Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.1.1.153
-
RECOMMENDED NAME
GeneOntology No.
sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
ordered bi-bi mechanism, NADPH binds first and NADP+ releases last
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
active site structure
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
active site structure, substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin, stereospecific hydride transfer, mechanism, structure-function relationship, overview
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
enzyme also reduces carbonyl compounds of non-pteridine derivatives
Drosophila melanogaster Oregon R
-
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
-
-
-
-
L-erythro-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Folate biosynthesis
-
Metabolic pathways
-
tetrahydrobiopterin biosynthesis I
-
SYSTEMATIC NAME
IUBMB Comments
L-erythro-7,8-dihydrobiopterin:NADP+ oxidoreductase
This enzyme catalyses the final step in the de novo synthesis of tetrahydrobiopterin from GTP. The enzyme, which is found in higher animals and some fungi and bacteria, produces the erythro form of tetrahydrobiopterin. cf. EC 1.1.1.325, sepiapterin reductase (L-threo-7,8-dihydrobiopterin forming).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
AKR1B1
-
-
reductase, sepiapterin
-
-
-
-
sepiapterin reductase
-
-
SPR
-
-
-
-
SPR
Q17QK8
-
SR
Rattus norvegicus Sprague-Dawley
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9059-48-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
low activity
-
-
Manually annotated by BRENDA team
; complete ORF
SwissProt
Manually annotated by BRENDA team
axenic strain Ax2
-
-
Manually annotated by BRENDA team
Drosophila melanogaster Oregon R
strain Oregon R
-
-
Manually annotated by BRENDA team
gene SPR
-
-
Manually annotated by BRENDA team
wild-type C57BL/6J mice
-
-
Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
Phycomyces sp.
-
-
-
Manually annotated by BRENDA team
; female and male Wistar rats
-
-
Manually annotated by BRENDA team
; male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Donryu; Sprague-Dawley
-
-
Manually annotated by BRENDA team
expressed in Escherichia coli
-
-
Manually annotated by BRENDA team
male sprague-dawley rats; Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Donryu
Donryu
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
-
1'-hydroxy-2'-oxopropyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
show the reaction diagram
-
-
-, i.e. 1'-oxo-2'-D-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
show the reaction diagram
-
-
-, i.e. 1'-oxo-2'-D-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
show the reaction diagram
-
-, preferred substrate
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
show the reaction diagram
-
-, preferred substrate
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
show the reaction diagram
-
-
-, i.e. 1'-oxo-2'-L-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
show the reaction diagram
-
-
-, i.e. 1'-oxo-2'-L-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
1,2-cyclohexadione + NADPH
?
show the reaction diagram
-
-
-
-
?
1,2-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
1-phenyl-1,2-propanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
2,3-butanediol + NADP+
?
show the reaction diagram
-
-
-
-
?
2,3-dimethoxyl-1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
2,4-pentanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Q64105
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
in the reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding L-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
equilibrium lies much in favor of dihydrobiopterin formation
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
catalyzes the complete reduction of pyrovoyltetrahydropterin to tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Donryu
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-, terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-pyruvoyl tetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-, 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin is formed by an aldose reductase-like enzyme activity, not by SR
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
last step of the de novo tetrahydrobiopterin biosynthesis initiating from GTP
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
last step of the tetrahydrobiopterin biosynthesis, substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin, structure-function relationship
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
two reductive steps oxidizing NADPH
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
-
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
the cofactor for aromatic amino acid hydrolases in the biosynthesis of aromatc amino acids and dopamine
-
r
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
-
-
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
Q5XPX7
-
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
-
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
Q5XPX7
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
-
6-pyruvoyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
-
-
6-pyruvoyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
?
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
no synthesis of the D-isomer
-
?
9,10-phenanthrenequinone + NADP+
?
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
-
-
-
-
?
acetohexamide + NADPH
?
show the reaction diagram
-
-
-
-
?
acetoin + NADPH
?
show the reaction diagram
-
-
-
-
?
acetoin + NADPH
?
show the reaction diagram
-
0.003 mM NADPH oxidised per 30 min
-
-
?
acetophenone + NADPH
?
show the reaction diagram
-
-
-
-
?
benzil + NADPH
?
show the reaction diagram
-
-
-
-
?
benzil + NADPH
?
show the reaction diagram
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
benzylacetone + NADPH
?
show the reaction diagram
-
-
-
-
?
diacetyl + NADPH
?
show the reaction diagram
-
-
-
-
?
diacetyl + NADPH
?
show the reaction diagram
-
-
-
-
?
diacetyl + NADPH
?
show the reaction diagram
-
-
-
-
?
diacetyl + NADPH
?
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
?
diacetyl + NADPH
acetoin + NADP+
show the reaction diagram
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
dihydrotepidopterin + NADP+
?
show the reaction diagram
-
15% relative activity
-
-
?
isosepiapterin + NADPH
6-(1-hydroxypropyl)-dihydropterin + NADP+
show the reaction diagram
-
-
-
?
isosepiapterin + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
r
L-erythro-dihydrobiopterin + NADP+
?
show the reaction diagram
-
-
-
-
?
L-erythro-dihydroneopterin + NADP+
?
show the reaction diagram
-
D-isomer completely inactive, very slow activity, no activity with the D-isomer
-
-
r
L-threo-dihydrobiopterin + NADP+
?
show the reaction diagram
-
D-isomer 45% relative activity
-
-
r
L-threo-dihydroneopterin + NADP+
?
show the reaction diagram
-
-
-
-
-
L-threo-dihydroneopterin + NADP+
?
show the reaction diagram
-
D-isomer completely inactive, very slow activity, no activity with the D-isomer
-
-
r
lactoyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
-
lactoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
menadione + NADPH
?
show the reaction diagram
-
-
-
-
?
menadione + NADPH
?
show the reaction diagram
-
-
-
-
?
menadione + NADPH
?
show the reaction diagram
-
-
-
-
?
menadione + NADPH
?
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
?
methylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
methylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
p-nitrobenzaldehyde + NADPH
p-nitrobenzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
?
p-nitrobenzaldehyde + NADPH
p-nitrobenzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
?
p-quinone + NADPH
?
show the reaction diagram
-
-
-
-
?
phenylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
phenylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
phenylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
phenylglyoxal + NADPH
?
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
?
phenylpropanedione + NADPH
phenylpropan-2,3-diol + NADP+
show the reaction diagram
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
propiophenone + NADPH
?
show the reaction diagram
-
-
-
-
?
pyruvoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH
1'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
show the reaction diagram
-
best substrate
-
-
?
sepiapterin + NADPH
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-, Q5XPX7
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
Q17QK8
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
detailed product determination and analysis using fluorescent substrates, 7,8-dihydrobiopterin can be oxidized nonenzymatically to biopterin
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
i.e. 2-amino-4-hydroxy-6-lactyl-7,8-dihydropteridine, biosynthesis pathway, overview
i.e. 2-amino-4-hydroxy-6-(1',2'-dihydroxypropyl-)7,8-dihydropteridine, which is a substrate for biosynthesis of tetrahydrobiopterin, i.e. 6R-L-erythro-1',2'-dihydroxy-propyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine, an important component for controling the concentration of catecholamines or indoleamines in the brain and other nerve tissues
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
sepiapterin reductase activity
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
cellular uptake of sepiapterin across the cell membrane results in an efficient accumulation of tetrahydrobiopterin, sepiapterin relocates across the plasma membrane via two distinct paths, the slower path connects to the cytosolic compartment, overview
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
xanthopterin B2 + NADPH
6-(1',2'-dihydroxypropyl)-dihydrolumazine + NADP+
show the reaction diagram
-
-
-
?
xanthopterin-B2 + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
r
methylglyoxal + NADPH
?
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
?
additional information
?
-
-
enzyme is quite similar to general aldo-keto reductases, especially to carbonyl reductase
-
-
-
additional information
?
-
-
some monoketotestosterones show slight activity
-
-
-
additional information
?
-
-
not: 6-acetyl-7-methyldihydropterin
-
-
-
additional information
?
-
-
not: methylglyoxal, menadione
-
-
-
additional information
?
-
-
enzyme also catalyzes the isomerization of 6-1'-oxo-2'-hydroxypropyl tetrahydropterin (6-lactoyltetrahydropterin) to 6-1'-hydroxy-2'-oxopropyltetrahydropterin
-
-
-
additional information
?
-
-
product determination
-
-
-
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
-
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
-
additional information
?
-
-
important in the metabolism of tetrahydrobiopterin and sepiapterin
-
-
-
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
-
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
-
additional information
?
-
-
the enzyme is involved in the tetrahydrobiopterin biosynthesis
-
-
-
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
-
additional information
?
-
-
descending substrate preference: sepiapterin, lactoyltetrahydropterin, pyruvoyltetrahydropterin, 1'-hydroxy-2'-oxopropyltetrahydropterin
-
-
-
additional information
?
-
-
no activity with 6-acetyl-7-methyl-7,8-dihydropterin
-
-
-
additional information
?
-
-
substrate specificity, the enzyme also exhibits non-specific NADPH-dependent dicarbonyl reductase activity, overview
-
-
-
additional information
?
-
-
sepiapterin or dihydrobiopterin are the precursors of the tetrahydrobiopterin-salvage pathway, enzyme activity and pathway regulation in vivo, overview
-
-
-
additional information
?
-
-
tetrahydropteridines in Dictyostelium are associated with mitochondrial function, probably via direct protection against oxidative stress, tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis, sepiapterin reductase expression is increased in Parkinsons disease brain tissue
-
-
-
additional information
?
-
Rattus norvegicus Sprague-Dawley
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
-
additional information
?
-
-
product determination, quantitative in vivo assay and product determination
-
-
-
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
show the reaction diagram
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
show the reaction diagram
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
show the reaction diagram
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Q64105
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
equilibrium lies much in favor of dihydrobiopterin formation
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
-
catalyzes the complete reduction of pyrovoyltetrahydropterin to tetrahydrobiopterin
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Donryu
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Drosophila melanogaster Oregon R
-
-
-
-
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
-
6-pyruvoyl tetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
last step of the de novo tetrahydrobiopterin biosynthesis initiating from GTP
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
last step of the tetrahydrobiopterin biosynthesis
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
the cofactor for aromatic amino acid hydrolases in the biosynthesis of aromatc amino acids and dopamine
-
r
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
-
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
Q5XPX7
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
i.e. 2-amino-4-hydroxy-6-lactyl-7,8-dihydropteridine, biosynthesis pathway, overview
i.e. 2-amino-4-hydroxy-6-(1',2'-dihydroxypropyl-)7,8-dihydropteridine, which is a substrate for biosynthesis of tetrahydrobiopterin, i.e. 6R-L-erythro-1',2'-dihydroxy-propyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine, an important component for controling the concentration of catecholamines or indoleamines in the brain and other nerve tissues
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
cellular uptake of sepiapterin across the cell membrane results in an efficient accumulation of tetrahydrobiopterin, sepiapterin relocates across the plasma membrane via two distinct paths, the slower path connects to the cytosolic compartment, overview
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
no synthesis of the D-isomer
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
-
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
-
additional information
?
-
-
important in the metabolism of tetrahydrobiopterin and sepiapterin
-
-
-
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
-
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
-
additional information
?
-
-
the enzyme is involved in the tetrahydrobiopterin biosynthesis
-
-
-
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
-
additional information
?
-
-
sepiapterin or dihydrobiopterin are the precursors of the tetrahydrobiopterin-salvage pathway, enzyme activity and pathway regulation in vivo, overview
-
-
-
additional information
?
-
-
tetrahydropteridines in Dictyostelium are associated with mitochondrial function, probably via direct protection against oxidative stress, tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis, sepiapterin reductase expression is increased in Parkinsons disease brain tissue
-
-
-
additional information
?
-
Rattus norvegicus Sprague-Dawley
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
-
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
-
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD+
-
reverse reaction, one-fifth of that with NADP+
NADH
-
activity one-half that of NADPH
NADH
-
activity one-fourth of that with NADPH
NADPH
-
determination and analysis of the binding structure of NADPH and NADP+ to the enzyme, overview
NADPH
Q17QK8
-
NADPH
-
NADPH-dependent enzyme
additional information
-
the enzyme does not contain flavin
-
additional information
-
does not show any activity with NADH
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,2-naphthoquinone
-
-
1-norepinephrine
-
; 3 mM: 30% inhibition
2,4-Dinitrophenol
-
0.1 mM: 89% inhibition
2,4-Dinitrophenol
-
37% inhibition of the reductive reaction at 0.01 mM; slight
2,4-Dinitrophenol
-
-
6,7-Diethylpterin-H2
-
-
6,7-dimethyldihydropterin
-
0.05 mM: 70% inhibition
6,7-dimethyllumazine
-
slight
6,7-dimethylpterin
-
0.05 mM: 46% inhibition; 46% inhibition of the reductive reaction at 0.05 mM
6,7-dimethylpterin-H2
-
70% inhibition of the reductive reaction at 0.05 mM
6-Carboxypterin
-
77% inhibition of the reductive reaction at 0.05 mM; IC50 0.014 mM, 0.05 mM: 77% inhibition
6-Carboxypterin
-
-
6-Carboxypterin
-
IC50 0.03 mM
6-Hydroxymethylpterin
-
0.05 mM: 23% inhibition; 23% inhibition of the reductive reaction at 0.05 mM
6-methyldihydropterin
-
0.05 mM: 59% inhibition
6-methylpterin
-
10% inhibition of the reductive reaction at 0.05 mM; slight
6-Methylpterin-H2
-
59% inhibition of the reductive reaction at 0.05 mM
7-Methylpterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
9,10-phenanthrenequinone
-
-
acetic acid
-
IC50 0.45 mM, pH 6.5
acetic acid
-
buffers that contain acetate inhibit activity
alpha-ketoglutarate
-
slight, IC50 5 mM
Benzoic acid
-
0.03 mM: 40% inhibition; 40% inhibition of the reductive reaction at 0.03 mM
benzoquinone
-
-
biopterin
-
0.05 mM: 24% inhibition; 24% inhibition of the reductive reaction at 0.05 mM
biopterin-H2
-
31% inhibition of the reductive reaction at 0.05 mM
catecholamine
-
-
Cd2+
-
IC50 0.1 mM
Cd2+
-
1 mM inhibits entirely
Cibacron Blue 3G-A
-
IC50 0.01 mM
D,L-Lactic acid
-
0.03 mM, 20% inhibition
D-erythro-neopterin
-
14% inhibition of the reductive reaction at 0.05 mM
D-erythro-neopterin-H2
-
7% inhibition of the reductive reaction at 0.05 mM
dicoumarol
-
IC50 0.0006 mM
dicoumarol
-
-
dihydrobiopterin
-
0.05 mM: 31% inhibition
dihydrobiopterin
-
-
dihydrobiopterin
-
non-competitive with NADPH or sepiapterin as varying substrate
dihydroxanthopterin
-
slight
DL-lactic acid
-
20% inhibition of the reductive reaction at 0.03 mM
dopamine
-
slight; slight inhibition
Ethacrynic acid
-
IC50 0.03 mM
Fe3+
-
1 mM inhibits entirely
-
formic acid
-
slight
Hg2+
-
IC50 0.00009 mM
Indomethacin
-
IC50 0.06 mM
Indomethacin
-
-
iodoacetate
-
72% inhibition of the reductive reaction at 0.1 mM
Isosepiapterin
-
83% inhibition of the reductive reaction at 0.05 mM; IC50 0.0065 mM, 0.05 mM: 83% inhibition
Isoxanthopterin
-
0.05 mM: very slight
KCN
-
25% inhibition of the reductive reaction at 2.5 mM; slight
L-erythro-dihydroneopterin
-
0.05 mM: 29% inhibition, D-isomer: slight inhibition
-
L-Erythro-neopterin
-
0.05 mM: 21% inhibition, D-isomer: slight inhibition; 21% inhibition of the reductive reaction at 0.05 mM
L-Erythro-neopterin-H2
-
29% inhibition of the reductive reaction at 0.05 mM
Leucopterin
-
0.05 mM: 21% inhibition; 21% inhibition of the reductive reaction at 0.05 mM
Melatonin
-
3 mM, almost complete inhibition; strong inhibition
Melatonin
-
very slight
Melatonin
-
-
N-acetyl-L-noradrenaline
-
weak inhibitor, N-acetyl-L-adrenaline does not bind enzyme
N-acetyl-p-tyramine
-
weak, N-acetyl-m-tyramine shows strong inhibition
N-acetyl-serotonin
-
complete inhibition
N-acetyldopamine
-
very slight
N-acetyldopamine
-
potent competitive inhibitor
N-acetyldopamine
-
noncompetitive
N-acetylphenethylamine
-
weak
N-acetylserotonin
-
0.05 mM, 90% inhibition of enzyme from stimulated mononuclear blood cells
N-acetylserotonin
-
IC50 0.0006 mM
N-acetylserotonin
-
3 mM, complete inhibition
N-acetylserotonin
-
very slight
N-acetylserotonin
-
potent competitive inhibitor
N-acetylserotonin
-
noncompetitive
N-acetylserotonin
-
-
N-acetylserotonin
Q64105
-
N-acetylserotonin
-
-
N-acetylserotonin
-
activity is completely inhibited by the addition of 0.5 mM N-acetylserotonin
N-acetylserotonin
-
-
N-acetylserotonin
-
-
N-acetyltryptamine
-
slight, N-acetyltryptophan does not bind enzyme
n-butyric acid
-
IC50 0.032 mM, pH 6.5
N-chloroacetyldopamine
-
strong inhibitor
N-chloroacetylserotonin
-
strong competitive inhibitor
N-chloroserotonin
Q64105
strong inhibitor
N-ethylmaleimide
-
-
N-lactoyldopamine
-
potent inhibitor
N-methoxyacetylserotonin
-
strong competitive inhibitor
N-methoxyacetylserotonin
-
noncompetitive
N-methoxyacetylserotonin
Q64105
strong competitive inhibitor
N-pyruvoyldopamine
-
potent inhibitor
n-valeric acid
-
IC50 0.25 mM, pH 6.5
NADP+
-
competitive inhibition at fixed concentration with varied NADPH, noncompetitive with varied sepiapterin
NADPH
-
above 0.1 mM
NADPH
-
product inhibition, with more than 0.1 mM, with 0.05 mM sepiapterin
NADPH
-
more than 0.05 mM causes substrate inhibition
NaN3
-
15% inhibition of the reductive reaction at 5 mM; slight
NEM
-
35% inhibition of the reductive reaction at 0.1 mM, 88% at 1 mM
oxaloacetate
Q64105
-
p-chloromercuribenzoate
-
-
p-mercuribenzoate
-
0.1 mM, 93% inhibition
PCMB
-
93% inhibition of the reductive reaction at 0.01 mM
Phenobarbital
-
slight, IC50 0.6 mM
phenylquinone
-
-
-
Propionamide
-
0.03 mM, 14% inhibition; 14% inhibition of the reductive reaction at 0.03 mM
Propionic acid
-
43% inhibition of the reductive reaction at 0.03 mM; IC50 0.0045 mM, pH 6.5
Propionic acid
-
IC50 0.3 mM, pH 6.4
pterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
pyrazole
-
slight, IC50 1 mM
Pyruvic acid
-
9% inhibition of the reductive reaction at 0.03 mM; slight
rutin
-
IC50 0.06 mM
sepiapterin
-
above 0.05 mM
sepiapterin
-
product inhibition, with more than 0.05 mM, with 0.1 mM NADPH
Sn2+
-
1 mM inhibits entirely
Sodium acetate
-
-
Xanthopterin
-
slight
Xanthopterin B2
-
slight
Xanthopterin-B2
-
12% inhibition of the reductive reaction at 0.05 mM
xanthopterin-H2
-
9% inhibition of the reductive reaction at 0.05 mM
Zn2+
-
IC50 0.4 mM
monoiodoacetate
-
-
additional information
-
other unconjugated pteridines, e.g. xanthopterin, that cause slight inhibition of enzymatic reduction
-
additional information
-
no inhibition by 1-epinephrine, phenylalanine, tyrosine, L-DOPA, L-tryptophan, L-5-hydroxy-tryptophan
-
additional information
-
inhibition by specific antibody from rabbits
-
additional information
-
Li+, Na+, Co2+, Mn2+, Ni2+ show slight inhibition at 1 mM
-
additional information
-
the enzyme activity is not affected by laminar shear stress in endothelial cells, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
the enzyme activity is not affected by laminar shear stress in endothelial cells, overview
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.007
-
1'-hydroxy-2'-oxopropyltetrahydropterin
-
pH 7.4, 37C
-
0.0021
-
1,2-naphthoquinone
-
wild-type, pH 6.4, 37C
0.027
-
1,4-Naphthoquinone
-
wild-type, pH 6.4, 37C
0.118
-
1-phenyl-1,2-propanedione
-
cofactor NADH
0.086
-
2,3-dimethoxyl-1,4-naphthoquinone
-
wild-type, pH 6.4, 37C
-
5.19
-
2,4-Pentanedione
-
-
0.0143
-
2-amino-6-(2-hydroxypropanoyl)pteridin-4(1H)-one
-
pH 6.4, 25C
0.0077
-
7,8-dihydrobiopterin
-
pH 10.4, 25C
0.00082
-
9,10-phenanthrene quinone
-
-
0.0019
-
9,10-phenanthrenequinone
-
mutant D257H, pH 6.4, 37C
0.0032
-
9,10-phenanthrenequinone
-
mutant S157A, pH 6.4, 37C
0.0088
-
9,10-phenanthrenequinone
-
wild-type, pH 6.4, 37C
0.0133
-
9,10-phenanthrenequinone
-
mutant M205G, pH 6.4, 37C
0.0196
-
9,10-phenanthrenequinone
-
mutant Y259A, pH 6.4, 37C
0.027
-
9,10-phenanthrenequinone
-
mutant K174L, pH 6.4, 37C
0.0501
-
9,10-phenanthrenequinone
-
mutant G14S, pH 6.4, 37C; mutant R42G, pH 6.4, 37C
0.116
-
9,10-phenanthrenequinone
-
mutant DELTA257-261, pH 6.4, 37C
0.126
-
9,10-phenanthrenequinone
-
mutant N99A, pH 6.4, 37C
0.464
-
9,10-phenanthrenequinone
-
mutant G18D, pH 6.4, 37C
29
-
acetoin
-
-
1.1
-
acetophenone
-
-
0.0183
-
benzil
-
-
0.02
-
benzil
-
pH 6.4, 25C
0.043
-
benzylacetone
-
-
1
-
Diacetyl
-
; pH 6.4, 25C
1.02
-
Diacetyl
-
cosubstrate NADH
0.057
-
dihydrobiopterin
-
at pH 10.4
0.008
-
lactoyltetrahydropterin
-
pH 7.4, 37C
0.0872
-
menadione
-
wild-type, pH 6.4, 37C
0.18
-
menadione
-
-
0.0057
-
NADP+
-
pH 10.4, 25C
0.077
-
NADP+
-
at pH 10.4
0.0014
-
NADPH
-
pH 10.4, 25C
0.0017
-
NADPH
-
-
0.006
-
NADPH
-
-
0.014
-
NADPH
-
-
0.43
-
p-nitrobenzaldehyde
-
-
0.75
-
p-quinone
-
-
0.59
-
Phenylglyoxal
-
-
0.0218
-
phenylpropanedione
-
; pH 6.4, 25C
0.14
-
propiophenone
-
-
0.002
-
pyruvoyltetrahydropterin
-
pH 7.4, 37C
0.00018
-
sepiapterin
-
wild type enzyme
0.00072
-
sepiapterin
-
mutant enzyme F99A
0.0016
-
sepiapterin
-
mutant enzyme W196A
0.0021
-
sepiapterin
-
pH 10.4, 25C
0.009
-
sepiapterin
-
pH 7.4, 37C
0.015
-
sepiapterin
-
-
0.02
-
sepiapterin
-
-
0.021
-
sepiapterin
-
-
0.021
-
sepiapterin
-
-
0.025
-
sepiapterin
-
mutant Y259A, pH 6.4, 37C; wild-type, pH 6.4, 37C
0.0283
-
sepiapterin
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37C
0.04
-
sepiapterin
-
-
0.041
-
sepiapterin
-
at pH 6.0
0.045
-
sepiapterin
-
mutant R42G, pH 6.4, 37C
0.0503
-
sepiapterin
-
mutant S157A, pH 6.4, 37C
0.0606
-
sepiapterin
-
mutant D257H, pH 6.4, 37C
0.075
-
sepiapterin
-
-
0.094
-
sepiapterin
-
mutant N99A, pH 6.4, 37C
0.133
-
sepiapterin
-
mutant M205G, pH 6.4, 37C
0.153
-
sepiapterin
-
estimated
0.169
-
sepiapterin
-
mutant K174L, pH 6.4, 37C
4.4
-
Methylglyoxal
-
-
additional information
-
additional information
-
kinetics
-
additional information
-
additional information
-
kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.627
-
1,2-naphthoquinone
-
wild-type, pH 6.4, 37C
0.45
-
1,4-Naphthoquinone
-
wild-type, pH 6.4, 37C
1.43
-
2,3-dimethoxyl-1,4-naphthoquinone
-
wild-type, pH 6.4, 37C
-
0.0048
-
9,10-phenanthrenequinone
-
mutant S157A, pH 6.4, 37C
0.0056
-
9,10-phenanthrenequinone
-
mutant G14S, pH 6.4, 37C
0.0058
-
9,10-phenanthrenequinone
-
mutant DELTA257-261, pH 6.4, 37C
0.027
-
9,10-phenanthrenequinone
-
mutant K174L, pH 6.4, 37C
0.048
-
9,10-phenanthrenequinone
-
mutant G18D, pH 6.4, 37C
0.098
-
9,10-phenanthrenequinone
-
mutant R42G, pH 6.4, 37C
0.107
-
9,10-phenanthrenequinone
-
mutant D257H, pH 6.4, 37C
0.146
-
9,10-phenanthrenequinone
-
wild-type, pH 6.4, 37C
0.22
-
9,10-phenanthrenequinone
-
mutant M205G, pH 6.4, 37C
0.29
-
9,10-phenanthrenequinone
-
mutant N99A, pH 6.4, 37C
0.627
-
9,10-phenanthrenequinone
-
wild-type, pH 6.4, 37C
0.805
-
9,10-phenanthrenequinone
-
mutant Y259A, pH 6.4, 37C
1.45
-
menadione
-
wild-type, pH 6.4, 37C
0.0053
-
sepiapterin
-
mutant N99A, pH 6.4, 37C
0.0058
-
sepiapterin
-
mutant S157A, pH 6.4, 37C
0.053
-
sepiapterin
-
mutant R42G, pH 6.4, 37C
0.09
-
sepiapterin
-
mutant K174L, pH 6.4, 37C
0.156
-
sepiapterin
-
mutant D257H, pH 6.4, 37C
0.428
-
sepiapterin
-
mutant M205G, pH 6.4, 37C
0.6
-
sepiapterin
-
mutant Y259A, pH 6.4, 37C
1.61
-
sepiapterin
-
wild-type, pH 6.4, 37C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.1
-
1-norepinephrine
-
pH 6.4, 25C, erythrocyte enzyme
3.4
-
1-norepinephrine
-
pH 6.4, 25C, brain enzyme
0.0009
-
benzoquinone
-
wild-type, pH 6.7, 37C
0.0027
-
Indomethacin
-
wild-type, pH 6.7, 37C
0.025
-
Melatonin
-
pH 6.4, 25C, erythrocyte enzyme
0.03
-
Melatonin
-
pH 6.4, 25C, brain enzyme
0.00017
-
N-acetyl-serotonin
-
pH 6.4, 25C, erythrocyte enzyme
0.0002
-
N-acetyl-serotonin
-
pH 6.4, 25C, brain enzyme
0.0009
-
N-acetylserotonin
-
wild-type, pH 6.7, 37C
0.0005
-
phenylquinone
-
wild-type, pH 6.7, 37C
-
2.3
-
serotonin
-
pH 6.4, 25C, brain enzyme
2.5
-
serotonin
-
pH 6.4, 25C, erythrocyte enzyme
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0089
-
1,2-naphthoquinone
-
wild-type, pH 6.7, 37C
0.014
-
6-Carboxypterin
-
IC50 0.014 mM, 0.05 mM: 77% inhibition
0.03
-
6-Carboxypterin
-
IC50 0.03 mM
0.0036
-
9,10-phenanthrenequinone
-
wild-type, pH 6.7, 37C
0.45
-
acetic acid
-
IC50 0.45 mM, pH 6.5
5
-
alpha-ketoglutarate
-
slight, IC50 5 mM
0.0028
-
benzoquinone
-
wild-type, pH 6.7, 37C
0.1
-
Cd2+
-
IC50 0.1 mM
0.01
-
Cibacron Blue 3G-A
-
IC50 0.01 mM
0.0002
-
dicoumarol
-
wild-type, pH 6.7, 37C
0.0006
-
dicoumarol
-
IC50 0.0006 mM
0.03
-
Ethacrynic acid
-
IC50 0.03 mM
0.00009
-
Hg2+
-
IC50 0.00009 mM
0.0081
-
Indomethacin
-
wild-type, pH 6.7, 37C
0.06
-
Indomethacin
-
IC50 0.06 mM
0.0065
-
Isosepiapterin
-
IC50 0.0065 mM, 0.05 mM: 83% inhibition
0.1
-
Melatonin
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37C
0.0006
-
N-acetylserotonin
-
IC50 0.0006 mM
0.0026
-
N-acetylserotonin
-
wild-type, pH 6.7, 37C
0.2
-
N-acetylserotonin
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37C
0.032
-
n-butyric acid
-
IC50 0.032 mM, pH 6.5
0.25
-
n-valeric acid
-
IC50 0.25 mM, pH 6.5
0.6
-
Phenobarbital
-
slight, IC50 0.6 mM
0.0016
-
phenylquinone
-
wild-type, pH 6.7, 37C
-
0.0045
-
Propionic acid
-
IC50 0.0045 mM, pH 6.5
0.3
-
Propionic acid
-
IC50 0.3 mM, pH 6.4
1
-
pyrazole
-
slight, IC50 1 mM
0.06
-
rutin
-
IC50 0.06 mM
0.4
-
Zn2+
-
IC50 0.4 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.022
-
-
measured in female flies, value lower in males
0.93
-
-
-
1.7
-
-
in Escherichia coli HB101, transformed with pBLY1 containing sepiapterin reductase cDNA
1.8
-
-
pH 6.7, 37C
9.76
-
-
-
additional information
-
-
purified enzyme
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
in potassium phosphate buffer
5.5
-
-
for reduction of sepiapterin; in potassium phosphate buffer
5.5
-
-
in potassium phosphate buffer
5.5
-
-
most active, sodium phosphate buffer
6.4
-
-
substrate reduction reaction, assay at
6.4
-
-
assay at, sepiapterin reductase activity
6.4
-
-
assay at
6.4
-
-
assay at
6.5
-
-
assay at
6.8
-
-
assay at, NADPH-dependent dicarbonyl reductase activity
6.8
-
-
assay at
7.4
-
-
assay at
8.6
-
-
optimum of isomerization of 6-1'-oxo-2'-hydroxypropyl(6-lactoyltetrahydropterin) to 6-1'-hydroxy-2'-oxopropyltetrahydropterin
8.8
-
-
in Tris-HCl buffer or in glycine-NaOH buffer
10.4
-
-
substrate oxidation reaction, assay at; the reverse reaction, oxidation of 7,8-dihydrobiopterin, activity rises with rise of pH
10.4
-
-
substrate oxidation reaction, assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
7.4
-
pH 5.5: optimum, pH 7.4: in 50 mM Tris-HCl buffer about 80% of maximum activity observed
5.7
6.7
-
optimium for activity, highest activity in phosphate buffer
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
30
-
assay at
25
-
-
assay at, sepiapterin reductase activity
25
-
-
assay at
37
-
-
assay at, NADPH-dependent dicarbonyl reductase activity
37
-
-
assay at
37
-
-
assay at
50
-
-
highest activity, activity decreases slowly above
50
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
adrenal medulla
Manually annotated by BRENDA team
-
mononuclear, cell culture
Manually annotated by BRENDA team
Rattus norvegicus Donryu, Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
; in all parts of the brain
Manually annotated by BRENDA team
-
sepiapterin reductase expression is increased in Parkinsons disease brain tissue
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
; in all parts of the brain
-
Manually annotated by BRENDA team
-
monoaminergic field, neurons
Manually annotated by BRENDA team
-
post-mortem semi-quantitative expression analysis in brain of control individuals and Parkinson disease patients, SPR expression is increased in Parkinson patients, but not in the other genes involved in the tetrahydrobiopterin biosynthesis, overview
Manually annotated by BRENDA team
-
pyramidal neurons
Manually annotated by BRENDA team
Rattus norvegicus Donryu
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
;
-
Manually annotated by BRENDA team
-
amniotic, cell culture
Manually annotated by BRENDA team
-
dermal, cell culture
Manually annotated by BRENDA team
Rattus norvegicus Donryu, Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
dorsal and ventral parts
Manually annotated by BRENDA team
-
no enzyme detectable
Manually annotated by BRENDA team
-
cell culture model for catecholaminergic neurons
Manually annotated by BRENDA team
additional information
-
tissue distribution, no activity in stomach, small intestine, and muscle, overview
Manually annotated by BRENDA team
additional information
-
not in leukocytes and ascites tumor cells
Manually annotated by BRENDA team
additional information
-
SR gene expression and activity in different developmental stages
Manually annotated by BRENDA team
additional information
-
SR gene expression and activity in different developmental stages
-
Manually annotated by BRENDA team
additional information
Rattus norvegicus Donryu, Rattus norvegicus Sprague-Dawley
-
not in leukocytes and ascites tumor cells
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
92% of total activity
Manually annotated by BRENDA team
additional information
-
intracellular localization, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
28000
-
-
SDS-PAGE
29200
-
-
calculated from amino acid sequence
30000
-
-
SDS-PAGE
39000
-
-
gel filtration, nondissociating PAGE
45300
-
-
gel filtration
55000
-
-
gel filtration
55000
-
-
gel filtration
56000
-
-
second band in SDS-PAGE
56000
-
-
Western blot analysis with polyclonal rabbit-antiserum
59000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 56000, SDS-PAGE
?
-
x * 29969, determined by cDNA sequence; x * 30000, Western blot analysis of native enzyme from crude cell extract; x * 32372, SDS-PAGE, includes His-tag residues
homodimer
-
2 * 27500, SDS-PAGE
homodimer
-
2 * 28000, SDS-PAGE, Western blot analysis with polyclonal rabbit-antiserum, determined by cDNA sequence
homodimer
-
2 * 26000, gradient SDS-PAGE
homodimer
-
2 * 29500
monomer
-
1 * 38400, SDS-PAGE
monomer
Drosophila melanogaster Oregon R
-
1 * 38400, SDS-PAGE
-
additional information
-
structure-function relationship, amino acid sequence comparison of several species
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified native and selenomethionine-labeled enzyme alone and in complex with NADP+ and sepiapterin, hanging drop vapour diffusion method, 18C, 0.004 ml protein solution, with or without 10 mM NADP+ and sepiapterin, is mixed with 0.001 ml of a mixture of 0.004 ml or reservoir solution containing 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, and 34% PEG 400, and 0.001 ml additive solution 1 M guanidinium hydrochloride, X-ray diffraction structure determination and analysis at 2.1 A and 1.7 A resolution, respectively
-
purified native and selenomethionine-labeled enzyme, hanging drop vapour diffusion microbatch method, 18C, 0.004 ml protein solution containing 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, is mixed with 0.001 ml of a mixture of 0.004 ml or reservoir solution containing 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, and 34% PEG 400, and 0.001 ml additive solution 1 M guanidinium hydrochloride, 2 days, X-ray diffraction structure determination and analysis at 2.1 A resolution
-
vapour diffusion technique
Q64105
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
unstable
5.5
-
-
pH 6.4 for enzyme assay; unstable
5.5
-
-
unstable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
50
-
relativley stable for 2 h in this range, loss of activity in 20 min at 70C
48
-
-
half of activity remains within 30 min
72
-
-
the melting temperature of the wild type enzyme is at 72.77C
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
bovine serum albumin stabilizes
-
NADP+ stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
20C, after ion exchange chromatography, no change in activity over one year of storage
-
-70C, in 20 mM Tris-HCl, pH 8.8
-
-70C, after dialyzation against Pipes, pH 7.5, 10% glycerol
-
-40C, in 50 mM potassium phosphate buffer, pH 6.9, at least stable for two months
-
-15C, in 150 mM Tris-HCl buffer, pH 6.0, second hydroxylapatite fraction, for 1 week, relatively little loss of activity
-
-15C, purified enzyme, 0.01 M potassium phosphate buffer, pH 6.0, stable for 1 week with little loss of activity
-
-70C, desalted extracts, several weeks without significant loss of activity
-
-80C, in 50 mM potassium phosphate buffer, 0,1 M KCl, pH 6.8
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
His GraviTrap nickel affinity column chromatography, gel filtration
-
Ni-NTA bead chromatography, MonoQ column chromatography, and Superdex 200 gel filtration
-
recombinant His-tagged native and selenomethionine-labeled enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, followed by gel filtration
-
recombinant protein using His-tag
-
recombinant protein using His-tag
Q5XPX7
liver; native enzyme 5000fold from liver by ammonium sulfate and protamine sulfate fractionation, and two times treatment by hydroxylapatite and anion exchange chromatography
-
liver, partially
-
recombinant protein using His-tag
-
recombinant protein of Escherichia coli
Q64105
; native enzyme from erythrocytes
-
; native enzyme from erythrocytes by hydroxylapatite and NADP+-affinity chromatography, to homogeneity
-
brain, partially, from erythrocytes to homogeneity; native enzyme partially from brain by ammonium sulfate fractionation and hydroxylapatite chromatography, and from erythrocytes to homogeneity by affinity chromatography and isoelectric focusing
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21 (DE3) cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21(DE3)/pLysS
-
expression of His-tagged native and selenomethionine-labeled enzyme in Escherichia coli strain BL21(DE3)
-
expressed in Escherichia coli BL21(DE3)/pLysS
-, Q5XPX7
recombinant protein expressed in Escherichia coli
-
chromosomal location 2p14-2p12, RT-PCR expression analysis
-
expressed in COS-7 and RNA-64A cells
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3, pLysS)
-
gene SPR, chromosomal location at 2p13, genomic structure, DNA and amino acid sequence determination of wild-type and mutant enzymes
-
recombinant protein expressed in Escherichia coli
Q64105
host cells transfected with sense, antisense and inverse antisense oligodeoxynucleotides
-
recombinant protein expressed in Escherichia coli
-
site-directed mutagenesis, recombinant protein expressed in Escherichia coli GI724
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
F99A
-
the mutant shows 3.9fold higher Km and lower Vmax (8.95%) than the wild type enzyme
D257H
-
mutant shows completely inhibited sepiapterin reduction. Mutation has only minimal effects on redox cycling
DELTA257-261
-
deletion of the C-terminal 5 amino acids almost completely eliminates enzyme activity. For redox cycling, the catalytic efficacy decreases to less than 1% of the wild type enzyme
G14S
-
mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
G18D
-
mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
K174L
-
catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
K251X
-
naturally occurring mutation in gene SPR, exon 3, causing enzyme deficiency
N99A
-
mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
P163L
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
Q119X
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150fs
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150G
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R42G
-
mutation leads to a 90% reduction in sepiapterin reduction activity and a 50% reduction in redox cycling activity. The catalytic efficiencies for this mutant decreases to 2% and 7% of wild type sepiapterin reductase for sepiapterin reduction and redox cycling, respectively
S157A
-
catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
K175I
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D/Y171V
-
double-point mutant does not show any activity towards any substrate
Y171V
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
W196A
-
the mutant shows 8.7fold higher Km and lower Vmax (5.64%) than the wild type enzyme
additional information
-
construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
additional information
-
construction of a mutant disrupted in the gene encoding sepiapterin reductase, the SR mutant produces about 3% of tetrahydropteridines compared to the wild-type and shows several functional defects related to mitochondria and oxidative stress, as retarded growth, poor spore viability, impaired mitochondrial function, and increased susceptibility to oxidative stress induced by hydroxylamine or cumene-hydroperoxide, overview. The physiological defects are almost completely rescued by extrachromosomal expression of the endogenous enzyme
additional information
-
construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
-
M205G
-
mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
additional information
-
identification of different mutant alleles or molecular lesions of enzymes, involved in the tetrahydrobiopterin metabolism, leading to disorders, SPR deficiency causes an autosomal recessive monoamine neurotransmitter deficiency, mutations occur in exons 2 and 3, in intron 2, and in the 5'-UTR, overview
additional information
-
a single nucleotide polymorphism around the SPR gene is involved in development of Parkonson's disease
Y259A
-
mutation of Tyr259, a unique potential phosphorylation site in the C-terminal substrate transfer motif, has no major effects on sepiapterin reduction and redox cycling activity
additional information
-
construction of enzyme knockout mice, the SPR null mice show partial lethality and highly reduced tetrahydrobiopterin content, e.g. less than 10% of wild-type levels in the brain, and monoamine contents. Spr-null mice exhibit severe monoamine deficiencies and a tremor-like phenotype after weaning, pteridine contents in the tissues of Spr mutant mice, phenotype, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder