Information on EC 1.14.15.16 - vitamin D3 24-hydroxylase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.15.16
-
RECOMMENDED NAME
GeneOntology No.
vitamin D3 24-hydroxylase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = secalciferol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
(2)
-
-
-
calcitriol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitetrol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
(1)
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-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydroxylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Steroid biosynthesis
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)
This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. The enzyme can perform up to 6 rounds of hydroxylation of the substrate calcitriol leading to calcitroic acid. The human enzyme also shows 23-hydroxylating activity leading to 1,25 dihydroxyvitamin D3-26,23-lactone as end product while the mouse and rat enzymes do not. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
evaluation of the 3,5-dimethoxy and 3,4,5-trimethoxy derivatives of imidazole styrylbenzamide in chronic lymphocytic leukemia cells reveals that co-treatment of 1alpha,25-dihydroxyvitamin D3 plus inhibitor coordinately upregulates GADD45alpha and CDKN1A
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1alpha,23,25-trihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,25-dihydroxyvitamin D3-26,23-lactone + NADP+ + H2O
show the reaction diagram
1alpha,24(R)-dihydroxyvitamin D3 + NADPH + H+ + O2
?
show the reaction diagram
1alpha,24R,25-trihydroxyvitamin D3 + NADPH + O2
calcitroic acid + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxy-3-epi-vitamin D3 + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
1alpha,25-dihydroxy-3-epivitamin-D3 + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,23,25-trihydroxyvitamin D3 + 25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
after hydrogen abstraction of the C-23 position of 1alpha,25-dihydroxyvitamin D3, part of the substrate-radical intermediate is converted into 25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3, while a major part of them is converted into 1alpha,23,25-trihydroxyvitamin D3
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,23,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,23S,25,26-tetrahydroxyvitamin D3 + 1alpha,23S,25-trihydroxyvitamin D3 + 25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,24(R)-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,24,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,24R,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,25-dihydroxyvitamin D3-26,23-lactone + NADP+ + H2O
show the reaction diagram
-
C23-hydroxylation
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
24-oxo-1,23,25-trihydroxyvitamin D3 + 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3 + 1alpha,24R,25-trihydroxyvitamin D3 + 24-oxo-1,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
calcitroic acid + NADP+ + H2O
show the reaction diagram
1alpha-hydroxyvitamin D2 + NADPH + H+ + O2
1alpha,24-dihydroxyvitamin D2 + 1alpha,25-dihydroxyvitamin D2 + 26-carboxy-1alpha,24-dihydroxyvitamin D2 + NADP+ + H2O
show the reaction diagram
1beta,25-dihydroxy-3-epi-vitamin D3 + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
1beta,25-dihydroxy-3-epivitamin-D3 + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
1beta,25-dihydroxyvitamin D3 + NADPH + H+ + O2
? + NADP+ + H2O
show the reaction diagram
2-methylene-19-nor-(20R)-1,25-dihydroxyvitamin D3 + NADPH + H+ + O2
? + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 + NADPH + H+ + O2
? + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
23-oxo-24,25,26,27-tetranor-1alpha-hydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
calcitroic acid + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24,25,26,27-tetranor-1alpha,23-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
23-oxo-24,25,26,27-tetranor-1alpha-hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24-oxo-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
24,25,26,27-tetranor-1alpha,23-dihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24-oxo-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
24-oxo-1alpha,23,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
25-hydroxyvitamin D3 + NADPH + H+ + O2
1alpha,25-dihydroxyvitamin D3-26,23-lactone + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 + NADPH + H+ + O2
24,25,26,27-tetranor-23-hydroxyvitamin-D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24,25-dihydroxyvitamin D3 + NADP+ + H2O + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24-oxo-25-hydroxyvitamin D3 + 23(S),25-dihydroxyvitamin D3 + 24(R),25-dihydroxyvitamin D3 + 24-oxo-23(S),25-dihydoxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24R,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 + NADPH + H+ + O2
25,26,27-trinor-23-ene-vitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
the metabolite 25,26,27-trinor-23-ene-vitamin D3 is closely related with the C-23 hydroxylation pathway
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
secalciferol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxy-24-oxo-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23-dihydroxy-24,25,26,27-tetranor-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23,26-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,25-dihydroxy-23-oxo-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi-1alpha,23,26?trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi?1alpha,25?dihydroxy?23?oxo?vitamin D3.+ 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23-dihydroxy-24,25,26,27-tetranor-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epicalcitroic acid + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,24,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,25-dihydroxy-24-oxo-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxy-24-oxo-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23,25-trihydroxy-24-oxo-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,24,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-25,26,27-trinor-23,24-epoxide-1alpha-hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi?25,26,27?trinor?23,24?epoxide?1alpha?hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
calcidiol + 2 reduced adrenodoxin + 2 H+ + O2
secalciferol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
calcidiol + NADPH + H+ + O2
secalciferol + NADP+ + H2O
show the reaction diagram
calcitetrol + 2 reduced adrenodoxin + 2 H+ + O2
24-oxo-1alpha,25-dihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
calcitriol + 2 reduced adrenodoxin + 2 H+ + O2
calcitetrol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
calcitriol + NADPH + H+ + O2
calcitetrol + NADP+ + H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,24,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
1alpha,24R,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
1alpha,25-dihydroxyvitamin D3 + NADPH + H+ + O2
calcitroic acid + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
23-oxo-24,25,26,27-tetranor-1alpha-hydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
calcitroic acid + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24,25,26,27-tetranor-1alpha,23-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
23-oxo-24,25,26,27-tetranor-1alpha-hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24-oxo-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
24,25,26,27-tetranor-1alpha,23-dihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
24-oxo-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
24-oxo-1alpha,23,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
25-hydroxyvitamin D3 + NADPH + H+ + O2
1alpha,25-dihydroxyvitamin D3-26,23-lactone + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + H+ + O2
24,25-dihydroxyvitamin D3 + NADP+ + H2O + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxy-24-oxo-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23-dihydroxy-24,25,26,27-tetranor-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi-1alpha,23,26?trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi?1alpha,25?dihydroxy?23?oxo?vitamin D3.+ 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,23-dihydroxy-24,25,26,27-tetranor-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epicalcitroic acid + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,24,25-trihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,25-dihydroxy-24-oxo-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxy-24-oxo-vitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23,25-trihydroxy-24-oxo-vitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,23,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-1alpha,24,25-trihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-1alpha,25-dihydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3-epi-25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
3-epi-25,26,27-trinor-23-ene-1alpha-hydroxyvitamin D3 + 2 reduced adrenodoxin + 2 H+ + O2
3?epi?25,26,27?trinor?23,24?epoxide?1alpha?hydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
calcidiol + 2 reduced adrenodoxin + 2 H+ + O2
secalciferol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
calcidiol + NADPH + H+ + O2
secalciferol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
calcitetrol + 2 reduced adrenodoxin + 2 H+ + O2
24-oxo-1alpha,25-dihydroxyvitamin D3 + 2 oxidized adrenodoxin + H2O
show the reaction diagram
calcitriol + 2 reduced adrenodoxin + 2 H+ + O2
calcitetrol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adrenodoxin
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NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
24-hydroxylase activity is 20fold greater in Hyp mice relative to normal treated with calcium. In Hyp mice, treatment with calcium plus 1alpha,25-dihydroxyvitamin D3 results in a greater increase in 24-hydroxylase than treatment with either agent alone
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R,3S,5Z,7E,14x)-17-[(2R)-1-(1H-imidazol-1-yl)propan-2-yl]-2-methylidene-9,10-secoestra-5,7-diene-1,3-diol
-
potent and selective CYP24A1 inhibitor
(1R,3S,5Z,7E,14x)-17-[(2S)-7-cyclopropylheptan-2-yl]-2-methylidene-9,10-secoestra-5,7-diene-1,3-diol
-
potent and selective CYP24A1 inhibitor
(2R)-2-[(4E,7aR)-4-[(2Z)-2-[(5R)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propyl bromoacetate
-
-
(3R,5Z,7E,14x,17x,20S)-3-hydroxy-9,10-secochola-5,7,10-trien-24-yl 4-methylbenzenesulfonate
-
-
(E)-3-(4-styryl-1H-indol-1-yl)propyl benzenesulfinate
-
-
1-[3-(1H-imidazol-1-yl)propyl]-4-(3,5-dimethoxystyryl)-1H-indole
-
-
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1-[3-(1H-imidazol-1-yl)propyl]-4-styryl-1H-indole
-
-
1-[3-(1H-imidazol-1-yl)propyl]-5-styryl-1H-indole
-
-
1-[4-(1H-imidazol-1-yl)butyl]-4-(3,5-dimethoxystyryl)-1H-indole
-
-
-
1-[4-(1H-imidazol-1-yl)butyl]-4-styryl-1H-indole
-
-
1-[4-(1H-imidazol-1-yl)butyl]-5-styryl-1H-indole
-
-
2-(4-hydroxybenzyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one
-
-
-
24-carboxyl-25-hydroxyvitamin D3
-
-
24-difluoro-1,25-dihydroxyvitamin D3
-
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4-methyl-N-[3-(4-styryl-indol-1-yl)propyl]benzenesulfonamide
-
-
4-methyl-N-[4-(4-styryl-indol-1-yl)butyl]benzenesulfonamide
-
-
5-cyclohexylpentyl beta-D-maltoside
-
-
-
6-cyclohexylpentyl beta-D-maltoside
-
-
-
7-cyclohexylpentyl beta-D-maltoside
-
-
-
CHAPS
-
inhibits ligand binding to the CYP24A1:adrenodoxin complex at concentrations well below their reported critical micelle concentration (CMC) values
CTA018
-
-
CTA091
-
-
Facade-EM
-
-
-
Fos-choline-14
-
-
-
ketoconazole
liarozole
Metyrapone
-
complete inhibition at 5 mM
N-(3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-propyl)-4-methyl-benzenesulfonamide
-
-
-
N-(4-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-butyl)-4-methyl-benzenesulfonamide
-
-
-
n-dodecyl beta-D-maltoside
-
-
N-[2-(1H-imidazol-1-yl)-2-phenylethyl]-4-[(E)-2-phenylethenyl]benzamide
-
-
-
nonyl-beta-D-glucoside
-
-
octa ethylene glycol monodecyl ether
-
-
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SKF 525 A
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75% inhibition at 0.3 mM
toluene-4-sulfonic acid 3-(4-styryl-indol-1-yl)-propyl ester
-
-
toluene-4-sulfonic acid 3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1-yl)-propyl ester
-
-
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VID400
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i.e. (R)-N-(2-(1H-imidazol-1-yl)-2-phenylethyl)-4-chlorobiphenyl-4-carboxamide, exhibits strong and selective CYP24A1 inhibitory activity
vitamin D sulfonate
-
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1alpha,25-dihydroxyvitamin D3
-
renal 24-hydroxylase is significantly stimulated by 1alpha,25-dihydroxyvitamin D3 treatment in both normal and Hyp mice. In normal mice, 1alpha,25-dihydroxyvitamin D3 treatment is more effective than calcium in turning on 24-hydroxylase activity. In Hyp mice, treatment with calcium plus 1alpha,25-dihydroxyvitamin D3 results in a greater increase in 24-hydroxylase than treatment with either agent alone. 24-hydroxylase is 3fold, and 8fold greater in Hyp mice relative to normal treated with 1alpha,25-dihydroxyvitamin D3, and calcium plus 1alpha,25-dihydroxyvitamin D3, respectively
adrenodoxin
-
required for activity of the recombinant enzyme
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adrenodoxin reductase
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required for activity of the recombinant enzyme
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calcitriol
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calcitriol increases its own degradation in renal failure by increasing the enzymatic activity of 24-hydroxylase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00015
1alpha,25-dihydroxy-3-epi-vitamin D3
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in 0.1 mM Tris-HCl (pH 7.4), temperature not specified in the publication
0.00006 - 0.00114
1alpha,25-dihydroxyvitamin D3
0.0012
1beta,25-dihydroxy-3-epi-vitamin D3
-
in 0.1 mM Tris-HCl (pH 7.4), temperature not specified in the publication
0.00006
1beta,25-dihydroxyvitamin D3
-
in 0.1 mM Tris-HCl (pH 7.4), temperature not specified in the publication
0.00034
2-methylene-19-nor-(20R)-1,25-dihydroxyvitamin D3
-
in 20 mM Tris (pH 7.5), at 37C
0.00014
2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3
-
in 20 mM Tris (pH 7.5), at 37C
0.00018 - 0.00033
25-hydroxyvitamin D3
0.0086 - 0.009
calcitriol
additional information
additional information
-
substrate kinetics, overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0008 - 0.012
1alpha,25-dihydroxyvitamin D3
0.0017
2-methylene-19-nor-(20R)-1,25-dihydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
0.00025
2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
0.002
25-hydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.7 - 23.3
1alpha,25-dihydroxyvitamin D3
1953
4.9
2-methylene-19-nor-(20R)-1,25-dihydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
41640
1.8
2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
41639
6.1
25-hydroxyvitamin D3
Homo sapiens
-
in 20 mM Tris (pH 7.5), at 37C
4387
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00054
(E)-3-(4-styryl-1H-indol-1-yl)propyl benzenesulfinate
-
pH 7.5, 37C
0.000031
1-[3-(1H-imidazol-1-yl)propyl]-4-(3,5-dimethoxystyryl)-1H-indole
-
pH 7.5, 37C
-
0.000026
1-[3-(1H-imidazol-1-yl)propyl]-4-styryl-1H-indole
-
pH 7.5, 37C
0.000037
1-[3-(1H-imidazol-1-yl)propyl]-5-styryl-1H-indole
-
pH 7.5, 37C
0.000014
1-[4-(1H-imidazol-1-yl)butyl]-4-(3,5-dimethoxystyryl)-1H-indole
-
0.000037
1-[4-(1H-imidazol-1-yl)butyl]-5-styryl-1H-indole
-
pH 7.5, 37C
0.00034
4-methyl-N-[3-(4-styryl-indol-1-yl)propyl]benzenesulfonamide
-
pH 7.5, 37C
0.00023
4-methyl-N-[4-(4-styryl-indol-1-yl)butyl]benzenesulfonamide
-
pH 7.5, 37C
1.05
5-cyclohexylpentyl beta-D-maltoside
-
pH and temperature not specified in the publication
-
1.88
6-cyclohexylpentyl beta-D-maltoside
-
pH and temperature not specified in the publication
-
0.95
7-cyclohexylpentyl beta-D-maltoside
-
pH and temperature not specified in the publication
-
3.65
CHAPS
-
pH and temperature not specified in the publication
0.37
Facade-EM
-
pH and temperature not specified in the publication
-
1.67
Fos-choline-14
-
pH and temperature not specified in the publication
-
0.000035
ketoconazole
-
pH 7.5, 37C
0.00073
N-(3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-propyl)-4-methyl-benzenesulfonamide
-
pH 7.5, 37C
-
0.00074
N-(4-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-butyl)-4-methyl-benzenesulfonamide
-
pH 7.5, 37C
-
0.29 - 6.9
n-dodecyl beta-D-maltoside
0.00064
toluene-4-sulfonic acid 3-(4-styryl-indol-1-yl)-propyl ester
-
pH 7.5, 37C
0.00119
toluene-4-sulfonic acid 3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1-yl)-propyl ester
-
pH 7.5, 37C
-
0.000039
vitamin D sulfonate
-
pH 7.5, 37C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0076
(E)-3-(4-styryl-1H-indol-1-yl)propyl benzenesulfinate
Homo sapiens
-
pH 7.5, 37C
0.00044
1-[3-(1H-imidazol-1-yl)propyl]-4-(3,5-dimethoxystyryl)-1H-indole
Homo sapiens
-
pH 7.5, 37C
-
0.00036
1-[3-(1H-imidazol-1-yl)propyl]-4-styryl-1H-indole
Homo sapiens
-
pH 7.5, 37C
0.00052
1-[3-(1H-imidazol-1-yl)propyl]-5-styryl-1H-indole
Homo sapiens
-
pH 7.5, 37C
0.00019
1-[4-(1H-imidazol-1-yl)butyl]-4-(3,5-dimethoxystyryl)-1H-indole
Homo sapiens
-
pH 7.5, 37C
-
0.0002
1-[4-(1H-imidazol-1-yl)butyl]-4-styryl-1H-indole
Homo sapiens
-
pH 7.5, 37C
0.00052
1-[4-(1H-imidazol-1-yl)butyl]-5-styryl-1H-indole
Homo sapiens
-
pH 7.5, 37C
0.0048
4-methyl-N-[3-(4-styryl-indol-1-yl)propyl]benzenesulfonamide
Homo sapiens
-
pH 7.5, 37C
0.0033
4-methyl-N-[4-(4-styryl-indol-1-yl)butyl]benzenesulfonamide
Homo sapiens
-
pH 7.5, 37C
0.00047
ketoconazole
Homo sapiens
-
pH 7.5, 37C
0.0104
N-(3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-propyl)-4-methyl-benzenesulfonamide
Homo sapiens
-
pH 7.5, 37C
-
0.0105
N-(4-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1yl)-butyl)-4-methyl-benzenesulfonamide
Homo sapiens
-
pH 7.5, 37C
-
0.0003
N-[2-(1H-imidazol-1-yl)-2-phenylethyl]-4-[(E)-2-phenylethenyl]benzamide
Homo sapiens
-
pH 7.5, 37C
-
0.009
toluene-4-sulfonic acid 3-(4-styryl-indol-1-yl)-propyl ester
Homo sapiens
-
pH 7.5, 37C
0.0169
toluene-4-sulfonic acid 3-(4-[2-(3,5-dimethoxy-phenyl)-vinyl]-indol-1-yl)-propyl ester
Homo sapiens
-
pH 7.5, 37C
-
0.000015
VID400
Homo sapiens
-
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
the enzyme is detected in the yolk sac as early as day 12 in the embryonic period and until the end of gestation
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55450
-
mature enzyme, calculated from amino acid sequence
59500
-
calculated from amino acid sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant active His-tagged enzyme from Escherichia coli membranes by nickel affinity and hydrophobic interaction chromatography and dialysis, adrenodoxin-affinity chromatography is not successful
-
recombinant N-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli strain DH5alpha F'IQ by nickel affinity chromatography and gel filtration, copurification with added recombinant bovine adrenodoxin for enzyme-cofctor complex preparation
-
recombinant N-terminally maltose-binding-protein fused enzyme from Escherichia coli by affinity chromatography to homogeneity
-
Talon metal affinity column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in chinese hamster lung fibroblast cells (V79-4 cells)
-
expressed in Escherichia coli
expressed in Escherichia coli BL21-Gold(DE3) and Rosetta 2(DE3) cells
-
expressed in Escherichia coli JM109 cells
expressed in Sf21 insect cells using the previously cloned cDNA in baculovirus (AcNPV-P450cc24), solubilized mitochondrial protein from Sf21 cells infected with recombinant virus AcNPV-P450cc24 cDNA express 24-hydroxylase activity when reconstituted with bovine adrenodoxin, adrenodoxin reductase, and NADPH
-
expressed in V79-CYP24 or OK (CCL-1840) cells
-
gene CYP24A1, cloned from leukocyte DNA, DNA and amino acid sequence determination and analysis, expression analysis by RT-PCR, recombinant expression of wild-type and mutant CYP24A1 cDNAs in JEG-3 cells. The mammalian two-hybrid assay system consisting of the retinoid-X receptor and vitamin D receptor in JEG-3 cells is used as a simple, sensitive, quantitative assay of enzyme activity
-
gene CYP24A1, functional recombinant His-tagged enzyme expression in Escherichia coli membranes
-
gene CYP24A1, overexpression of N-terminally maltose-binding-protein fused enzyme in Escherichia coli
-
gene CYP24A1, recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain DH5alpha F'IQ
-
mutant enzymes are expressed in Escherichia coli BL21(DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CYP24A1 is transcriptionally induced in vitamin D target cells by the action of 1alpha,25-dihydroxyvitamin D3
enzyme expression is upregulated in cancer cells
-
intraperitoneal injection of 1,25-dihydroxyvitamin D3 induces dose- and time-dependent increases in both 24-OHase mRNA abundance and enzyme activity in mouse kidney reaching a maximum between 4-8 h, after which it decreases and then maintains a steady value between 18-72 h. Similarly, 1,25-dihydroxyvitamin D3-induced increases in both 24-OHase mRNA and activity are apparent in the duodenum. Although 1,25-dihydroxyvitamin D3 markedly the amount of 24-OHase mRNA in skin between 4 and 6 h, enzyme activity is not detected in this tissue. Pretreatment of mice with cycloheximide (0.4mg/g) potentiates the increase in 24-OHase mRNA abundance but blocks the increase in 24-OHase activity, induced by 1,25-dihydroxyvitamin D3 in kidney and duodenum
-
methyltransferase inhibitor 5-aza-2'-deoxycytidine treatment results in an over 50fold induction of CYP24A1 mRNA expression in Coga1A and HT-29 cells. In colon cancer cells, CYP24A1 gene expression is inducible by methyltransferase and some histone deacetylase inhibitors in a cell line-dependent manner
-
replacement of calcitriol (3 ng per day) significantly increases 24-hydroxylase activity by 17% in rats with renal failure, although the activity remains 15% lower than the controls
-
the enzymatic activity of intestinal 24-hydroxylase is significantly lower in renal failure rats compared to control sham operated rats
-
the enzyme is upregulated in tumor cells compared with normal tissue
-
the vitamin D receptor bound to 1alpha,25(OH)2D3 induces expression of mitochondrial cytochrome P450 24A1
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E143del
-
naturally occuring mutation
E147del
-
naturally occuring mutation
E149del
-
naturally occuring mutation
E151X
-
naturally occuring mutation
E322K
-
naturally occuring mutation
L409S
-
naturally occuring missense mutation, found on only one allele, no other mutation is found in exons or in at least 30 bp of each intron/exon junction. ThecL409S mutant has about 32% of wild-type 24-hydroxylase activity
R159Q
-
naturally occuring mutation
R396W
-
naturally occuring mutation
V391L
-
the mutation converts the enzyme from a catabolic 1alpha,25-dihydroxyvitamin-D3-24-hydroxylase into an anabolic 1alpha-hydroxyvitamin-D3-25-hydroxylase. The mutant enzyme retains its basal ability to catabolize 1alpha,25-dihydroxyvitamin D3 via C24 hydroxylation
V391L/A326G
-
the mutant enzyme continues to form 1alpha,25-dihydroxyvitamin D3 from 1alpha-hydroxyvitamin-D3, but this initial product is diverted via the C23 hydroxylation pathway into 1alpha,25-dihydroxyvitamin-D3-26,23-lactone
W210R
-
naturally occuring mutation
W268X
-
naturally occuring mutation
I500F
-
the mutant shows quite a different metabolism of 1alpha,25-dihydroxyvitamin D3 from both human and rat CYP24A1
I500L
-
the mutant also shows the C-23 oxidation pathway
I500T
-
the mutant also shows the C-23 oxidation pathway
I500V
-
the mutant also shows the C-23 oxidation pathway
S57D
-
site-directed mutagenesis
T416A
-
the metabolic pattern by the mutant remains rat CYP24A1wild type
T416F
-
the mutant has reaction specificity similar to human CYP24A1 by also showing the C-23 oxidation pathway
T416I
-
the mutant has reaction specificity similar to human CYP24A1 by also showing the C-23 oxidation pathway
T416M
-
the mutant also shows the C-23 oxidation pathway
T416S
-
the metabolic pattern by the mutant remains rat CYP24A1wild type
T416V
-
the mutant has reaction specificity similar to human CYP24A1 by also showing the C-23 oxidation pathway
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
elevated tumor CYP24A1 expression is associated with a poor prognosis