Information on EC 1.2.1.31 - L-aminoadipate-semialdehyde dehydrogenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.2.1.31
-
RECOMMENDED NAME
GeneOntology No.
L-aminoadipate-semialdehyde dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(S)-2-amino-6-oxohexanoate + NAD(P)+ + H2O = L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
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-
-
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reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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L-lysine degradation XI (mammalian)
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Lysine biosynthesis
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Lysine degradation
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lysine metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
L-2-aminoadipate-6-semialdehyde:NAD(P)+ 6-oxidoreductase
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CAS REGISTRY NUMBER
COMMENTARY hide
9067-87-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
P2
-
-
Manually annotated by BRENDA team
strain AIU Z-35-1
-
-
Manually annotated by BRENDA team
Rhodococcus sp. AIU Z-35-1
strain AIU Z-35-1
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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alpha-AASA dehydrogenase deficiency results in the accumulation of pathognomonic alpha-aminoadipic semialdehyde (in cerebrospinal fluid, plasma and urine) and pipecolic acid (cerebrospinal fluid and plasma) in affected patients
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
show the reaction diagram
-
-
-
?
alpha-aminoadipic semialdehyde + NAD+ + H2O
alpha-aminoadipic acid + NADH + H+
show the reaction diagram
DELTA1-piperidine 6-carboxylate + NAD+ + H2O
L-2-aminoadipate + NADH
show the reaction diagram
L-2-aminoadipate + NADPH
L-2-aminoadipate 6-semialdehyde + NADP+ + H2O
show the reaction diagram
L-2-aminoadipate + NADPH + H+
L-2-aminoadipate 6-semialdehyde + NADP+ + H2O
show the reaction diagram
L-2-aminoadipate 6-semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
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-
-
-
L-2-aminoadipate 6-semialdehyde + NAD+ + H2O
L-2-aminoadipate + NADH
show the reaction diagram
L-2-aminoadipate-semialdehyde + NAD+
L-2-aminoadipate + NADH
show the reaction diagram
L-alpha-aminoadipate + NAD(P)H
L-alpha-aminoadipate-semialdehyde + NAD(P)+ + H2O
show the reaction diagram
L-alpha-aminoadipate-semialdehyde + NAD(P)+ + H2O
L-alpha-aminoadipate + NAD(P)H + H+
show the reaction diagram
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-
-
-
?
Nalpha-benzyloxycarbonyl-L-aminoadipate-delta-semialdehyde + NAD+ + H2O
Nalpha-benzyloxycarbonyl-L-aminoadipate + NADH + H+
show the reaction diagram
S-carboxymethyl-L-cysteine + NADPH
?
show the reaction diagram
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5% of the activity with L-2-aminoadipate
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-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-2-aminoadipate + NADPH + H+
L-2-aminoadipate 6-semialdehyde + NADP+ + H2O
show the reaction diagram
L-2-aminoadipate 6-semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
Q4L235
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-
-
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L-2-aminoadipate-semialdehyde + NAD+
L-2-aminoadipate + NADH
show the reaction diagram
L-alpha-aminoadipate + NAD(P)H
L-alpha-aminoadipate-semialdehyde + NAD(P)+ + H2O
show the reaction diagram
additional information
?
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the enzyme catalyzes both the activation of alpha-aminoadipic acid and its reduction to semialdehyde
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
-
-
pyrroloquinoline quinone
additional information
-
a variety of NAD+ analogues serve as electron acceptor: deamino-NAD+, NADP+, thionicotinamide-NAD+ and 3-acetylpyridine-NAD+
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
stimulates
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetaldehyde
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alpha-aminoadipate
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Butyraldehyde
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Carbonyl reagents
delta-hydroxylysine
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competitive with respect to alpha-aminoadipate, non-competitive with respect to both ATP and NADPH
Disulfiram
0.01 mM
FeCl3
-
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glutamate
hydroxylamine
imidazole
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20% inhibition at 1 mM
L-aspartate
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competitive inhibitor with respect to alpha-aminoadipate
L-lysine
Nalpha-benzyloxycarbonyl-L-aminoadipate-delta-semialdehyde
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Pb(NO3)2
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S-(beta-aminoethyl)-L-cysteine
Sodium diphosphate
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-
additional information
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dehydrogenase activity is not inhibited by Nalpha-Z-L-lysine and Nalpha-benzyloxycarbonyl-L-aminoadipate at pH 5.0 or 7.0
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
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10 mM, activates
dithiothreitol
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10 mM, activates
L-cysteine
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10 mM, activates
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
2-aminoadipic semialdehyde
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-
0.2 - 0.78
alpha-aminoadipate
0.5 - 1.3
ATP
0.002
DELTA1-piperidine 6-carboxylate
1.4
L-2-aminoadipate
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pH 8, 30C
0.181
L-2-aminoadipate 6-semialdehyde
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-
0.77 - 3.8
MgCl2
0.2 - 0.454
NAD+
0.38
NADH
-
-
0.1 - 0.62
NADPH
0.888 - 1.34
Nalpha-benzyloxycarbonyl-L-aminoadipate-delta-semialdehyde
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
11.2
alpha-aminoadipate semialdehyde
Saccharomyces cerevisiae
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production from holo-lys2
66
L-2-aminoadipate
Penicillium chrysogenum
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pH 8, 30C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.65
delta-hydroxylysine
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4.2
L-aspartate
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-
1.5
L-glutamate
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8.6 - 50
Nalpha-benzyloxycarbonyl-L-aminoadipate-delta-semialdehyde
0.007
S-(beta-aminoethyl)-L-cysteine
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00077
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cytosol fraction
0.0063
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5 mM L-lysine as supplement during growth of the enzyme
0.0072
0.00996
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wild type
0.0102
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lysine auxotropic mutant G16
0.0105
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lysine auxotropic mutant G12
0.0108
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lysine auxotropic mutants G108 and G358
0.0114
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lysine auxotropic mutant G285
0.0138
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10 mM amitrole as supplement during growth of the enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
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8.1
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L-alpha-aminoadipate-semialdehyde reduction
8.2
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L-alpha-aminoadipate-semialdehyde reduction
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9
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pH 5: about 30% of activity maximum, pH 9: about 40% of activity maximum
5 - 8.5
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6 - 9
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pH 6: about 10% of activity maximum, pH 9: about 70% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 50
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-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
colon adenocarcinoma, CX-1; colon adenocarcinoma, GI-112
Manually annotated by BRENDA team
lung carcinoma, GI-117; lung carcinoma, LX-1
Manually annotated by BRENDA team
ovarian carcinoma, GI-102
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
prostatic adenocarcinoma, PC3
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31000
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Lys5 from induced E. coli cells
154900
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analysis of the nucleotide sequence of the 5.1-kb region
155000
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full-length Lys2 from induced E. coli cells
160000
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gel filtration
171000
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gel filtration
180000
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gel filtration
250000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 155000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
side-chain modification
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
activity is significantly decreased in acidic pH regions, yet the difference in activity is maximum at pH 5.0. The dehydrogenase is unstable in alkaline pH regions
693281
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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15 min, 50% loss of activity
additional information
-
enzyme activity at 10C is less than 10% of the maximum activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
addition of 10 mM 2-mercaptoethanol and protease inhibitors e.g.: 5 mM EDTA, 1 mM phenylmethylsulfonyl fluoride to the crude extract improves stability
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freezing-thawing, frozen enzyme loses 10-20% of activity during each freeze-thaw cycle
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low ionic strength: unstable
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lyophilization inactivates
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 0.02 mM potassium phosphate buffer, pH 7.0, 5 mM 2-mercaptoethanol, 3 months
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-20C, 50% v/v glycerol, rapid loss of activity
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0C, 50% loss of activity, 24 h
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial, using column chromatography on DEAE-cellulose, gel filtration, hydrolxylapatite and Reactive Red-120 agarose
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using ammonium sulfate fractionation and column chromatography on CM-Sephadex
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using column chromatography on Sephadex G-25 and Sephadex G-200
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using DEAE-cellulose column chromatography
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using protamine sulfate treatment, ammonium sulfate fractionation and treatment with calcium phosphate gel
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA is cloned from a human fetal library, library is constructed in a modified pBluescript II SK+ vector, cDNA insert is sequenced
cloning of lys2, the cloned gene encodes a functional alpha-aminoadipate reductase as shown by complementation of a Penicillium chrysogenum lys2 mutant, the aminoacid sequence shows strong homology with the alpha-aminoadipate reductase encoded by lys2 genes of Candida albicans, Schizosaccharomyces pombe, Saccharomyces cerevisiae and Penicillium chrysogenum
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cloning of the LYS2 gene
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encoded by two different genes, LYS2 and LYS5
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expression in Escherichia coli as an active enzyme. Exhibits significant alpha-aminoadipate reductase activity without the addition of CoA and Lys7p PPTase from Schizosaccharomyces pombe
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heterlogous expressed in Escherichia coli
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LYS2 gene cloned
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LYS2 gene codes for alpha-aminoadipate reductase, construction and use of LYS2 cartridges
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LYS2 gene codes for alpha-aminoadipate reductase, LYS2 genes encodes a protein with 49.9% identity to the Saccharomyces cerevisiae, 51.3% identity to the Schizosaccharomyces pombe and 48.12% identity to the Candida albicans alpha-aminoadipate reductases
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LYS2 gene codes for alpha-aminoadipate reductase, LYS2 ORF exhibits 63% identity at the nucleotide level and 56.2% identity at the aminoacid level to the LYS2 gene of Saccharomyces cerevisiae
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Lys5 and Lys2 cloned from Saccharomyces cerevisiae DNA, overexpressed in Escherichia coli, and purified, Lys5/Lys2 pair is a two component system in which Lys5 covalently primes Lys2, allowing alpha-aminoadipate reductase activity by holo-Lys2 with catalytic cycles of autoaminoacylation and reductive clevage
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one-step homologous recombination in Saccharomyces cerevisiae, expression of the human gene in the yeast rescues the lys5 knockout phenotype
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two genes, lys1+ and lys7+ are required for the synthesis of the enzyme, some regions of the enzyme sequence are similar to the sequence of Saccharomyces cerevisiae, e.g. Schizosaccharomyces pombe enzyme residues 345 through 385, and 449 through 470
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G848K
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enzyme activity not detectable
G874ade/874R/874K
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lys arg double mutation in strain G874 isolated after a second induced mutagenesis in ade mutant G846
G905K
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enzyme activity detectable
G982K
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enzyme activity detectable
G983ade/983K
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lys mutation in strain G983 isolated after a second induced mutagenesis in ade mutant G846, enzyme activity detectable
G984K
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very low activity
G985K
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enzyme activity not detectable
C125I
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mutant enzyme shows no alpha-aminoadipate reductase activity
D126E
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mutant enzyme shows no alpha-aminoadipate reductase activity
D94E
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mutant enzyme shows no alpha-aminoadipate reductase activity
E173D
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mutant enzyme shows no alpha-aminoadipate reductase activity
F93W
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mutant enzyme shows no alpha-aminoadipate reductase activity
F95W
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mutant enzyme shows no alpha-aminoadipate reductase activity
G124A
-
mutant enzyme shows no alpha-aminoadipate reductase activity
G79A
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mutant enzyme shows no alpha-aminoadipate reductase activity
G910A
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mutant enzyme shows no alpha-aminoadipate reductase activity
K172R
-
mutant enzyme shows no alpha-aminoadipate reductase activity
K177R
-
mutant enzyme shows no alpha-aminoadipate reductase activity
N96D
-
mutant enzyme shows no alpha-aminoadipate reductase activity
P81A
-
mutant enzyme shows no alpha-aminoadipate reductase activity
R80K
-
mutant enzyme shows no alpha-aminoadipate reductase activity
S913A
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mutant enzyme shows no alpha-aminoadipate reductase activity
S913T
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mutant enzyme shows no alpha-aminoadipate reductase activity
additional information
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alpha-AASA dehydrogenase deficiency is characterised by increases of alpha-aminoadipic semialdehyde in urine, plasma and cerebrospinal fluid
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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alpha-AASA dehydrogenase deficiency results in pyridoxine dependent epilepsy. Patients show pathogenic mutations in the ALDH7A1 gene. Increase of alpha-AASA in urine of patients with alpha-AASA dehydrogenase deficiency makes this biomarker preferable towards the measurement of pipecolic acid, which shows non-specificity
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