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Information on EC 1.1.1.21 - aldose reductase and Organism(s) Bos taurus and UniProt Accession P16116
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1.1.1.21 aldose reductaseIUBMB Comments
Has wide specificity.
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Word Map
- 1.1.1.21
- lens
- nerve
- neuropathy
- sorbinil
- cataract
- mellitus
- retinopathy
- hyperglycemia
-
glycation
- streptozotocin
- galactose
-
sciatic
- fructose
- retinal
- endothelial
-
streptozotocin-induced
- myo-inositol
- erythrocyte
- reductases
-
nadph-dependent
-
streptozotocin-diabetic
-
microvascular
-
galactosemic
- galactitol
-
hypertonic
-
diabetes-induced
-
stz-induced
- opacity
-
antidiabetic
-
glucose-induced
-
osmolytes
- pericytes
-
nondiabetic
-
cataractogenesis
-
galactose-induced
- microangiopathy
-
endoneurial
- xylitol
-
sural
- hne
-
hyperglycemia-induced
- polyneuropathy
-
lenticular
-
glycaemic
-
mesangial
- synthesis
-
opacification
-
stz-diabetic
- alr
- akr1c3
- microaneurysms
- nutrition
- medicine
- drug development
- diagnostics
- biotechnology
The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
aldose reductase, akr1b10, akr1b3, akr1b, aldose reductase-like, aldose reductase-like protein, aldo-keto reductase family 1 member b1, akr1b14, aldose reductase 2, aldrxv4, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AKR1B1
20-alpha-HSD
-
-
-
-
20-alpha-hydroxysteroid dehydrogenase
-
-
-
-
aldehyde reductase
-
-
-
-
alditol:NADP 1-oxidoreductase
-
-
-
-
alditol:NADP oxidoreductase
-
-
-
-
aldo-keto reductase family 1 member B7
-
-
-
-
aldose xylose reductase
-
-
-
-
ALR2
Fibroblast growth factor regulated protein
-
-
-
-
FR-1 protein
-
-
-
-
MVDP
-
-
-
-
NADPH-aldopentose reductase
-
-
-
-
NADPH-aldose reductase
-
-
-
-
polyol dehydrogenase (NADP2)
-
-
-
-
TPN-polyol dehydrogenase
-
-
-
-
VAS deferens androgen-dependent protein
-
-
-
-
ALR2
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
alditol:NAD(P)+ 1-oxidoreductase
Has wide specificity.
CAS REGISTRY NUMBER
COMMENTARY
9028-31-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
alditol + NAD(P)+
aldose + NAD(P)H
-
-
-
-
r
pyridine-3-aldehyde + NAD(P)H
3-hydroxypyridine + NAD(P)+
-
low-KM enzyme subtype
-
-
r
xylitol + NAD(P)+
D-xylose + NAD(P)H + H+
-
-
-
-
r
D-glucose + NADPH + H+
D-sorbitol + NADP+
glucose free aldehyde is conceivably the form that is susceptible to the enzyme action
-
-
?
L-idose + NADPH + H+
alditol + NADP+
glucose free aldehyde is conceivably the form that is susceptible to the enzyme action
-
-
?
aldose + NAD(P)H
alditol + NAD(P)+
-
-
-
-
r
additional information
?
-
due to the unavoidable presence of the hemiacetal, glucose reduction by aldose reductase occurs under different conditions with respect to other relevant enzyme substrates, such as alkanals and alkenals, coming from membrane lipid peroxidation
-
-
?
additional information
?
-
-
due to the unavoidable presence of the hemiacetal, glucose reduction by aldose reductase occurs under different conditions with respect to other relevant enzyme substrates, such as alkanals and alkenals, coming from membrane lipid peroxidation
-
-
?
additional information
?
-
ability of the enzyme to interact and reduce highly hydrophilic and bulky substrates, substrate specificity an kinetics, overview
-
-
?
additional information
?
-
-
ability of the enzyme to interact and reduce highly hydrophilic and bulky substrates, substrate specificity an kinetics, overview
-
-
?
additional information
?
-
despite being claimed as an in vivo substrate of aldehyde reductase, D-glucose is not an ideal substrate for the enzyme. It displays a kcat comparable with other physiological and nonphysiological substrates. Glucose is poorly recognized by the enzyme with a measured KM ranging between 35 and 212 mM. L-idose, the C5 epimer of D-glucose, is a good substrate in studies on aldose reductase and for measurement of enzyme activity, as it mimics glucose and confirms the multitask nature of the catalytic site. L-Idose offers a much more suitable concentration of the free aldehyde form for activity measurements
-
-
?
additional information
?
-
-
despite being claimed as an in vivo substrate of aldehyde reductase, D-glucose is not an ideal substrate for the enzyme. It displays a kcat comparable with other physiological and nonphysiological substrates. Glucose is poorly recognized by the enzyme with a measured KM ranging between 35 and 212 mM. L-idose, the C5 epimer of D-glucose, is a good substrate in studies on aldose reductase and for measurement of enzyme activity, as it mimics glucose and confirms the multitask nature of the catalytic site. L-Idose offers a much more suitable concentration of the free aldehyde form for activity measurements
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
aldose + NAD(P)H
alditol + NAD(P)+
-
-
-
-
r
D-glucose + NADPH + H+
D-sorbitol + NADP+
glucose free aldehyde is conceivably the form that is susceptible to the enzyme action
-
-
?
additional information
?
-
due to the unavoidable presence of the hemiacetal, glucose reduction by aldose reductase occurs under different conditions with respect to other relevant enzyme substrates, such as alkanals and alkenals, coming from membrane lipid peroxidation
-
-
?
additional information
?
-
-
due to the unavoidable presence of the hemiacetal, glucose reduction by aldose reductase occurs under different conditions with respect to other relevant enzyme substrates, such as alkanals and alkenals, coming from membrane lipid peroxidation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(10-benzyl-3,4-dioxo-3,4-dihydro[1,2,4]triazino[4,3-a]benzimidazol-2(10H)-yl)acetic acid
-
(4S)-6-fluoro-2,3-dihydro-2'H,5'H-spiro[1-benzopyran-4,4'-imidazolidine]-2',5'-dione
-
1'-(4-chlorophenylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
1'-(4-methoxyphenylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
1'-(4-methylphenylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
1'-(9,10-dioxo-9,10-dihydroanthracen-2-ylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
1'-(naphthalen-2-ylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
2-(6-nitro-1,1,3-trioxo-1,3-dihydro-2H-1lambda~6~,2-benzothiazol-2-yl)propanoic acid
-
2-benzyl-1,3,3-trioxo-2,3-dihydro-1H-3lambda~6~-naphtho[1,2-d][1,2]thiazole-4-carboxylic acid
-
2-[(3,4-dihydroxyphenyl)methyl]-6-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one
-
3'-(4-chlorophenylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
3'-(4-methoxyphenylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
3'-(4-methylphenylsulfonyl)spiro[fluorene-9,50-imidazolidine]-2',4'-dione
-
3'-(9,10-dioxo-9,10-dihydroanthracen-2-ylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
3'-(naphthalen-2-ylsulfonyl)spiro[fluorene-9,5'-imidazolidine]-2',4'-dione
-
3-(4-nitro-1,1,3-trioxo-1,3-dihydro-2H-1lambda~6~,2-benzothiazol-2-yl)propanoic acid
-
3-(6-acetamido-1,1,3-trioxo-1,3-dihydro-2H-1lambda~6~,2-benzothiazol-2-yl)propanoic acid
-
3-[6-(3-methylbutanamido)-1,1,3-trioxo-1,3-dihydro-2H-1lambda~6~,2-benzothiazol-2-yl]propanoic acid
-
4-[(3-nitrophenyl)methyl]-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylic acid
-
[(2E)-2-[2-(carboxymethyl)hydrazinylidene]-3-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydro-1H-benzimidazol-1-yl](oxo)acetic acid
-
[(5Z)-5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
-
[3,4-dioxo-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4-dihydro[1,2,4]triazino[4,3-a]benzimidazol-2(10H)-yl]acetic acid
-
[5-methyl-7-oxo-4-(2-phenylethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl]acetic acid
-
(5-biphenyl-4-ylmethyl-2,4-dioxothiazolidin-3-yl)acetic acid methyl ester
-
15% inhibition of ALR2 at 0.05 mM
(5-biphenyl-4-ylmethylene-2,4-dioxothiazolidin-3-yl)-acetic acid
-
IC50: 0.00026 mM
(5-biphenyl-4-ylmethylene-2,4-dioxothiazolidin-3-yl)-acetic acid methyl ester
-
35% inhibition of ALR2 at 0.05 mM
(5-naphthalen-1-ylmethylene-2,4-dioxothiazolidin-3-yl)acetic acid
-
IC50: 0.00017 mM
(5-naphthalen-1-ylmethylene-2,4-dioxothiazolidin-3-yl)acetic acid methyl ester
-
12% inhibition of ALR2 at 0.05 mM
(Z)-5-(naphthalen-1-ylmethylidene)-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
52% inhibition at 0.025 mM
(Z)-5-(naphthalen-2-ylmethylidene)-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
59% inhibition at 0.025 mM
(Z)-5-[(3-hydroxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
-
(Z)-5-[(3-methoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
-
(Z)-5-[(3-phenoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
64% inhibition at 0.025 mM
(Z)-5-[(4-hydroxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
-
(Z)-5-[(4-methoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
-
(Z)-5-[(4-phenoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
-
(Z)-5-[(4-phenylphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
45% inhibition at 0.025 mM
1,5-bis(3,5-di-tert-butyl-4-hydroxyphenyl)-1,4-pentadiene-3-one
-
31.0% inhibition at 0.1 mM
2,5-bis(3,5-di-tert-butyl-4-hydroxybenzylidene)cyclopentanone
-
38.2% inhibition at 0.1 mM
2,6-bis(3,5-di-tert-butyl-4-hydroxybenzylidene)cyclohexanone
-
35.8% inhibition at 0.1 mM
2-[5-fluoro-2-methyl-1-p-(methylsulphinyl)benzylidine]indene-3-acetic acid
-
non-competitive
3,5-bis(3,5-di-tert-butyl-4-hydroxybenzylidene)-4-piperidone
-
29.2% inhibition at 0.1 mM
4-(5-biphenyl-4-ylmethylene-2,4-dioxothiazolidin-3-yl)-2-butenoic acid
-
21% inhibition of ALR2 at 0.05 mM
4-(5-biphenyl-4-ylmethylene-2,4-dioxothiazolidin-3-yl)-2-butenoic acid methyl ester
-
6% inhibition of ALR2 at 0.05 mM
4-[2,4-dioxo-5-(3-phenoxybenzylidene)thiazolidin-3-yl]-2-butenoic acid
-
19% inhibition of ALR2 at 0.05 mM
4-[2,4-dioxo-5-(3-phenoxybenzylidene)thiazolidin-3-yl]-2-butenoic acid methyl ester
-
25% inhibition of ALR2 at 0.05 mM
4-[2,4-dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl]-2-butenoic acid
-
57% inhibition of ALR2 at 0.05 mM
4-[5-(4-benzyloxybenzylidene)-2,4-dioxothiazolidin-3-yl]-2-butenoic acid methyl ester
-
23% inhibition of ALR2 at 0.05 mM
4-[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]-2-butenoic acid
-
IC50: 0.0042 mM
5-(4-benzyloxybenzylidene)-2,4-thiazolidinedione
-
10% inhibition of ALR2 at 0.05 mM
5-biphenyl-4-ylmethylene-2,4-thiazolidinedione
-
20% inhibition of ALR2 at 0.05 mM
8-bromo-4,4a-5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acid
-
4fold decreased inhibitory potency compared to the nonsubstituted parent compound
8-chloro-4,4a-5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acid
-
4fold decreased inhibitory potency compared to the nonsubstituted parent compound
8-methyl-4,4a-5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acid
-
2fold decreased inhibitory potency compared to the nonsubstituted parent compound
bisdemethoxycurcumin
-
i.e. 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0137 mM
Cu2+
-
oxidative inactivation of ALR2, ratio Cu2+ to enzyme of 2:1, precipitation of the enzyme occurs at higher Cu2+ concentration, alpha-crystallin stabilizes the enzyme and protects against inactivation and precipitation by Cu2+ with higher efficiency at 37°C compared to 25°C, overview
curcumin
-
i.e. 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0068 mM
demethoxycurcumin
-
i.e. 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0159 mM
disodium 4,6-dioxo-10-propyl-4H,6H-pyranol[3,2-g-]-quinoline-2,8-dicarboxylate
-
non-competitive
Mg2+
-
10 mM inhibits complex formation of ALR 2 with alpha-crystallin, induces ALR 2 aggregation and precipitation
thienocinnolinone alkanoic acid derivatives
-
i.e. 8-halogen-4,4a-5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acid derivatives, synthesis and inhibitory potency, IC50 as low as 0.0314 mM, the length of the N2 alkanoic chain strongly influences the inhibitory activity, overview
-
zofenoprilat-glutathione disulfide
-
the enzyme is specifically S-thionylated and inactivated by ZSSG, a homodisulfide formed by GSH and zofenoprilat, an angiotensin-converting enzyme inhibitor carrying a thiol group, which is more stable than glutathione, optimization, overview
[2,4-dioxo-5-(3-phenoxybenzyl)thiazolidin-3-yl]acetic acid methyl ester
-
26% inhibition of ALR2 at 0.05 mM
[2,4-dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl]acetic acid
-
IC50: 0.00082 mM
[2,4-dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl]acetic acid methyl ester
-
33% inhibition of ALR2 at 0.05 mM
[5-(3-aminobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid methyl ester
-
IC50: 0.039 mM
[5-(3-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
-
IC50: 0.00066 mM
[5-(3-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
43% inhibition of ALR2 at 0.05 mM
[5-(3-methoxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
IC50: 0.0211 mM
[5-(3-nitrobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid methyl ester
-
22% inhibition of ALR2 at 0.05 mM
[5-(4-aminobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid methyl ester
-
25% inhibition of ALR2 at 0.05 mM
[5-(4-benzyloxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
24% inhibition of ALR2 at 0.05 mM
[5-(4-benzyloxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
-
IC50: 0.00028 mM
[5-(4-benzyloxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
12% inhibition of ALR2 at 0.05 mM
[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
-
IC50: 0.00015 mM
[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
IC50: 0.0062 mM
[5-(4-methoxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
-
24% inhibition of ALR2 at 0.05 mM
[5-(4-nitrobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid methyl ester
-
8% inhibition of ALR2 at 0.05 mM
additional information
partial nonclassical competitive inhibition is exerted by the aldose hemiacetal on the reduction of the free aldehyde, aldose reductase modulation by hemiacetals, negative cooperative behavior of AR acting on L-idose, mechanism of inhibition, kinetic modelling, nonclassical competitive model, detailed overview
-
additional information
-
partial nonclassical competitive inhibition is exerted by the aldose hemiacetal on the reduction of the free aldehyde, aldose reductase modulation by hemiacetals, negative cooperative behavior of AR acting on L-idose, mechanism of inhibition, kinetic modelling, nonclassical competitive model, detailed overview
-
additional information
synthesis, characterization, hypoglycemic and aldose reductase inhibition activity of arylsulfonylspiro[fluorene-9,5-imidazolidine]-2,4-diones, analysis of the Kador-Sharpless model for minimal pharmacophoric requirements for an aldose reductase inhibitor, and superposition of target molecules on a hypoglycemic pharmacophoric model and a aldose reductase pharmacophoric model, overview. Molecular dynamics simulations and inhibitor binding model. Effects of the compounds on diabetic BALB/c mice
-
additional information
-
high ionic strength inhibits the enzyme to a higher extent when NADPH instead of NADH is used as a cofactor
-
additional information
-
molecular modelling, enzyme docking at the active site of the enzyme, structure-activity relationships of 5-arylidene-2,4-thiazolidinediones, an additional aromatic ring or an H-bond donor group on the 5-benzylidene ring enhance ALR2 inhibitory potency, the presence of a carboxylic anionic chain on N-3 is important, and the length of the carboxylic chain is critical, overview, no inhibition by 5b 4-[2,4-dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl]-2-butenoic acid methyl ester
-
additional information
-
no inhibition by 3,5-bis(3,4-dimethoxybenzylidene)-4-piperidone, 1,5-bis(3,4-dimethoxyphenyl)-1,4-pentadiene-3-one, 2,5-bis(3,4-dimethoxybenzylidene)cyclopentanone, and 2,6-bis(3,4-dimethoxybenzylidene)cyclohexanone, at 0.1 mM
-
additional information
-
poor inhibition by [2,4-dioxo-5-(4-phenoxybenzyl)thiazolidin-3-yl]acetic acid methyl ester
-
additional information
-
synthesis and evaluation of 2,4-thiazolidinedione inhibitors, structure-activity relationships, overview. No inhibition by (Z)-5-[(4-benzyloxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SO42-
-
ammonium and lithium salt is somewhat more effective than sodium and potassium salt
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
the enzyme generates non-hyperbolic kinetics, mimicking a negative cooperative behavior, due to the simultaneous action of two enzyme forms acting on the same substrate. The apparent cooperative behavior of AR acting on glucose and other hexoses and pentoses, but not on tethroses, glyceraldehyde, 4-hydroxynonenal and 4-nitrobenzaldehyde, is generated by a partial nonclassical competitive inhibition exerted by the aldose hemiacetal on the reduction of the free aldehyde, Michaelis-Menten kinetic modelling with substrate L-idose, nonclassical competitive model, detailed overview
-
additional information
additional information
-
the enzyme generates non-hyperbolic kinetics, mimicking a negative cooperative behavior, due to the simultaneous action of two enzyme forms acting on the same substrate. The apparent cooperative behavior of AR acting on glucose and other hexoses and pentoses, but not on tethroses, glyceraldehyde, 4-hydroxynonenal and 4-nitrobenzaldehyde, is generated by a partial nonclassical competitive inhibition exerted by the aldose hemiacetal on the reduction of the free aldehyde, Michaelis-Menten kinetic modelling with substrate L-idose, nonclassical competitive model, detailed overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
(5-biphenyl-4-ylmethyl-2,4-dioxothiazolidin-3-yl)acetic acid
Bos taurus
-
IC50: 0.0017 mM
0.00026
(5-biphenyl-4-ylmethylene-2,4-dioxothiazolidin-3-yl)-acetic acid
Bos taurus
-
IC50: 0.00026 mM
0.00017
(5-naphthalen-1-ylmethylene-2,4-dioxothiazolidin-3-yl)acetic acid
Bos taurus
-
IC50: 0.00017 mM
0.0123
(Z)-5-[(3-hydroxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
Bos taurus
-
pH 6.8, 37°C
0.0233
(Z)-5-[(3-methoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
Bos taurus
-
pH 6.8, 37°C
0.003
(Z)-5-[(4-hydroxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
Bos taurus
-
pH 6.8, 37°C
0.0174
(Z)-5-[(4-methoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
Bos taurus
-
pH 6.8, 37°C
0.0083
(Z)-5-[(4-phenoxyphenyl)methylidene]-3-(3,3,3-trifluoro-2-oxopropyl)-2,4-thiazolidinedione
Bos taurus
-
pH 6.8, 37°C
0.0253
1,5-bis(4-hydroxy-3,5-dimethoxyphenyl)-1,4-pentadiene-3-one
Bos taurus
-
IC50: 0.0253 mM
0.0208
2,5-bis(3-bromo-4-hydroxy-5-methoxybenzylidene)cyclopentanone
Bos taurus
-
IC50: 0.0208 mM
0.0234
2,5-bis(4-hydroxy-3,5-dimethoxybenzylidene)cyclopentanone
Bos taurus
-
IC50: 0.0234 mM
0.021
2,6-bis(3-bromo-4-hydroxy-5-methoxybenzylidene)cyclohexanone
Bos taurus
-
IC50: 0.021 mM
0.0208
3,5-bis(3-bromo-4-hydroxy-5-methoxybenzylidene)-4-piperidone
Bos taurus
-
IC50: 0.0208 mM
0.0042
4-[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]-2-butenoic acid
Bos taurus
-
IC50: 0.0042 mM
0.0137
bisdemethoxycurcumin
Bos taurus
-
i.e. 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0137 mM
0.0068
curcumin
Bos taurus
-
i.e. 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0068 mM
0.0159
demethoxycurcumin
Bos taurus
-
i.e. 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, extracted from Curcuma longa roots, IC50: 0.0159 mM
0.0314
thienocinnolinone alkanoic acid derivatives
Bos taurus
-
i.e. 8-halogen-4,4a-5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acid derivatives, synthesis and inhibitory potency, IC50 as low as 0.0314 mM, the length of the N2 alkanoic chain strongly influences the inhibitory activity, overview
-
0.001
[2,4-dioxo-5-(3-phenoxybenzyl)thiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.0010 mM
0.0028
[2,4-dioxo-5-(4-phenoxybenzyl)thiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.0028 mM
0.00082
[2,4-dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.00082 mM
0.039
[5-(3-aminobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid methyl ester
Bos taurus
-
IC50: 0.039 mM
0.00066
[5-(3-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.00066 mM
0.003
[5-(3-methoxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.0030 mM
0.0211
[5-(3-methoxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
Bos taurus
-
IC50: 0.0211 mM
0.00049
[5-(3-nitrobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid
Bos taurus
-
IC50: 0.00049 mM
0.00028
[5-(4-benzyloxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.00028 mM
0.0021
[5-(4-hydroxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.0021 mM
0.00015
[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.00015 mM
0.0062
[5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid methyl ester
Bos taurus
-
IC50: 0.0062 mM
0.0011
[5-(4-methoxybenzyl)-2,4-dioxothiazolidin-3-yl]acetic acid
Bos taurus
-
IC50: 0.0011 mM
0.0012
[5-(4-nitrobenzylidene)-2,4-dioxothiazolidin-3-yl]-acetic acid
Bos taurus
-
IC50: 0.0012 mM
additional information
additional information
Bos taurus
inhibition kinetics and thermodynamics, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1.2
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
aldehyde reductase exerts a detoxifying action and at the same time triggers a cell signaling cascade related to the antioxidant defense. The reduction of glucose catalyzed by aldose reductase, which is the first and rate-limiting step of the polyol pathway, is considered as one of the main deleterious events leading to the onset of diabetic complications. In fact, the accumulation of sorbitol and the concomitant reduction in the antioxidant's capability are significant factors leading to cell damage
metabolism
the enzyme is the first rate-determining enzyme in the polyol pathway and catalyzes the reduction of glucose to sorbitol in the presence of NADPH as a cofactor. Sorbitol is in turn converted into fructose with accompanied reduction of NAD+ by sorbitol dehydrogenase
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ALDR_BOVIN
315
0
35919
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
monomer
-
1 * 30000, isozyme AR I, SDS-PAGE, monomer is in equilibrium with a less effective dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
thermal aggregation and precipitation is prevented by specific, thermal stress induced complexing of alpha-crystallin, stable at least for 2 h at 55°C and for hours at room temperature, complexing can be hindered by Tris
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
alpha-crystallin stabilizes the enzyme with higher efficiency at 37°C compared to 25°C
-
dithiothreitol, 2 mM stabilizes, other sulfhydryl compounds such as beta-mercaptoethanol, glutathione and cysteine are less effective
-
extremely labile to freezing and thawing unless Carbowax 100 is included, 10 mg/ml
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from lens by anion exchange and Matrex Orange A affinity chromatography
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
development of reductase inhibitors as drugs counteracting the onset of diabetic complications
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sheaff, C.M.; Doughty, C.C.
Physical and kinetic properties of homogenous bovine lens aldose reductase
J. Biol. Chem.
251
2696-2702
1976
Bos taurus
Cromlish, J.A.; Flynn, T.G.
Purification and characterization of two aldose reductase isoenzymes from rabbit muscle
J. Biol. Chem.
258
3416-3424
1983
Bos taurus, Oryctolagus cuniculus, Rattus norvegicus, Sus scrofa
Dons, R.F.; Doughty, C.C.
Isolation and characterization of aldose reductase from calf brain
Biochim. Biophys. Acta
452
1-12
1976
Bos taurus
Hayman, S.; Kinoshita, J.H.
Isolation and properties of lens aldose reductase
J. Biol. Chem.
240
877-882
1965
Bos taurus
Attwood, M.A.; Doughty, C.C.
Purification and properties of calf liver aldose reductase
Biochim. Biophys. Acta
370
358-368
1974
Bos taurus
Halder, A.B.; Crabbe, M.J.C.
Bovine lens aldehyde reductase (aldose reductase)
Biochem. J.
219
33-39
1984
Bos taurus
Ryle, C.M.; Dowling, T.G.; Tipton, K.F.
Purification and properties of low-KM aldehyde reductase from ox brain
Biochim. Biophys. Acta
791
155-163
1984
Bos taurus
Ryle, C.M.; Tipton, K.F.
Kinetic studies with low-KM aldehyde reductase from ox brain
Biochem. J.
227
621-627
1985
Bos taurus
Marini, I.; Bucchioni, L.; Voltarelli, M.; Del Corso, A.; Mura, U.
Alpha-crystallin-like molecular chaperone against the thermal denaturation of lens aldose reductase: the effect of divalent metal ions
Biochem. Biophys. Res. Commun.
212
413-420
1995
Bos taurus
Cecconi, I.; Scaloni, A.; Rastelli, G.; Moroni, M.; Vilardo, P.G.; Costantino, L.; Cappiello, M.; Garland, D.; Carper, D.; Petrash, J.M.; Del Corso, A.; Mura, U.
Oxidative modification of aldose reductase induced by copper ion. Definition of the metal-protein interaction mechanism
J. Biol. Chem.
277
42017-42027
2002
Bos taurus, Homo sapiens, Rattus norvegicus
Dal Monte, M.; Del Corso, A.; Moschini, R.; Cappiello, M.; Amodeo, P.; Mura, U.
Zofenoprilat-glutathione mixed disulfide as a specific S-thiolating agent of bovine lens aldose reductase
Antioxid. Redox Signal.
7
841-848
2005
Bos taurus
Moschini, R.; Marini, I.; Malerba, M.; Cappiello, M.; Del Corso, A.; Mura, U.
Chaperone-like activity of alpha-crystallin toward aldose reductase oxidatively stressed by copper ion
Arch. Biochem. Biophys.
453
13-17
2006
Bos taurus
Du, Z.Y.; Bao, Y.D.; Liu, Z.; Qiao, W.; Ma, L.; Huang, Z.S.; Gu, L.Q.; Chan, A.S.
Curcumin analogs as potent aldose reductase inhibitors
Arch. Pharm.
339
123-128
2006
Bos taurus
Maccari, R.; Ottana, R.; Curinga, C.; Vigorita, M.G.; Rakowitz, D.; Steindl, T.; Langer, T.
Structure-activity relationships and molecular modelling of 5-arylidene-2,4-thiazolidinediones active as aldose reductase inhibitors
Bioorg. Med. Chem.
13
2809-2823
2005
Bos taurus
Rakowitz, D.; Maccari, R.; Ottana, R.; Vigorita, M.G.
In vitro aldose reductase inhibitory activity of 5-benzyl-2,4-thiazolidinediones
Bioorg. Med. Chem.
14
567-574
2006
Bos taurus
Pau, A.; Asproni, B.; Murineddu, G.; Boatto, G.; Grella, G.E.; Rakowitz, D.; Costantino, L.; Pinna, G.A.
Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors
Med. Chem.
2
39-45
2006
Bos taurus
Maccari, R.; Ciurleo, R.; Giglio, M.; Cappiello, M.; Moschini, R.; Corso, A.D.; Mura, U.; Ottana, R.
Identification of new non-carboxylic acid containing inhibitors of aldose reductase
Bioorg. Med. Chem.
18
4049-4055
2010
Bos taurus
Balestri, F.; Cappiello, M.; Moschini, R.; Rotondo, R.; Buggiani, I.; Pelosi, P.; Mura, U.; Del-Corso, A.
L-Idose: an attractive substrate alternative to D-glucose for measuring aldose reductase activity
Biochem. Biophys. Res. Commun.
456
891-895
2015
Homo sapiens (P15121), Homo sapiens, Bos taurus (P16116), Bos taurus
Balestri, F.; Cappiello, M.; Moschini, R.; Rotondo, R.; Abate, M.; Del-Corso, A.; Mura, U.
Modulation of aldose reductase activity by aldose hemiacetals
Biochim. Biophys. Acta
1850
2329-2339
2015
Homo sapiens (P15121), Homo sapiens, Bos taurus (P16116), Bos taurus
Iqbal, Z.; Hameed, S.; Ali, S.; Tehseen, Y.; Shahid, M.; Iqbal, J.
Synthesis, characterization, hypoglycemic and aldose reductase inhibition activity of arylsulfonylspiro[fluorene-9,5-imidazolidine]-2,4-diones
Eur. J. Med. Chem.
98
127-138
2015
Bos taurus (P16116)
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