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Literature summary for 1.1.1.21 extracted from

  • Kaiserova, K.; Srivastava, S.; Hoetker, J.D.; Awe, S.O.; Tang, X.L.; Cai, J.; Bhatnagar, A.
    Redox activation of aldose reductase in the ischemic heart (2006), J. Biol. Chem., 281, 15110-15120.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
DTT activates the enzyme in healthy heart slightly, but slightly inhibits the ischemic heart enzyme Rattus norvegicus
peroxynitrite peroxynitrite activates by oxidizing cysteine resiudes to sulfenic acid. C298 is the major site of sulfenic acid formation and oxidation of C298 is necessary and sufficient for enzyme activation by peroxynitrite Homo sapiens
sulfate activates the enzyme in ischemic heart Rattus norvegicus

Application

Application Comment Organism
medicine treatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester prevented ischemia-induced aldose reductase activation and myocardial sorbitol accumulation in rat hearts subjected to global ischemia ex vivo or coronary ligation in situ, whereas inhibition of inducible nitric oxide synthase and neuronal nitric oxide synthase have no effect. Activation of aldose reductase in the ischemic heart is abolished by pretreatment with peroxynitrite scavengers hesperetin or 5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron [III] Rattus norvegicus

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli, with His-tag Homo sapiens

Protein Variants

Protein Variants Comment Organism
C298S treatment with peroxynitrite does not significantly affect the catalytic activity of C298S, and enzyme is insensitive to dimedone Homo sapiens
C303S mutant is activated by peroxynitrite, and the peroxynitrite-modified protein is inhibited by dimedone Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
DTT activates the enzyme in healthy heart slightly, but slightly inhibits the ischemic heart enzyme Rattus norvegicus
sorbinil
-
Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics Rattus norvegicus
0.071
-
DL-glyceraldehyde pH 6.0, 25°C, healthy heart Rattus norvegicus
0.0835
-
DL-glyceraldehyde pH 6.0, 25°C, ischemic heart Rattus norvegicus
0.0836
-
DL-glyceraldehyde pH 6.0, 25°C, healthy heart, in presence of DTT Rattus norvegicus
0.0934
-
DL-glyceraldehyde pH 6.0, 25°C, ischemic heart, in presence of DTT Rattus norvegicus
0.0973
-
DL-glyceraldehyde presence of peroxynitrite, pH 7.0, 37°C Homo sapiens
0.124
-
DL-glyceraldehyde pH 7.0, 37°C Homo sapiens
0.1734
-
DL-glyceraldehyde presence of dimedone, pH 7.0, 37°C Homo sapiens
0.4287
-
DL-glyceraldehyde presence of peroxynitrite and dimedone, pH 7.0, 37°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Rattus norvegicus the enzyme shows increased activity and is redox activated in ischemic heart ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Rattus norvegicus
-
-
-
Rattus norvegicus
-
male sprague-dawley rats
-

Purification (Commentary)

Purification (Comment) Organism
native enzyme partially from left ventricular tissue, by ultracentrifugation and gel filtration Rattus norvegicus

Source Tissue

Source Tissue Comment Organism Textmining
heart healthy and ischemic, left ventricular tissue Rattus norvegicus
-
heart ischemic heart Rattus norvegicus
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
Rattus norvegicus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
DL-glyceraldehyde + NADPH
-
Homo sapiens glycerol + NAD(P)+
-
?
DL-glyceraldehyde + NADPH + H+
-
Rattus norvegicus glycerol + NADP+
-
?
additional information the enzyme shows increased activity and is redox activated in ischemic heart Rattus norvegicus ?
-
?

Synonyms

Synonyms Comment Organism
aldose reductase
-
Rattus norvegicus
AR
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6
-
assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Rattus norvegicus