Information on EC 4.1.3.16 - 4-Hydroxy-2-oxoglutarate aldolase

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The expected taxonomic range for this enzyme is: Mammalia

EC NUMBER
COMMENTARY
4.1.3.16
-
RECOMMENDED NAME
GeneOntology No.
4-Hydroxy-2-oxoglutarate aldolase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
condensation
-
-
-
-
elimination
-
-
of an oxo-acid, C-C bond cleavage
-
PATHWAY
KEGG Link
MetaCyc Link
4-hydroxyproline degradation
-
Arginine and proline metabolism
-
Glyoxylate and dicarboxylate metabolism
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
4-hydroxy-2-oxoglutarate glyoxylate-lyase (pyruvate-forming)
The enzymes from rat liver and bovine liver act on both enantiomers of 4-hydroxy-2-oxoglutarate. cf. EC 4.1.3.42, L-4-hydroxy-2-oxoglutarate aldolase.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2-keto-4-hydroxybutyrate aldolase
-
-
-
-
2-keto-4-hydroxyglutarate aldolase
-
-
-
-
2-keto-4-hydroxyglutaric aldolase
-
-
-
-
2-oxo-4-hydroxyglutarate aldolase
-
-
-
-
2-oxo-4-hydroxyglutaric aldolase
-
-
-
-
4-hydroxy-2-ketoglutarate aldolase
-
-
-
-
4-hydroxy-2-ketoglutaric aldolase
-
-
-
-
4-hydroxy-2-oxoglutarate aldolase
Q86XE5
-
aldolase, 4-hydroxy-2-oxoglutarate
-
-
-
-
DHDPSL
Q86XE5
-
dihydrodipicolinate synthase-like enzyme
Q86XE5
-
DL-4-Hydroxy-2-ketoglutarate aldolase
-
-
-
-
EC 4.1.2.31
-
-
formerly
-
hOGA
Q86XE5
-
hydroxyketoglutarate aldolase
-
-
-
-
Hydroxyketoglutaric aldolase
-
-
-
-
KHG-aldolase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9030-81-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
; bovine
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
mutations are responsible for primary hyperoxaluria type III
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-Keto-4-hydroxybutyrate
Pyruvate + formaldehyde
show the reaction diagram
-
D-isomer favoured
-
-
2-Keto-4-hydroxybutyrate
?
show the reaction diagram
-
metabolism of L-homoserine
-
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
r
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
both stereoisomers
-
-
4-Hydroxy-2-oxoglutarate
Pyruvate + glyoxylate
show the reaction diagram
-
both stereoisomers
-
-
4-hydroxy-2-oxoglutarate
?
show the reaction diagram
-
-
-
-
-
4-hydroxy-2-oxoglutarate
?
show the reaction diagram
-
catabolism of hydroxyproline, condensation physiologically less important
-
-
-
D-4-hydroxy-2-oxoglutarate
pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
r
Glyoxylate + pyruvate
4-Hydroxy-2-ketoglutarate
show the reaction diagram
-
specific, codensation favoured, Keq: 0.73 mM
-
-
Glyoxylate + pyruvate
4-Hydroxy-2-ketoglutarate
show the reaction diagram
-
3-substituted analogs
-
-
-
Glyoxylate + pyruvate
4-Hydroxy-2-ketoglutarate
show the reaction diagram
-
higher specificity for pyruvate than for glyoxylate
-
-
-
Oxaloacetate
CO2 + pyruvate
show the reaction diagram
-
-
-
-
-
Oxaloacetate
CO2 + pyruvate
show the reaction diagram
-
-
-
-
Oxaloacetate
CO2 + pyruvate
show the reaction diagram
-
-
-
-
-
Oxaloacetate
CO2 + pyruvate
show the reaction diagram
-
beta-decarboxylation, about 50% as effective as aldolase
-
-
Pyruvate + formaldehyde
2-Keto-4-hydroxybutyrate
show the reaction diagram
-
Keq: 4.1 mM
-
-
pyruvate + glyoxylate
D-4-hydroxy-2-oxoglutarate
show the reaction diagram
-
-
-
-
r
L-4-hydroxy-2-oxoglutarate
pyruvate + glyoxylate
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
-
-
-
-
additional information
?
-
-
mechanism
-
-
-
additional information
?
-
-
specific for glyoxylate and pyruvate
-
-
-
additional information
?
-
-
functional role of SH-groups, conformational changes during catalysis
-
-
-
additional information
?
-
-
Keq: 11 mM
-
-
-
additional information
?
-
-
equilibrium favours condensation, Keq: 0.73 1/mM
-
-
-
additional information
?
-
-
2-keto-4-hydroxy-4-methylglutarate, 2-keto-3-deoxy-6-phosphoclucanate cleaved at slow rate
-
-
-
additional information
?
-
-
acts on both stereoisomers
-
-
-
additional information
?
-
-
acts on both stereoisomers
-
-
-
additional information
?
-
-
2-keto-3-deoxyglucarate and 2-keto-4,5-dihydroxyvalerate cleaved at slow rate
-
-
-
additional information
?
-
-
2-keto-3-deoxyglucarate and 2-keto-4,5-dihydroxyvalerate cleaved at slow rate
-
-
-
additional information
?
-
-
enzyme performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases
-
-
-
additional information
?
-
-
enzyme shows no stereospecificity in catalyzing the aldol cleavage of the two optical isomers of 2-keto-4-hydroxyglutarate. Enzyme also catalyzes the beta-decarboxylation of oxalacetate, its decarboxylase/aldolae activity ratio is lower than that seen with the pure enzyme from either bovine liver or Escherichia coli
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2-Keto-4-hydroxybutyrate
?
show the reaction diagram
-
metabolism of L-homoserine
-
-
-
4-hydroxy-2-oxoglutarate
?
show the reaction diagram
-
-
-
-
-
4-hydroxy-2-oxoglutarate
?
show the reaction diagram
-
catabolism of hydroxyproline, condensation physiologically less important
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
no requirement
additional information
-
no requirement
additional information
-
no requirement
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-Ketobutyrate
-
competitive, Ki for 2-keto-4-hydroxybutyrate cleavage: 53 mM, Ki for 2-keto-4-hydroxyglutarate cleavage: 52 mM
2-Ketoglutarate
-
competitive, Ki for 2-keto-4-hydroxybutyrate cleavage: 18 mM, Ki for 2-keto-4-hydroxyglutarate cleavage: 18 mM
2-Ketoglutarate
-
; 12% inhibition at 20 mM
4-hydroxy-2-oxoglutarate
-
substrate inhibition, Ki: 35 mM
5,5'-dithiobis(2-nitrobenzoate)
-
glyoxylate and pyruvate protect
acetaldehyde
-
-
beta-Hydroxypyruvate
-
-
Bromopyruvate
-
Ki: 0.018 mM
chloride
-
41% inhibition at 40 mM
citrate
-
-
CN-
-
irreversible, in presence of aldehydes, reversible in abscence of aldehydes, 2-keto-4-hydroxyglutarate cleavage, Ki: 0.57 mM
Cu2+
-
93% inhibition at 2 mM
cysteine
-
65% inhibition at 10 mM
Dithiodipyridine
-
kidney enzyme
glycolaldehyde
-
competitive, Ki for 2-keto-4-hydroxybutyrate cleavage: 2.7 mM, Ki for 2-keto-4-hydroxyglutarate cleavage: 2.4 mM
Glyoxal
-
36% inhibition at 20 mM
glyoxylate
-
bovine enzyme inhibited at lower concentrations than E. coli enzyme
glyoxylate
-
Ki: 1.5 mM
Halides
-
-
-
Hg2+
-
complete inhibition at 2 mM
Hg2+
-
100% inhibition at 1 microM; kidney enzyme, complete inhibition at 1 mM
Hydroxypyruvate
-
91% inhibition at 20 mM
iodoacetate
-
10% inhibition at 10 mM
Mercaptopyruvate
-
-
N-ethylmaleimide
-
64% inhibition at 10 mM
NaBH4
-
azomethine formation with substrates and substrate analogues
NaBH4
-
incubation of the enzyme with either pyruvate or glyoxylate in the presence of NaBH4 causes extensive loss of aldolase activity concomitant with stable binding of about 1.0-1.5 mol of substrate/mol of enzyme
NaBr
-
18% inhibition at 50 mM, only condensation
NaF
-
15% inhibition at 50 mM, only condensation
oxaloacetate
-
competitive, Ki: 0.22 mM
p-chloromercuribenzoate
-
complete inhibition at 10 mM
p-chloromercuribenzoate
-
-
p-mercuribenzoate
-
kidney enzyme
pyruvate
-
analogs
Sulfhydryl-reacting reagents
-
-
-
Mn2+
-
65% inhibition at 10 mM; kidney enzyme, 65% inhibition at 10 mM
additional information
-
-
-
additional information
-
double inhibitor studies
-
additional information
-
; not inhibitory: mercaptoethanol, EDTA, 1,10-phenanthroline, alpha,alpha'-dipyridyl, or 8-hydroxyquinoline up to 10 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
50 mM, enhances activity 2fold; activates kidney enzyme
KCl
-
activates
additional information
-
carboxylic acids activate
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.11
-
(D)-4-hydroxy-alpha-ketoglutarate
-
-
0.14
-
(D)-4-hydroxy-alpha-ketoglutarate
-
-
0.22
-
(L)-4-hydroxy-alpha-ketoglutarate
-
-
71
-
(L)-4-hydroxy-alpha-ketoglutarate
-
-
3.1
-
2-Keto-4-hydroxybutyrate
-
-
7.7
-
3-(4-hydroxyphenyl)pyruvate
-
-
7.4
-
3-(4-imidazole)pyruvate
-
-
0.008
-
4-hydroxy-2-oxoglutarate
-
mutant Y140F, pH 8.5, 37C
0.011
-
4-hydroxy-2-oxoglutarate
-
wild-type, pH 8.5, 37C
0.016
-
4-hydroxy-2-oxoglutarate
-
mutant N78T, pH 8.5, 37C
0.044
-
4-hydroxy-2-oxoglutarate
-
mutant S198A, pH 8.5, 37C
0.058
-
4-hydroxy-2-oxoglutarate
-
mutant S77T, pH 8.5, 37C
0.066
-
4-hydroxy-2-oxoglutarate
-
mutant N78A, pH 8.5, 37C
0.077
-
4-hydroxy-2-oxoglutarate
-
mutant S198T, pH 8.5, 37C
0.082
-
4-hydroxy-2-oxoglutarate
-
mutant S77V, pH 8.5, 37C
0.084
-
4-hydroxy-2-oxoglutarate
-
mutant S77A, pH 8.5, 37C
0.281
-
4-hydroxy-2-oxoglutarate
-
mutant N78Q, pH 8.5, 37C
0.1
-
4-hydroxy-alpha-ketoglutarate
-
-
1.33
-
4-hydroxy-alpha-ketoglutarate
-
-
10
-
acetaldehyde
-
-
0.031
-
D-4-hydroxy-2-oxoglutarate
-
pH 8.3, 37C
0.43
-
glyoxylate
-
-
30
-
oxaloacetate
-
condensation with glyoxylate
5.1
-
Pyruvaldehyde
-
-
10
-
pyruvate
-
-
25
-
pyruvate
-
-
2.8
-
Pyruvic acid ethyl ester
-
-
3.2
-
pyruvic acid methyl ester
-
-
0.024
-
L-4-hydroxy-2-oxoglutarate
-
pH 8.3, 37C
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.8
-
4-hydroxy-2-oxoglutarate
-
mutant S77T, pH 8.5, 37C
1.2
-
4-hydroxy-2-oxoglutarate
-
mutant S77V, pH 8.5, 37C
2.4
-
4-hydroxy-2-oxoglutarate
-
mutant S198A, pH 8.5, 37C
2.5
-
4-hydroxy-2-oxoglutarate
-
mutant S77A, pH 8.5, 37C
4
-
4-hydroxy-2-oxoglutarate
-
mutant N78T, pH 8.5, 37C
5.2
-
4-hydroxy-2-oxoglutarate
-
mutant Y140F, pH 8.5, 37C
6.1
-
4-hydroxy-2-oxoglutarate
-
wild-type, pH 8.5, 37C
6.2
-
4-hydroxy-2-oxoglutarate
-
mutant N78Q, pH 8.5, 37C
7.6
-
4-hydroxy-2-oxoglutarate
-
mutant N78A, pH 8.5, 37C
7.8
-
4-hydroxy-2-oxoglutarate
-
mutant S198T, pH 8.5, 37C
13.5
-
DL-2-keto-4-hydroxyglutarate
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
14
-
4-hydroxy-2-oxoglutarate
-
mutant S77T, pH 8.5, 37C
4523
15
-
4-hydroxy-2-oxoglutarate
-
mutant S77V, pH 8.5, 37C
4523
22
-
4-hydroxy-2-oxoglutarate
-
mutant N78Q, pH 8.5, 37C
4523
30
-
4-hydroxy-2-oxoglutarate
-
mutant S77A, pH 8.5, 37C
4523
55
-
4-hydroxy-2-oxoglutarate
-
mutant S198A, pH 8.5, 37C
4523
101
-
4-hydroxy-2-oxoglutarate
-
mutant S198T, pH 8.5, 37C
4523
115
-
4-hydroxy-2-oxoglutarate
-
mutant N78A, pH 8.5, 37C
4523
250
-
4-hydroxy-2-oxoglutarate
-
mutant N78T, pH 8.5, 37C
4523
555
-
4-hydroxy-2-oxoglutarate
-
wild-type, pH 8.5, 37C
4523
650
-
4-hydroxy-2-oxoglutarate
-
mutant Y140F, pH 8.5, 37C
4523
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
35
-
4-hydroxy-2-oxoglutarate
-
substrate inhibition
0.018
-
Bromopyruvate
-
-
0.22
-
oxaloacetate
-
competitive
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.53
-
-
2-keto-4-hydroxybutyrate
1.8
-
-
2-keto-4-hydroxyglutarate
9.23
-
-
kidney enzyme; pH 8.4, 37C
9.7
-
-
-
15.8
-
-
pH 8.5, 37C
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
8
-
condensation, elimination
8.1
-
-
2-keto-4-hydroxybutyrate cleavage
8.8
-
-
2-keto-4-hydroxyglutarate cleavage
8.8
-
-
; 2-keto-4-hydroxyglutarate cleavage
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
9.5
-
2-keto-4-hydroxybutyrate cleavage
6.3
-
-
50% of maximum activity
7
9
-
2-keto-4-hydroxyglutarate cleavage
9.6
-
-
60% of maximum activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
enzyme assay at
37
-
-
enzyme assay at
37
-
-
enzyme assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
poor activity
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
11% of total activity
Manually annotated by BRENDA team
-
89% of total activity
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
72000
-
-
gel filtration
97200
-
-
sedimentation equilibrium centrifugation
120000
-
-
gel filtration
120000
-
-
gel filtration
131500
-
-
gel filtration
138000
-
-
sucrose density gradient centrifugation
140000
-
-
gel filtration
144000
-
-
gel filtration, sucrose density gradient centrifugation, kidney enzyme
144500
-
-
sedimentation equilibrium centrifugation
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
and tetramer, in equilibrium, 2 * 35249, calculated
tetramer
-
4 * 35700, SDS-PAGE; 4 * 36000, SDS-PAGE, amino acid composition, kidney enzyme
tetramer
-
4 * 35249, calculated
tetramer
-
and dimer, in equilibrium, 4 * 35249, calculated
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
to 1.97 A resolution, crystal structure of enzyme bound to pyruvate. Modeling of the 4-hydroxy-2-oxoglutarate-Schiff base intermediate and kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
59
-
-
constant decay of 0.011 1/min, slow inactivation
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
irreversibly inactivated by aminonitrile formation from cyanide and enzyme-substrate complex
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, Tris-HCl buffer, pH 7.4, 40% saturated with ammonium sulfate, 6 months, kidney enzyme
-
4C, in either 50 mM Tris-HCl or potassium phosphate, pH 7.4, plus 5 mM 2-mercaptoethanol, 0.02% sodium azide, 40% saturated with ammonium sulfate, 100% of initial activity for at least 6 months
-
4C, in either 50 mM Tris-HCl or potassium phosphate, pH 7.4, plus 5 mM 2-mercaptoethanol, 0.02% sodium azide, no substantial loss of enzymatic activity for up to 1 month
-
5C, Tris-HCl buffer, pH 7.4, two weeks, sometimes several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
; kidney enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C257G
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
DeltaE315
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
G287V
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
K196A
-
complete loss of activity
N78A
-
20% of wild-type activity
N78Q
-
4% of wild-type activity
N78T
-
45% of wild-type activity
P190L
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R255X
-
a truncation of 71 residues from the C-terminus associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R303C
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R70P
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R97C
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
S198A
-
9% of wild-type activity
S198T
-
18% of wild-type activity
S77A
-
5% of wild-type activity
S77T
-
2% of wild-type activity
S77V
-
2% of wild-type activity
T280I
-
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Y140F
-
122% of wild-type activity
Y168F
-
complete loss of activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3, PH3. Analysis of nine PH3 human variants reveals that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of 4-hydroxy-2-oxoglutarate takes place in the urine, sera and liver samples from PH3 patients. One hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of glyoxylate reductase by 4-hydroxy-2-oxoglutarate, resulting in a phenotype similar to Primary Hyperoxaluria type 2
synthesis
-
use as synthetic tool for C-C bond formation considered