Information on EC 1.1.1.49 - glucose-6-phosphate dehydrogenase (NADP+)

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

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EC NUMBER
COMMENTARY hide
1.1.1.49
-
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RECOMMENDED NAME
GeneOntology No.
glucose-6-phosphate dehydrogenase (NADP+)
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
D-glucose 6-phosphate + NADP+ = 6-phospho-D-glucono-1,5-lactone + NADPH + H+
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
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reduction
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-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
formaldehyde oxidation I
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heterolactic fermentation
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NAD/NADP-NADH/NADPH cytosolic interconversion (yeast)
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pentose phosphate pathway (oxidative branch) I
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superpathway of glycolysis and the Entner-Doudoroff pathway
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pentose phosphate pathway
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Pentose phosphate pathway
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Glutathione metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
D-glucose-6-phosphate:NADP+ 1-oxidoreductase
The enzyme catalyses a step of the pentose phosphate pathway. The enzyme is specific for NADP+. cf. EC 1.1.1.363, glucose-6-phosphate dehydrogenase [NAD(P)+] and EC 1.1.1.388, glucose-6-phosphate dehydrogenase (NAD+).
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CAS REGISTRY NUMBER
COMMENTARY hide
9001-40-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
gene gsdA
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Manually annotated by BRENDA team
filamentous fungus isolated from infected tongue of a human patient
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Chalcalburnus tarischii Pallas
1811
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Manually annotated by BRENDA team
Chalcalburnus tarischii Pallas 1811
1811
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
subsp. lactofermentum
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Manually annotated by BRENDA team
subsp. lactofermentum
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Manually annotated by BRENDA team
Escherichia coli B / ATCC 11303
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Manually annotated by BRENDA team
high-level glucose-6-phosphate dehydrogenase strain
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
isolated from a sea water sample collected at the Terra Nova Bay, Ross Sea, Antarctica
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Manually annotated by BRENDA team
turkey
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Manually annotated by BRENDA team
and strain 124A
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Manually annotated by BRENDA team
and strain 124A
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
var. Samsun, resistant SNN cultivar and susceptible Xanthi cultivar
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Manually annotated by BRENDA team
cultivar Nipponbare
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Manually annotated by BRENDA team
Penicillium duponti
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
soil-isolate
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Manually annotated by BRENDA team
soil-isolate
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Manually annotated by BRENDA team
C
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Manually annotated by BRENDA team
C
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Manually annotated by BRENDA team
constitutive enzyme
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Manually annotated by BRENDA team
4 weeks-old plants, isozymes in plastid, P1 and P2, and cytosol
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
2 isoenzymes
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
427 strain
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
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development and optimization of a specific colorimetric assay whereby the NADPH generated reduces the tetrazolium salt WST-1, i.e 2-(4-indophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl-2H tetrazolium), to water-soluble yellow-colored formazan with 1-methoxy-5-methylphenazium methylsulfate as an electron carrier
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-deoxy-D-glucose 6-phosphate + NAD(P)+
2-deoxy-D-glucono-1,5-lactone 6-phosphate + NAD(P)H
show the reaction diagram
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low activity
-
-
?
2-deoxy-D-glucose 6-phosphate + NADP+
2-deoxy-D-glucono-1,5-lactone 6-phosphate + NADPH
show the reaction diagram
2-deoxy-D-glucose-6-phosphate + NADP+
2-deoxy-D-gluconate 6-phosphate + NADPH
show the reaction diagram
-
-
-
-
?
6-phosphonogluconate + NADPH
?
show the reaction diagram
D-galactose 6-phosphate + NAD(P)+
D-galactonate 6-phosphate + NADH
show the reaction diagram
D-glucose + NAD(P)+
D-gluconate + NAD(P)H
show the reaction diagram
-
activity only with dimethylsulfoxide added by 40% (v/v)
-
-
?
D-glucose 6-phosphate + deamino-NADP+
?
show the reaction diagram
D-glucose 6-phosphate + deamino-NADP+
D-glucono-1,5-lactone 6-phosphate + deamino-NADPH
show the reaction diagram
-
-
-
-
?
D-glucose 6-phosphate + H2O + NADP+
D-gluconate 6-phosphate + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NAD(P)+
D-glucono-1,5-lactone 6-phosphate + NAD(P)H
show the reaction diagram
D-glucose 6-phosphate + NAD+
6-phospho-D-glucono-1,5-lactone + NADH + H+
show the reaction diagram
D-glucose 6-phosphate + NAD+
6-phospho-D-glucono-1,5-lactone + NADP + H+
show the reaction diagram
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very low activity with NAD+
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-
?
D-glucose 6-phosphate + NAD+
D-glucono-1,5-lactone 6-phosphate + NADH + H+
show the reaction diagram
D-glucose 6-phosphate + NADP+
6-phospho-D-glucono-1,5-lactone + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NADP+
D-gluconate 6-phosphate + NADPH
show the reaction diagram
D-glucose 6-phosphate + NADP+
D-glucono-1,5-lactone 6-phosphate + NADPH
show the reaction diagram
D-glucose 6-phosphate + NADP+
D-glucono-1,5-lactone 6-phosphate + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NADP+
NADPH + ?
show the reaction diagram
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assay at pH 7.4
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-
?
D-glucose 6-phosphate + NADP+ + H2O
D-gluconate 6-phosphate + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + thio-NAD(P)+
D-glucono-1,5-lactone 6-phosphate + thio-NAD(P)H
show the reaction diagram
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the thio-cofactors give increased activity compared to the non-thio-cofactors
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-
?
deoxy-D-glucose 6-phosphate + NADP+
?
show the reaction diagram
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-
-
-
?
additional information
?
-
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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
D-glucose 6-phosphate + H2O + NADP+
D-gluconate 6-phosphate + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NAD(P)+
D-glucono-1,5-lactone 6-phosphate + NAD(P)H
show the reaction diagram
-
key enzyme catalyzing the first step of the pentose phosphate pathway generating NADPH for anabolic metabolsim pathways and protection systems in the liver
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-
?
D-glucose 6-phosphate + NADP+
6-phospho-D-glucono-1,5-lactone + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NADP+
D-glucono-1,5-lactone 6-phosphate + NADPH
show the reaction diagram
D-glucose 6-phosphate + NADP+
D-glucono-1,5-lactone 6-phosphate + NADPH + H+
show the reaction diagram
D-glucose 6-phosphate + NADP+ + H2O
D-gluconate 6-phosphate + NADPH + H+
show the reaction diagram
additional information
?
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
deamino-NADP+
thio-NAD+
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thio-NADP+
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best cofactor
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ag+
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1 mM, 1.6fold activation, G6PDH-2
Na2HPO4
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at 400 mM regains 22% activity on refolding
Na2SO4
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at 400 mM regains 23% activity on refolding
NaCl
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at 400 mM regains 63% activity on refolding
NaClO4
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at 400 mM regains 2.3% activity on refolding
NaSCN
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at 400 mM regains 1.4% activity on refolding
Ni2+
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about 110% activity at 5 mM (isoform G6PD2), about 115% activity at 2 mM (isoform G6PD1)
nitrate
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activates plastidic isozymes by 10fold by direct action on the enzyme
nitrite
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activates plastidic isozymes by 10fold by direct action on the enzyme
Sodium acetate
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at 400 mM regains 58% activity on refolding
sulfate
-
activates plastidic isozymes by 10fold by direct action on the enzyme
additional information
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
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(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
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(2S,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
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(2S,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
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(3alpha)-3,21-dihydroxypregnan-20-one
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(4Z)-4-(3-bromobenzylidene)-1-(4-methylphenyl)pyrazolidine-3,5-dione
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(5Z)-1-(4-bromophenyl)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]pyrimidine-2,4,6(1H,3H,5H)-trione
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(5Z)-1-(4-ethoxyphenyl)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]pyrimidine-2,4,6(1H,3H,5H)-trione
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(5Z)-5-[[5-(2-methyl-4-nitrophenyl)furan-2-yl]methylidene]-1-(3-methylphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
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reversible, non-competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
16-bromoepiandrosterone
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no activity at 0.03 mM
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2'-phosphoadenosine 5'-diphosphoribose
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2,3-diphosphoglycerate
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-
2-[(5Z)-5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoate
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2-[(E)-(4-nitrocyclohexa-2,4-dien-1-yl)(2-phenylhydrazinylidene)methyl]benzene-1,4-diol
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non-competitive inhibition versus NADP+, non-competitive or mixed-type versus D-glucose 6-phosphate
2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-5-methyl-4-(3,4,5-trimethoxybenzyl)-2,4-dihydro-3H-pyrazol-3-one
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irreversible, non-competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
3-(3,4-dichlorophenyl)-1,1'-dimethyl urea
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cytosolic isozyme, inhibition by uncoupling of photosynthetic electron transport
3-(4-hydroxyphenyl)-2-(pyridin-3-yl)quinazolin-4(3H)-one
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irreversible, non-competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
3-(5-bromopyridin-2-yl)-2-(pyridin-3-yl)quinazolin-4(3H)-one
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irreversible, non-competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
3-(5-[(E)-[2-(5-nitropyridin-2-yl)hydrazinylidene]methyl]furan-2-yl)benzoic acid
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4-fluoro-N-(4-hydroxynaphthalen-1-yl)benzenesulfonamide
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4-methyl-3-(propan-2-yloxy)-6H-benzo[c]chromen-6-one
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non-competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
5-(3alpha,7alpha,12alpha-triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide
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weak inhibition
5-(3alpha,7alpha,12alpha-trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide
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weak inhibition
5-[[5-(4-methoxy-2-nitrophenyl)furan-2-yl]methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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reversible, competitive inhibition versus NADP+, mixed-type versus D-glucose 6-phosphate
5alpha-androstan-16-alpha-bromo-3beta-ol-17-one
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in vitro cell viability assays shows a LD50 of 20 microM for Trypanosoma cruzi epimastigotes
5alpha-Androstan-3beta-ol-17-one
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uncompetitive inhibitor
5alpha-androsten-16-alpha-bromo-3beta-ol-17-one
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potent inhibitor, in vitro cell viability assays shows a LD50 of 12 microM for Trypanosoma cruzi epimastigotes
6-amino-NAD+
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irreversibly inhibits G6PD
6-amino-NADP+
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irreversibly inhibits G6PD
6-phosphogluconate
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adenosine 5' [beta,gamma-amido] triphosphate
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adenosine 5' [beta-thio] diphosphate
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adenosine 5' [gamma-thio] triphosphate
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-
amikacin
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in vitro, noncompetitive
ammonia
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inhibition in vitro and in vivo at sublethal concentration of 0.0022-0.0055 mM, IC50: 0.0187 mM
amoxicillin
Chalcalburnus tarischii Pallas
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-
beta-naphthoquinone-4-sulfonic acid
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1 mM, 68% inhibition, G6PDH-1; 1 mM, 81% inhibition, G6PDH-2
Blue dextran
-
-
-
Ca2+
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about 90% residual activity at 2 mM
ceftriaxone
-
strongly inhibits
chymotrypsin
-
-
-
Ciprofloxacin
Chalcalburnus tarischii Pallas
-
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cumene hydroperoxide
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1% residual activity after treatment with 17 mM cumene hydroperoxide at 50°C and pH 7 for 2 h
cycloheximide
-
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cypermethrin
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inhibits G6PD in vitro
D-glucose 6-phosphate
dehydroandrosterone
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uncompetitive inhibitor
dehydroepiandrosterone
deltamethrin
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inhibits G6PD both in vivo and in vitro, significantly inhibits activity after the 48th hour. Among pesticides, it is the most effective one, which is widely used both at homes and in agricultural fields. Deltamethrin inhibits the enzyme at very low doses, particularly in in vivo conditions, indicating that fish in natural and cultural environments are susceptible to this pesticide and that deltamethrin contaminations can be cause high mortality in fish population, which may lead to the increase in food insufficiency for increasing populations and cause disruption of ecological balance. Thus, usage of deltamethrin must be well controlled
dithiothreitol
-
about 40% inhibition at 5 mM
epiandrosterone
estrogen
-
-
Fe3+
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enzyme activities are significantly decreased in the presence of 30 and 300 ppm Fe3+
fructose 6-phosphate
-
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gentamicin sulfate
-
in vitro, noncompetitive
glucosamine
-
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glucosamine 6-phosphate
glucose
glyceraldehyde 3-phosphate
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-
glyoxylate
-
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guanidinium hydrochloride
guanosine hydrochloride
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the enzyme shows a sharp loss in activity above 0.75 M, but is activated by low concentrations of 0.2 M of GdmCl
hydrogen peroxide
-
inhibitory at 0.25%, at pH 7
isocitrate
-
-
KMnO4
Chalcalburnus tarischii Pallas
-
-
lidocaine
-
strongly inhibits
marcaine
-
noncompetitive
meloksikam
-
strongly inhibits
metamizol
MgSO4
-
competitive
N-(4-hydroxynaphthalen-1-yl)-2,5-dimethylbenzenesulfonamide
-
-
N-ethyl-N'-[(3alpha)-17-oxoandrostan-3-yl]urea
-
-
N-[(3alpha)-17-oxoandrostan-3-yl]sulfuric diamide
-
-
N-[(3alpha)-21-hydroxy-20-oxopregnan-3-yl]sulfuric diamide
-
-
NADP+
netilmicin
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inhibition of wild-type and mutant enzymes 1-3
Ni2+
-
about 95% residual activity at 2 mM
Nicotine
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inhibits the enzyme from lung, testis, kidney, stomach, and brain, in concert with vitamin E the enzyme from testis brain and liver is inhibited, tissue-specific inhibition of 12.5-48%, overview, nicotine has no effect on enzyme from muscle, heart, and liver
nidazole
Chalcalburnus tarischii Pallas
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-
oleic acid
-
G6PDH-1 is more susceptible to oleic acid than G6PDH-2
p-chloromercuribenzoate
palmitoyl-CoA
Pb2+
-
noncompetitive inhibition
penicillin G potassium
-
in vitro, noncompetitive
pental sodium
-
noncompetitive
peracetic acid
-
1% residual activity after treatment with 4 mM peracetic acid at 25°C and pH 7 for 15 min
phenylmethylsulfonyl fluoride
-
about 48% inhibition at 5 mM
phosphoenol pyruvate
-
25% inhibition at 10 mM
phosphoenolpyruvate
prilocaine
-
strongly inhibits
progesterone
-
-
propoxur
-
inhibits G6PD in vitro
pyridoxal 5'-phosphate
-
-
quartz
-
24 h incubation with quartz particles (80 microg/cm(2)) inhibits G6PD activity by 70%. Inhibition is fully prevented by glutathione. Silica exerts on G6PD an oxidative damage
-
Ribulose 1,5-diphosphate
-
-
RNAi
-
sodium ceftizoxime
-
inhibition of wild-type and mutant enzymes 1-3
sodium cefuroxime
-
inhibition of wild-type and mutant enzymes 1-3
streptomycin
-
inhibition of wild-type and mutant enzyme 3
sulfanilacetamide
Chalcalburnus tarischii Pallas
-
-
sulfanilamide
Chalcalburnus tarischii Pallas
-
-
suramin
-
77% inhibition at 0.05 mM
tert-butyl hydroperoxide
-
1% residual activity after treatment with 290 mM tert-butyl hydroperoxide at 50°C and pH 7 for 3 h
Thioredoxin f
-
from chloroplasts
-
Tl+
-
201Tl solution and radiation exposure has inhibitory effects on the enzyme activity both in vivo and in vitro
Trypsin
-
after 2 h of trypsin digestion in the presence of 0.01 mM NADP+ the enzyme retains about 57% of its original activity
-
Urea
-
inhibition in vitro and in vivo at sublethal concentration of 0.02-0.05 mM, IC50: 0.0238 mM
Vancomycin
vitamin E
-
in concert with nicotine the enzyme from testis brain and liver is inhibited, while the enzyme from muscle and stomach is activated, overview
additional information
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-(3alpha,12alpha-dihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide
-
weak activation
5-(3alpha,acetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide
-
activates
6-aminohexanoic acid
-
marginally increases the refolding yield in the presence of Arg, and it is unable to replace Arg in promoting a high refolding yield
acetazolamide
-
activates
anhydrotetracyclin
-
induces expression of mature G6PDH1
-
artesunate
-
induces a 25fold increase in glucose-6-phosphate dehydrogenase activity while there is no significant reduction in the red blood cell count. Critical role for glucose-6-phosphate dehydrogenase in the prevention of oxidative stress and lysis of red blood cells in artesunate-treated rats
ATP
-
isoform Zwf-2 is active in the presence of 3m MATP, and then only with NADP+ as a coenzyme
butanol
-
marginally increases the refolding yield in the presence of Arg, and it is unable to replace Arg in promoting a high refolding yield
cyclophilin A
-
facilitates refolding, the yield, at about 82%, is about 12% higher than without cyclophilin A. Even with 0.0004 mM cyclophilin A in the standard refolding buffer, maximal recovery takes about 7 days
-
dithiothreitol
-
dithiothreitol has major positive influence on refolding
glucosamine 6-phosphate
-
-
glycerol
-
marginally increases the refolding yield in the presence of Arg, and it is unable to replace Arg in promoting a high refolding yield
guanosine hydrochloride
-
the enzyme shows a sharp loss in activity above 0.75 M, but is activated by low concentrations of 0.2 M of GdmCl
H2O2
-
H2O2, produced under salt stress, induces increased G6PDH activity and the enzymes of glutathione cycle, which concomitantly results in an increased reduced glutathione contents
Insulin
-
stimulates, in pregnant women with types 1 diabetes insulin effect on the enzyme activity is lower than in the control. In the group of pregnant women with type 2 diabetes and gestational diabetes the effect of insulin is decreased as compared to control
-
insulin-like growth factor 1
-
stimulates, in pregnant women with types 1 diabetes effect of insulin-like growth factor 1 is absent. In the group of pregnant women with type 2 diabetes and gestational diabetes the effect of insulin-like growth factor 1 is decreased as compared to control
-
L-Arg
-
L-Arg has major positive influence on refolding. L-Arg is the key player in the refolding of human G6PD, preventing the aggregation of folding intermediate
metamizol
-
activation of mutant enzymes 1 and 2
N-ethylmaleimide
-
blocking the SH group leads to activation of rBmG6PD activity
paraquat
-
activates plastidic isozymes by 10fold by direct action on the enzyme, no activation of the cytosolic isozyme
PEG 3350
-
marginally increases the refolding yield in the presence of Arg, and it is unable to replace Arg in promoting a high refolding yield
-
relaxin
-
stimulates, in pregnant women with types 1 diabetes effect of relaxin is absent. In the group of pregnant women with type 2 diabetes and gestational diabetes the effect of relaxin is somewhat higher as compared to control
-
S-methyl 1,2,3-benzothiadiazole-7-carbothioate
-
treatment of fruits
spermidine
-
activation constant: 0.2 mM
streptomycin
-
activation of mutant enzymes 1 and 2
Sucrose
-
in wild-type seedlings G6PD5 and G6PD6 show small (1.7- and 2fold, respectively) but significant induction by sucrose
trehalose
-
marginally increases the refolding yield in the presence of Arg, and it is unable to replace Arg in promoting a high refolding yield
vitamin E
-
in concert with nicotine the enzyme from testis brain and liver is inhibited, while the enzyme from muscle and stomach is activated by 36% and 20%, respectively, overview
additional information
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.374 - 35
2-deoxy-D-glucose 6-phosphate
0.279 - 0.864
6-phosphonogluconate
0.031 - 0.051
D-galactose 6-phosphate
0.0021 - 50.7
D-glucose 6-phosphate
0.0156 - 3
deamino-NADP+
0.047 - 14.66
NAD+
0.000012 - 17.7
NADP+
0.014 - 0.023
NADPH
<