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Literature summary for 6.3.4.5 extracted from

  • Satoh, M.; Iwahori, T.; Sugawara, N.; Yamazaki, M.
    Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid A and inactivates their biological activities (2006), J. Endotoxin Res., 12, 21-38.
    View publication on PubMed

Application

Application Comment Organism
medicine argininosuccinate synthetase is inhibited by endotoxin, implying that bacterial products might potentially regulate the arginine metabolism in the host and perturb NO synthesis Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
diphosphoryl lipid A (DPL) DPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.039 mg/ml Mus musculus
monophosphoryl lipid A (MPL) MPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.270 mg/ml Mus musculus
R-lipopolysaccharide (LPS) rough-type LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.230 mg/ml Mus musculus
S-lipopolysaccharide (LPS) smooth-type-LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.024 mg/ml Mus musculus
sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(9-phenyl-nonanoyl)-D-glucopyranose 4-sulfate synthesized lipid A analog, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.0065 mg/ml Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Mus musculus

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
45000
-
SDS-PAGE Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
analysis by native gel electrophoresis shows that argininosuccinate synthetase can bind bacterial lipopolysaccharide and lipid A Mus musculus
argininosuccinate synthetase is purified from mouse liver. Livers are excised from 20 male mice (C3H/He strain, age 7-8 weeks) and homogenized in 100 mM Tris-HCl (pH 7.5) containing 1 mM citrulline and 1 mM aspartic acid. Homogenate is centrifuged. After salting-out with (NH4)2SO4. The sample is subjected to anion-exchange chromatography on DE-52. Concentrated samples are loaded on a column of Sephacryl S-300 HR. The collected first peak fractions are dialyzed and subjected to anion-exchange chromatography on UNO S-1 Mus musculus

Reaction

Reaction Comment Organism Reaction ID
ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nomega-L-arginino)succinate it is found that argininosuccinate synthetase is the major lipid A-interacting protein in liver. Argininosuccinate synthetase also inhibits the biological activities of natural lipid A and rough-type lipopolysaccharide and but not smooth-type lipopolysaccharide. Argininosuccinate synthetase enzyme activity is inhibited by lipid A and rough-type lipopolysaccharide and smooth-type lipopolysaccharide. Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Mus musculus
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
0.14
-
purification step: liver homogenate supernatant Mus musculus
0.27
-
purification step: 45-55% saturated ammonium sulfate precipitate Mus musculus
0.99
-
purification step: DE-52 fraction Mus musculus
1.39
-
purification step: S-300 fraction Mus musculus
5.16
-
purification step: UNO S-1 fraction Mus musculus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-citrulline + L-aspartate
-
Mus musculus AMP + diphosphate + L-argininosuccinate
-
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Synonyms

Synonyms Comment Organism
Argininosuccinate synthetase
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
substrate: diphosphoryl lipid A, IC50: 0.039 mg/ml Mus musculus additional information
additional information
-
substrate: monophosphoryl lipid A, IC50: 0.270 mg/ml Mus musculus additional information
additional information
-
substrate: R-lipopolysaccharide, IC50: 0.230 mg/ml Mus musculus additional information
additional information
-
substrate: S-lipopolysaccharide, IC50: 0.024 mg/ml Mus musculus additional information
additional information
-
substrate: sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(p-phenyl-nonanoyl)-D-glucopyranose 4-sulfate (ONO-4007), IC50: 0.0065 mg/ml Mus musculus additional information