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Enzyme Nomenclature
Information on EC 1.14.13.96 - 5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase
Word Map on EC 1.14.13.96
- 1.14.13.96
- bile
- cholesterol
-
cholic
-
7alpha-hydroxylase
- hepatocyte
-
chenodeoxycholic
- cyp7a1
-
nadph-cytochrome
-
4alpha
-
alpha1-fetoprotein
-
farnesoid
-
ferric
-
acid-mediated
-
hnf4alpha
-
3-nitrotyrosine-containing
-
o-deethylase
-
p-nitrophenetole
- metyrapone
-
cubic
- tetranitromethane
-
rhombic
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
1.14.13.96
-
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RECOMMENDED NAME
GeneOntology No.
5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5beta-cholestane-3alpha,7alpha-diol + NADPH + H+ + O2 = 5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+ + H2O
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SYSTEMATIC NAME
IUBMB Comments
5beta-cholestane-3alpha,7alpha-diol,NADPH:oxygen oxidoreductase (12alpha-hydroxylating)
A heme-thiolate protein (P-450). This is the key enzyme in the biosynthesis of the bile acid cholic acid (3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoic acid). The activity of this enzyme determines the biosynthetic ratio between cholic acid and chenodeoxycholic acid [3]. The enzyme can also hydroxylate the substrate at the 25 and 26 position, but to a lesser extent [1].
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CAS REGISTRY NUMBER
COMMENTARY
39369-22-7
-
440354-83-6
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
5beta-cholestane-3alpha,7alpha-diol + NADPH + O2
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
activation of farnesoid X receptor FXR initiates a feedback regulatory loop via induction of small heterodimer partner, SHP, which suppresses liver receptor homolog 1, LRH-1, and HNF4alpha dependent expression of sterol 12alpha hydroxylase, CYP8B1, overview
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
the enzyme is involved in bile acid synthesis, repression of bile acid synthesis and induction of basolateral bile acid export may represent adaptive mechanisms to limit bile acid burden in chronic cholestasis, but the changes do not sufficiently counteract cholestatic liver damage, overview
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
a key step in bile acid synthesis
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
thyroid hormone triiodothyronine has a regulatory function on the enzyme expressiona and bile acid metabolism, overview
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
-
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
dietary cholsterol and cholic acid have an influence of enzyme regulation
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
the enzyme channels bile acid precursors into cholic acid, but is not affected on mRNA and protein levels by increased cholic acid or reduced beta-muricholic acid levels, overview
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
the enzyme is necessary for the synthesis of cholic acid
-
-
?
additional information
?
-
-
bile acids repress human CYP8B1 transcription by reducing the transactivation activity of HNF4alpha through interaction of HNF4alpha with SHP and reduction of HNF4alpha expression in the liver
-
-
-
additional information
?
-
-
IL-1beta inhibits CYP8B1 gene transcription via a mitogen-activated protein kinase/c-Jun NH2-terminal kinase pathway that inhibits HNF4alpha gene expression and its DNA-binding ability. This mechanism may play an important role in the adaptive response to inflammatory cytokines and the protection of the liver during cholestasis
-
-
-
additional information
?
-
-
variation in the ratio between cholic acid and chenodeoxycholic acid in human bile are not due to polymorphisms in gene CYP8B1, overview
-
-
-
additional information
?
-
-
CYP8B1 is reportedly regulated by PPARalpha, overview
-
-
-
additional information
?
-
-
the enzyme expression is not affected by primary biliary cirrhosis
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
HNF4alpha directly binds to the promoter region of the mouse cyp8b1 and positively regulates its expression. CYP8B1 enzyme activity is absent in HNF4alphaDELTAL mice
-
-
-
additional information
?
-
-
sterol regulatory element binding proteins 1a and 1c enhance transcription of the CYP8B1 gene through binding to sterol regulatory element. Cholesterol loading reduces sterol regulatory element binding proteins 1 mRNA expression in addition to reducing functional sterol regulatory element binding proteins 1 protein, and results in decreasing CYP8B1 gene transcription
-
-
-
additional information
?
-
-
CYP8B1 is reportedly regulated by PPARalpha, overview
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
while Cyp8b1 repression by the nuclear bile acid receptor FXR is also intact in mice deficient for liver receptor homolog 1, LRH-1, in hepatocytes, basal CYP8B1 mRNA levels are significantly decreased and there are corresponding changes in the composition of the bile acid pool. Liver receptor homolog 1, LRH-1, is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
key enzyme of the bile acid biosynthetic pathway. It regulates the composition of bile acids in bile, i.e. ratio between cholic acid and chenodeoxycholic acid. Bile acids inhibit CYP8B1 gene transcription by inducing alpha-fetoprotein transcription factor and inhibiting HNF4alpha expression
-
-
-
additional information
?
-
-
specific enzyme required for cholic acid synthesis. The levels of this enzyme determine the ratio of cholic acid to chenodeoxycholic acid and thus the hydrophobicity of the circulating bile acid pool
-
-
-
additional information
?
-
-
sterol regulatory element binding proteins 1a and 1c enhance transcription of the CYP8B1 gene through binding to sterol regulatory element. Cholesterol loading reduces sterol regulatory element binding proteins 1 mRNA expression in addition to reducing functional sterol regulatory element binding proteins 1 protein, and results in decreasing CYP8B1 gene transcription
-
-
-
additional information
?
-
-
the enzyme is involved in bile acid synthesis, critical importance for the composition of bile acids formed in the liver, regulated by thyroid hormone at the mRNA level
-
-
-
additional information
?
-
-
the enzyme is required for biosynthesis of cholic acid. CYP8b1 is transcriptionally down-regulated by hydrophobic but not hydrophilic bile acids. Cholesterol feeding and a single thyroid hormone injection repress CYP8b1 in face of cholesterol 7alpha-hydroxylase specific activities
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
activation of farnesoid X receptor FXR initiates a feedback regulatory loop via induction of small heterodimer partner, SHP, which suppresses liver receptor homolog 1, LRH-1, and HNF4alpha dependent expression of sterol 12alpha hydroxylase, CYP8B1, overview
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
the enzyme is involved in bile acid synthesis, repression of bile acid synthesis and induction of basolateral bile acid export may represent adaptive mechanisms to limit bile acid burden in chronic cholestasis, but the changes do not sufficiently counteract cholestatic liver damage, overview
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
a key step in bile acid synthesis
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
5beta-cholestan-3alpha,7alpha-diol + NADPH + H+ + O2
5beta-cholestan-3alpha,7alpha,12alpha-triol + NADP+ + H2O
-
-
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
thyroid hormone triiodothyronine has a regulatory function on the enzyme expressiona and bile acid metabolism, overview
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
dietary cholsterol and cholic acid have an influence of enzyme regulation
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
the enzyme channels bile acid precursors into cholic acid, but is not affected on mRNA and protein levels by increased cholic acid or reduced beta-muricholic acid levels, overview
-
-
?
cholesterol + NADPH + O2
12-hydroxycholesterol + NADP+ + H2O
-
the enzyme is necessary for the synthesis of cholic acid
-
-
?
additional information
?
-
-
bile acids repress human CYP8B1 transcription by reducing the transactivation activity of HNF4alpha through interaction of HNF4alpha with SHP and reduction of HNF4alpha expression in the liver
-
-
-
additional information
?
-
-
IL-1beta inhibits CYP8B1 gene transcription via a mitogen-activated protein kinase/c-Jun NH2-terminal kinase pathway that inhibits HNF4alpha gene expression and its DNA-binding ability. This mechanism may play an important role in the adaptive response to inflammatory cytokines and the protection of the liver during cholestasis
-
-
-
additional information
?
-
-
variation in the ratio between cholic acid and chenodeoxycholic acid in human bile are not due to polymorphisms in gene CYP8B1, overview
-
-
-
additional information
?
-
-
CYP8B1 is reportedly regulated by PPARalpha, overview
-
-
-
additional information
?
-
-
the enzyme expression is not affected by primary biliary cirrhosis
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
HNF4alpha directly binds to the promoter region of the mouse cyp8b1 and positively regulates its expression. CYP8B1 enzyme activity is absent in HNF4alphaDELTAL mice
-
-
-
additional information
?
-
-
sterol regulatory element binding proteins 1a and 1c enhance transcription of the CYP8B1 gene through binding to sterol regulatory element. Cholesterol loading reduces sterol regulatory element binding proteins 1 mRNA expression in addition to reducing functional sterol regulatory element binding proteins 1 protein, and results in decreasing CYP8B1 gene transcription
-
-
-
additional information
?
-
-
CYP8B1 is reportedly regulated by PPARalpha, overview
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
while Cyp8b1 repression by the nuclear bile acid receptor FXR is also intact in mice deficient for liver receptor homolog 1, LRH-1, in hepatocytes, basal CYP8B1 mRNA levels are significantly decreased and there are corresponding changes in the composition of the bile acid pool. Liver receptor homolog 1, LRH-1, is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
key enzyme of the bile acid biosynthetic pathway. It regulates the composition of bile acids in bile, i.e. ratio between cholic acid and chenodeoxycholic acid. Bile acids inhibit CYP8B1 gene transcription by inducing alpha-fetoprotein transcription factor and inhibiting HNF4alpha expression
-
-
-
additional information
?
-
-
specific enzyme required for cholic acid synthesis. The levels of this enzyme determine the ratio of cholic acid to chenodeoxycholic acid and thus the hydrophobicity of the circulating bile acid pool
-
-
-
additional information
?
-
-
sterol regulatory element binding proteins 1a and 1c enhance transcription of the CYP8B1 gene through binding to sterol regulatory element. Cholesterol loading reduces sterol regulatory element binding proteins 1 mRNA expression in addition to reducing functional sterol regulatory element binding proteins 1 protein, and results in decreasing CYP8B1 gene transcription
-
-
-
additional information
?
-
-
the enzyme is involved in bile acid synthesis, critical importance for the composition of bile acids formed in the liver, regulated by thyroid hormone at the mRNA level
-
-
-
additional information
?
-
-
the enzyme is required for biosynthesis of cholic acid. CYP8b1 is transcriptionally down-regulated by hydrophobic but not hydrophilic bile acids. Cholesterol feeding and a single thyroid hormone injection repress CYP8b1 in face of cholesterol 7alpha-hydroxylase specific activities
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
additional information
?
-
-
the enzyme is involved in trihydroxy bile acid metabolism and cholic acid synthesis from cholesterol, overview
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
thyroid hormone triiodothyronine, i.e. T3, supresses enzyme expression in vivo
-
additional information
-
the enzyme expression is suppressed by cholesterol, bile acids, and insulin via activation of small heterodimer partner, a universal repressor, by ligand-bound farnesoid x receptor
-
additional information
-
feeding of cholic acid suppresses expression of CYP8B1, the effect is partly reversed by taurine, feeding of taurine alone has no effect on enzyme expression
-
additional information
-
the enzyme expression is suppressed by cholesterol, bile acids, and insulin via activation of small heterodimer partner, a universal repressor, by ligand-bound farnesoid x receptor
-
additional information
-
enzyme expression is repressed by the nuclear bile acid receptor FXR
-
additional information
-
feeding of cholic acid, taurine, or cholesterol does not affect expression of CYP8B1
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
hepatocyte nuclear factor 4a strongly induces the enzyme, the enzyme expression is induced by soybean isoflavones, e.g. genistein, daidzein, and glycitein, presence of PPARa inhibits isoflavone upregulation of CYP8B1 in cotransfected HepG2 cells, mechanism modeling, overview
-
additional information
-
feeding of taurine alone has no effect on enzyme expression
-
additional information
-
hepatocyte nuclear factor 4a strongly induces the enzyme, the enzyme expression is induced by soybean isoflavones, e.g. genistein, daidzein, and glycitein, in both female and male mice, intake of soy isoflavones plus fenofibrate does not increase CYP8B1 mRNA levels in females, whereas there was an obvious upregulation in males, presence of PPARa inhibits isoflavone upregulation of CYP8B1 in cotransfected HepG2 cells, mechanism modeling, overview
-
additional information
-
feeding of cholic acid, taurine, or cholesterol does not affect expression of CYP8B1
-
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
enzyme expression pattern within the liver architecture, zonal distribution pattern, overview
-
enzyme is expressed in a development-dependent fashion, expression appears restricted to the early fetal stages
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
no change in Cyp8b1 mRNA or protein expression at day 10 postpartum lactating dams
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression analysis in healthy livers and liver with primary biliary cirrhosis
-
expression analysis in response to soy bean isoflavones, transient expression in Hep-G2 cells
expression analysis, transcription factor G protein pathway suppressor 2, GPS2, affects CYP8B1 expression, mediated by direct interactions with LRH-1 and HNF4alpha, while the small heterodimer partner, SHP, does not affect the expression, Identification of a functional FXR response element in the human CYP8B1 promoter, regulation mechanism, overview
-
gene CYP8B1, expression analysis in liver tissues of wild-type, regulation of gene expression, overview
-
gene CYP8B1, genotyping of different strains of mice, e.g. C57BL/6J and CASA/Rk mice, and a hybrid of both
-
genetic structure and phylogenetic analysis
expression analysis in response to soy bean isoflavones, transient expression in Hep-G2 cells
-
expression analysis in response to soy bean isoflavones, transient expression in Hep-G2 cells
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
adenovirus-mediated gene transduction of retinoic acid-related orphan receptor alpha to mice strongly induces CYP8B1 expression (2.5fold)
-
CYP8B1 mRNA levels show a diurnal rhythm, decrease during the day and reaching the lowest levels 2 h into the dark cycle
-
dexamethasone administration results in significantly increased hepatic gene expression of Cyp8B1 in 2 days old rats compared with age-matched controls. In control animals, hepatic Cyp8b1 gene expression increases from 4 weeks onward and reaches to its maximal level at about 24 weeks of age
-
neonatal dexamethasone administration disturbs development of gene expression pattern into adulthood, the ratio of Cyp7a1/Cyp8b1 mRNA level, which is markedly increased at 4 weeks of age in the control group, shows a delayed increase at 8 weeks of age in the dexamethasone-treated animals
-
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
screening for genetic polymorphisms of gene CYP8B1, overview
additional information
-
construction of male CYP8B1 knockout mice, the mutant mice show increased cholesterol synthesis with normal diet, and decreased cholesterol absorption under cholesterol diet and feeding of cholic acid, they accumulate less cholesteryl esters compared to wild-type mice, phenotype, overview
additional information
-
construction of CYP8B1 null mice which show increased expression of cholesterol 7alpha-hydroxylase, CYP7A1, EC 1.14.13.17
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LINKS TO OTHER DATABASES (specific for EC-Number 1.14.13.96)
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