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Information on EC 1.2.1.31 - L-aminoadipate-semialdehyde dehydrogenase and Organism(s) Homo sapiens and UniProt Accession P49419

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EC Tree
IUBMB Comments
(S)-2-amino-6-oxohexanoate undergoes a spontaneous dehydration forming the cyclic (S)-2,3,4,5-tetrahydropyridine-2-carboxylate, which serves as a substrate for the hydrogenation reaction.
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This record set is specific for:
Homo sapiens
UNIPROT: P49419
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
aldh7a1, antiquitin, alpha-ar, aldehyde dehydrogenase 7a1, aasadh, alpha-aar, lys1p, alpha-aminoadipic semialdehyde dehydrogenase, alpha-aasa dehydrogenase, alpha-aminoadipate semialdehyde dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aldehyde dehydrogenase 7A1
-
alpha-AASA dehydrogenase
-
alpha-aminoadipic semialdehyde dehydrogenase
-
antiquitin
-
2-aminoadipate semialdehyde dehydrogenase
-
-
-
-
2-aminoadipic 6-semialdehyde dehydrogenase
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2-aminoadipic semialdehyde dehydrogenase
-
-
-
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alpha-AASA dehydrogenase
-
-
alpha-aminoadipate-semialdehyde dehydrogenase
-
-
-
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alpha-aminoadipic semialdehyde dehydrogenase
-
-
Alpha-AR
-
-
-
-
antiquitin
-
-
dehydrogenase, aminoadipate semialdehyde
-
-
-
-
human U26
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L-alpha-aminoadipate delta-semialdehyde oxidoreductase
-
-
-
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L-alpha-aminoadipate delta-semialdehyde:NAD oxidoreductase
-
-
-
-
L-alpha-aminoadipate delta-semialdehyde:nicotinamide adenine dinucleotide oxidoreductase
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-
-
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L-aminoadipate-semialdehyde dehydrogenase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
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oxidation
reduction
SYSTEMATIC NAME
IUBMB Comments
L-2-aminoadipate-6-semialdehyde:NAD(P)+ 6-oxidoreductase
(S)-2-amino-6-oxohexanoate undergoes a spontaneous dehydration forming the cyclic (S)-2,3,4,5-tetrahydropyridine-2-carboxylate, which serves as a substrate for the hydrogenation reaction.
CAS REGISTRY NUMBER
COMMENTARY hide
9067-87-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-2-amino-6-oxohexanoate + NAD+ + H2O
L-2-aminoadipate + NADH + H+
show the reaction diagram
-
-
-
?
(S)-2-amino-6-oxohexanoate + NADP+ + H2O
L-2-aminoadipate + NADPH + H+
show the reaction diagram
-
-
-
?
alpha-aminoadipate semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
-
-
-
?
alpha-aminoadipic semialdehyde + NAD+ + H2O
alpha-aminoadipic acid + NADH + H+
show the reaction diagram
-
-
-
?
L-2-aminoadipate 6-semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
-
-
-
?
L-2-aminoadipate 6-semialdehyde + NAD+ + H2O
L-2-aminoadipate + NADH
show the reaction diagram
-
-
-
ir
L-alpha-aminoadipate-semialdehyde + NAD(P)+ + H2O
L-alpha-aminoadipate + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-2-amino-6-oxohexanoate + NAD+ + H2O
L-2-aminoadipate + NADH + H+
show the reaction diagram
-
-
-
?
(S)-2-amino-6-oxohexanoate + NADP+ + H2O
L-2-aminoadipate + NADPH + H+
show the reaction diagram
-
-
-
?
alpha-aminoadipate semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
-
-
-
?
L-2-aminoadipate 6-semialdehyde + NAD(P)+ + H2O
L-2-aminoadipate + NAD(P)H + H+
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
-
-
NAD+
-
-
pyrroloquinoline quinone
PQQ
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cu2+
-
stimulates
Mg2+
-
stimulates
Mn2+
-
stimulates
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Disulfiram
0.01 mM
EDTA
-
-
FeCl3
-
-
KCN
-
strongly inhibits, 75% inhibition
Pb(NO3)2
-
-
Sodium diphosphate
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
10 mM, activates
dithiothreitol
-
10 mM, activates
L-cysteine
-
10 mM, activates
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.181
L-2-aminoadipate 6-semialdehyde
-
-
0.454
NAD+
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00077
-
cytosol fraction
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
in 0.2 M Tris-glycine buffer containing 5 mM beta-mercaptoethanol, L-alpha-aminoadipate-semialdehyde reduction
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
the catalytically active oligomer of ALDH7A1 is assembled on demand in response to cofactor availability
malfunction
-
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AL7A1_HUMAN
539
0
58487
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
dimeric enzyme, gel filtration and mass spectrometry
184000
tetrameric enzyme, gel filtration and mass spectrometry
222000
tetrameric enzyme, about, sequence calculation
additional information
wild-type ALDH7A1 in the absence of any substrates is subjected to SEC-MALS-SAXS analysis using three nominal loading concentrations in the range of 2-8 mg/ml (18-72 microM by dimer Mr). Results of the MALS experiment show the average in-solution Mr increases from 134 kDa to 158 kDa with increasing protein load concentration, consistent with a concentration-dependent dimer-tetramer equilibrium. For reference, the dimer Mr is 111 kDa. Wild-type ALDH7A1 in the absence of any substrates is subjected to SEC-MALS-SAXS analysis using three nominal loading concentrations in the range of 2-8 mg/ml (18-72 microM by dimer Mr). Results of the MALS experiment show the average in-solution Mr increases from 134 kDa to 158 kDa with increasing protein load concentration, consistent with a concentration-dependent dimer-tetramer equilibrium
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
2 * 54000, quantitative sedimentation analysis
tetramer
4 * 54000, quantitative sedimentation analysis
additional information
ALDH7A1 forms a dimer-of-dimers tetramer both in crystallo and in solution. NAD+-binding promotes assembly of the ALDH7A1 tetramer and enhances ALDH7A1 tetramerization at micromolar enzyme concentrations. The apoenzyme is mainly dimeric. NAD+-bound ALDH7A1 is predominantly tetrameric. The tetramer is the active form of the enzyme. The catalytically active oligomer of ALDH7A1 is assembled on demand in response to cofactor availability. The major peaks correspond to Mr of 110 kDa and 184 kDa, which are both below the theoretical Mr of the tetramer (222 kDa), consistent with an intermediate exchange regime in which free dimer exists in solution simultaneously with a dimer-tetramer equilibrium. The minor species at 2.7S (54 kDa) likely represents a monomer (theoretical Mr of 56 kDa)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
homolog of the yeast Lys5 gene encodes alpha-aminoadipate dehydrogenase phosphopantetheinyl transferase activity, 26% identity and 44% similarity to the yeast counterpart
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
alpha-AASA dehydrogenase deficiency is characterised by increases of alpha-aminoadipic semialdehyde in urine, plasma and cerebrospinal fluid
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 0.02 mM potassium phosphate buffer, pH 7.0, 5 mM 2-mercaptoethanol, 3 months
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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
one-step homologous recombination in Saccharomyces cerevisiae, expression of the human gene in the yeast rescues the lys5 knockout phenotype
-
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chang, Y.F.; Ghosh, P.; Rao, V.V.
L-pipecolic acid metabolism in human liver: L-alpha-aminoadipate delta-semialdehyde oxidoreductase
Biochim. Biophys. Acta
1038
300-305
1990
Homo sapiens
Manually annotated by BRENDA team
Praphanphoj, V.; Sacksteder, K.A.; Gould, S.J.; Thomas, G.H.; Geraghty, M.T.
Identification of the.alpha-Aminoadipic Semialdehyde Dehydrogenase-Phosphopantetheinyl Transferase Gene, the Human Ortholog of the Yeast LYS5 Gene
Mol. Genet. Metab.
72
336-342
2001
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Jil, C.; Xu, Y.; Xu, J.; Dai, J.; Wu, Q.; Wu, M.; Zou, X.; Sun, L.; Gu, S.; Xie, Y.; Mao, Y.
Cloning and characterization of a novel human homolog of mouse U26, a putative PQQ-dependent AAS dehydrogenase
Mol. Biol. Rep.
32
47-53
2005
Homo sapiens (Q4L235), Homo sapiens
Manually annotated by BRENDA team
Marchitti, S.A.; Deitrich, R.A.; Vasiliou, V.
Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase
Pharmacol. Rev.
59
125-150
2007
Homo sapiens (P49419)
Manually annotated by BRENDA team
Struys, E.A; Jakobs, C.
Alpha-aminoadipic semialdehyde is the biomarker for pyridoxine dependent epilepsy caused by alpha-aminoadipic semialdehyde dehydrogenase deficiency
Mol. Genet. Metab.
91
405
2007
Homo sapiens
Manually annotated by BRENDA team
Struys, E.A.; Jakobs, C.
Metabolism of lysine in alpha-aminoadipic semialdehyde dehydrogenase-deficient fibroblasts: evidence for an alternative pathway of pipecolic acid formation
FEBS Lett.
584
181-186
2010
Homo sapiens
Manually annotated by BRENDA team
Korasick, D.A.; White, T.A.; Chakravarthy, S.; Tanner, J.J.
NAD+ promotes assembly of the active tetramer of aldehyde dehydrogenase 7A1
FEBS Lett.
592
3229-3238
2018
Homo sapiens (P49419)
Manually annotated by BRENDA team
Coughlin, C.R.; Tseng, L.A.; Abdenur, J.E.; Ashmore, C.; Boemer, F.; Bok, L.A.; Boyer, M.; Buhas, D.; Clayton, P.T.; Das, A.; Dekker, H.; Evangeliou, A.; Feillet, F.; Footitt, E.J.; Gospe, S.M.; Hartmann, H.; Kara, M.; Kristensen, E.; Lee, J.; Lilje, R.; Longo, N.; Lunsing, R.J.; Mills, P.; Papadopoulou, M.T.
Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency
J. Inherit. Metab. Dis.
44
178-192
2021
Homo sapiens (P49419)
Manually annotated by BRENDA team