB_HUMAN
524
1
60146
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
-
x * 50000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 50000, SDS-PAGE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+-NTA agarose column chromatography, Biogel HTP hydroxylapatite column chromatography, and aminopropyl SPE column chromatography
-
tryptamine CH-Sepharose column chromatography, DE-53 cellulose column chromatography, and Hypatite C column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
retinoic acid can regulate CYP4F2 gene activity with RXRalpha heterodimers stimulating while RARalpha functioning to repress CYP4F2 gene expression
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Parker, R.S.; Sontag, T.J.; Swanson, J.E.; McCormick, C.C.
Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism
Ann. N. Y. Acad. Sci.
1031
13-21
2004
Homo sapiens
Manually annotated by BRENDA team
Jin, R.; Koop, D.R.; Raucy, J.L.; Lasker, J.M.
Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent leukotriene B4
Arch. Biochem. Biophys.
359
89-98
1998
Homo sapiens
Manually annotated by BRENDA team
Tang, Z.; Salamanca-Pinzon, S.; Wu, Z.; Xiao, Y.; Guengerich, F.
Human cytochrome P450 4F11: Heterologous expression in bacteria, purification, and characterization of catalytic function
Arch. Biochem. Biophys.
494
86-93
2010
Homo sapiens
Manually annotated by BRENDA team
Zhang, X.; Hardwick, J.P.
Regulation of CYP4F2 leukotriene B4 omega-hydroxylase by retinoic acids in HepG2 cells
Biochem. Biophys. Res. Commun.
279
864-871
2000
Homo sapiens
Manually annotated by BRENDA team
Edson, K.Z.; Prasad, B.; Unadkat, J.D.; Suhara, Y.; Okano, T.; Guengerich, F.P.; Rettie, A.E.
Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11
Biochemistry
52
8276-8285
2013
Homo sapiens
Manually annotated by BRENDA team
Dhar, M.; Sepkovic, D.W.; Hirani, V.; Magnusson, R.P.; Lasker, J.M.
Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11
J. Lipid Res.
49
612-624
2008
Homo sapiens
Manually annotated by BRENDA team
Powell, P.K.; Wolf, I.; Jin, R.; Lasker, J.M.
Metabolism of arachidonic acid to 20-hydroxy-5,8,11,14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11
J. Pharmacol. Exp. Ther.
285
1327-1336
1998
Homo sapiens
Manually annotated by BRENDA team