BRENDA - Enzyme Database

Metabolism of (13)C5-hydroxyproline in mouse models of primary hyperoxaluria and its inhibition by RNAi therapeutics targeting liver glycolate oxidase and hydroxyproline dehydrogenase

Li, X.; Knight, J.; Fargue, S.; Buchalski, B.; Guan, Z.; Inscho, E.W.; Liebow, A.; Fitzgerald, K.; Querbes, W.; Todd Lowther, W.; Holmes, R.P.; Biochim. Biophys. Acta 1862, 233-239 (2016)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
1.1.3.15
medicine
the ability of such siRNAs to reduce urinary oxalate in the mouse model suggests that this approach is promising for the treatment of primary hyperoxalurias, PH, particularly PH type I, in humans, genes HYPDH and GO appear to be the best targets for reducing the production of glyoxylate and oxalate in PH patients
Mus musculus
Engineering
EC Number
Amino acid exchange
Commentary
Organism
1.1.3.15
additional information
enzyme knockout by specific siRNA targeting the liver enzyme glycolate oxidase in wild-type leads to greatly decreased GO activity, 20fold increased urinary excretion of glycolate, and more than 2fold increased urinary oxalate excretion compared to controls. Treatment of mutant Agxt KO mice, that are deficient in liver alanine:glyoxylate aminotransferase, leads to significantly decreased urinary oxalate excretion, but substantially increased urinary glycolate excretion
Mus musculus
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
1.1.3.15
peroxisome
-
Mus musculus
5777
-
1.5.5.3
mitochondrion
-
Mus musculus
5739
-
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.3.15
glycolate + O2
Mus musculus
-
glyoxylate + H2O2
-
-
?
1.1.3.15
glycolate + O2
Mus musculus C57BL/6J
-
glyoxylate + H2O2
-
-
?
1.5.5.3
trans-4-hydroxy-L-proline + a quinone
Mus musculus
-
(3R,5S)-3-hydroxy-1-pyrroline-5-carboxylate + a quinol
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.1.3.15
Mus musculus
Q9WU19
-
-
1.1.3.15
Mus musculus C57BL/6J
Q9WU19
-
-
1.5.5.3
Mus musculus
-
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.3.15
hepatocyte
-
Mus musculus
-
1.1.3.15
liver
-
Mus musculus
-
1.5.5.3
liver
-
Mus musculus
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.3.15
glycolate + O2
-
741999
Mus musculus
glyoxylate + H2O2
-
-
-
?
1.1.3.15
glycolate + O2
-
741999
Mus musculus C57BL/6J
glyoxylate + H2O2
-
-
-
?
1.5.5.3
trans-4-hydroxy-L-proline + a quinone
-
741999
Mus musculus
(3R,5S)-3-hydroxy-1-pyrroline-5-carboxylate + a quinol
-
-
-
?
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.3.15
7.1
-
assay at
Mus musculus
Application (protein specific)
EC Number
Application
Commentary
Organism
1.1.3.15
medicine
the ability of such siRNAs to reduce urinary oxalate in the mouse model suggests that this approach is promising for the treatment of primary hyperoxalurias, PH, particularly PH type I, in humans, genes HYPDH and GO appear to be the best targets for reducing the production of glyoxylate and oxalate in PH patients
Mus musculus
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
1.1.3.15
additional information
enzyme knockout by specific siRNA targeting the liver enzyme glycolate oxidase in wild-type leads to greatly decreased GO activity, 20fold increased urinary excretion of glycolate, and more than 2fold increased urinary oxalate excretion compared to controls. Treatment of mutant Agxt KO mice, that are deficient in liver alanine:glyoxylate aminotransferase, leads to significantly decreased urinary oxalate excretion, but substantially increased urinary glycolate excretion
Mus musculus
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
1.1.3.15
peroxisome
-
Mus musculus
5777
-
1.5.5.3
mitochondrion
-
Mus musculus
5739
-
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.3.15
glycolate + O2
Mus musculus
-
glyoxylate + H2O2
-
-
?
1.1.3.15
glycolate + O2
Mus musculus C57BL/6J
-
glyoxylate + H2O2
-
-
?
1.5.5.3
trans-4-hydroxy-L-proline + a quinone
Mus musculus
-
(3R,5S)-3-hydroxy-1-pyrroline-5-carboxylate + a quinol
-
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.3.15
hepatocyte
-
Mus musculus
-
1.1.3.15
liver
-
Mus musculus
-
1.5.5.3
liver
-
Mus musculus
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.3.15
glycolate + O2
-
741999
Mus musculus
glyoxylate + H2O2
-
-
-
?
1.1.3.15
glycolate + O2
-
741999
Mus musculus C57BL/6J
glyoxylate + H2O2
-
-
-
?
1.5.5.3
trans-4-hydroxy-L-proline + a quinone
-
741999
Mus musculus
(3R,5S)-3-hydroxy-1-pyrroline-5-carboxylate + a quinol
-
-
-
?
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.3.15
7.1
-
assay at
Mus musculus
General Information
EC Number
General Information
Commentary
Organism
1.1.3.15
malfunction
evaluation of the potential of siRNAs targeting the synthesis of liver glycolate oxidase or hydroxyproline dehydrogenase formulated in lipid nanoparticles, to reduce urinary oxalate excretion in Agxt KO mice. The siRNA targeting glycolate oxidase blocks a downstream step and prevents the synthesis of glyoxylate from glycolate in the liver. The ability of such siRNAs to reduce urinary oxalate in the mouse model suggests that this approach is promising for the treatment of primary hyperoxalurias, PH, particularly PH type I, in humans
Mus musculus
1.5.5.3
malfunction
enzyme knockdown alters glycolate and oxalate levels
Mus musculus
General Information (protein specific)
EC Number
General Information
Commentary
Organism
1.1.3.15
malfunction
evaluation of the potential of siRNAs targeting the synthesis of liver glycolate oxidase or hydroxyproline dehydrogenase formulated in lipid nanoparticles, to reduce urinary oxalate excretion in Agxt KO mice. The siRNA targeting glycolate oxidase blocks a downstream step and prevents the synthesis of glyoxylate from glycolate in the liver. The ability of such siRNAs to reduce urinary oxalate in the mouse model suggests that this approach is promising for the treatment of primary hyperoxalurias, PH, particularly PH type I, in humans
Mus musculus
1.5.5.3
malfunction
enzyme knockdown alters glycolate and oxalate levels
Mus musculus