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Enzyme Nomenclature
Information on EC 1.2.1.24 - succinate-semialdehyde dehydrogenase (NAD+)
for references in articles please use BRENDA:EC1.2.1.24
Word Map on EC 1.2.1.24
- 1.2.1.24
-
aldhs
-
gamma-hydroxybutyric
-
4-hydroxybutyric
- propionaldehyde
-
ssadhd
- aldh4a1
-
neurometabolic
- trans-4-hydroxy-2-nonenal
- medicine
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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EC NUMBER 
COMMENTARY 
1.2.1.24
-
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RECOMMENDED NAME
GeneOntology No.
succinate-semialdehyde dehydrogenase (NAD+)
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
succinate semialdehyde + NAD+ + H2O = succinate + NADH + 2 H+
compulsory-order mechanism, NAD+ is the first substrate to bind to the enzyme and NADH is the last product to dissociate from it
-
succinate semialdehyde + NAD+ + H2O = succinate + NADH + 2 H+
compulsory ordered mechanism where NAD+ binds first followed by succinate semialdehyde
-
succinate semialdehyde + NAD+ + H2O = succinate + NADH + 2 H+
sequential ordered Bi-Bi reaction mechanism
succinate semialdehyde + NAD+ + H2O = succinate + NADH + 2 H+
sequential ordered Bi-Bi reaction mechanism
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-
succinate semialdehyde + NAD+ + H2O = succinate + NADH + 2 H+
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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
succinate-semialdehyde:NAD+ oxidoreductase
This enzyme participates in the degradation of glutamate and 4-aminobutyrate. It is similar to EC 1.2.1.79 [succinate-semialdehyde dehydrogenase (NADP+)], and EC 1.2.1.16 [succinate-semialdehyde dehydrogenase (NAD(P)+)], but is specific for NAD+.
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CAS REGISTRY NUMBER
COMMENTARY
9028-95-9
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
complete sequence of cDNA clone H46643 with C538/transition; naturally occuring missense variants, which may significantly contribute to inter-individual variation of SSADH activity, possibly influencing endogenous level of 4-aminobutyric acid and 4-hydroxybutyric acid
SwissProt
single nucleotide polymorphism in the coding sequence as well as in the exons and the 5'-regulatory region of the succinic semialdehyde dehydrogenase gene can not be related to idiopathic generalized epilepsy or abnormal photoparoxysomal response
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
additional information
-
human SSADH intrinsic regulatory mechanism, redox-switch modulation, by which large conformational changes are brought about in the catalytic loop through disulfide bonding, enzyme molecular structure, overview
malfunction
-
SSADH enzyme activity is deficient in patients with gamma-hydroxybutyric aciduria
malfunction
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at approximately postnatal day 16-22 SSADH-deficient mice display ataxia and loss of motor control, and develop generalized seizures leading to rapid death by the fourth week of life. D-2-hydroxyglutarate and 4,5-dihydroxyhexanoic acid are elevated in SSADH-deficient mice. SSADH-deficient mice demonstrate a 20% reduction in the ethanolamine glycerophospholipid content as compared to wild type littermates while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) are not affected
malfunction
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mutation of gene ALDH5A1 with amino acid exchange K301E is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive inherited metabolic disorder of the catabolism of the neurotransmitter gamma-aminobutyric acid (GABA) with a very variable clinical phenotype ranging from mild intellectual disability to severe neurological defects. The disorder results in the accumulation of gamma-hydroxybutyrate in the brain, 30fold increased level compared to wild-type. No SSADH enzyme activity is detected in the patient's lymphoblasts
metabolism
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SSADH plays an essential role in the metabolism of the inhibitory neurotransmitter c-aminobutyric acid
metabolism
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under normal physiological conditions, SSADH works in tandem with GABA transaminase to convert the carbon backbone of gamma-aminobutyric acid to succinate, the latter a source of energy within the tricarboxylic acid cycle. SSADH, in brain, is the major aldehyde dehydrogenase responsible for 4-hydroxy-trans-2-nonenal disposition, but only a minor contributor to its metabolism in liver
metabolism
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under normal physiological conditions, SSADH works in tandem with GABA transaminase to convert the carbon backbone of gamma-aminobutyric acid to succinate, the latter a source of energy within the tricarboxylic acid cycle. SSADH, in brain, is the major aldehyde dehydrogenase responsible for 4-hydroxy-trans-2-nonenal disposition, but only a minor contributor to its metabolism in liver
metabolism
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the enzyme is involved in the metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2,5-dioxopentanoate + NAD+ + H2O
?
no activity in presence of NADP+
-
-
?
2-carboxybenzaldehyde + NAD+ + H2O
2-carboxybenzoate + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
2-hydroxybenzaldehyde + NAD+ + H2O
2-hydroxybenzoate + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
2-nitrobenzaldehyde + NAD+ + H2O
2-nitrobenzoate + NADH + H+
about 3% activity compared to succinate semialdehyde
-
-
?
2-phenylacetaldehyde + NAD+ + H2O
2-phenylbenzoate + NADH + H+
about 5% activity compared to succinate semialdehyde
-
-
?
2-tolualdehyde + NAD+ + H2O
2-carboxytoluene + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
4-hydroxy-trans-2-nonenal + NAD+
?
-
elevated levels of 4-hydroxy-trans-2-nonenal are implicated in the pathogenesis of numerous neurodegenerative disorders. Succinate-semialdehyde dehydrogenase is the predominant oxidizing enzyme for 4-hydroxy-trans-2-nonenal but only contributes a portion of the total oxidizing activity in liver mitochondria
-
-
?
alpha-ketoglutaric semialdehyde + NAD+ + H2O
alpha-ketoglutarate + NADH
-
-
-
?
alpha-ketoglutaric semialdehyde + NADP+ + H2O
alpha-ketoglutarate + NADPH
-
-
-
?
betaine aldehyde + NAD+ + H2O
2-trimethylammonioacetate + NADH
-
-
-
?
glyoxylic acid + NAD+ + H2O
2-phenylbenzoate + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
iso-butanal + NAD+ + H2O
? + NADH + H+
less than 10% activity compared to succinate semialdehyde
-
-
?
iso-butanal + NAD+ + H2O
isobutanoate + NADH + H+
-
less than 10% activity compared to succinate semialdehyde
-
-
?
iso-pentanal + NAD+ + H2O
? + NADH + H+
about 2% activity compared to succinate semialdehyde
-
-
?
iso-pentanal + NAD+ + H2O
isopentanoate + NADH + H+
-
less than 5% activity compared to succinate semialdehyde
-
-
?
m-carboxybenzaldehyde + NAD+ + H2O
m-carboxybenzoate + NADH + H+
-
-
-
?
m-methylcarboxybenzaldehyde + NAD+ + H2O
m-methylcarboxybenzoate + NADH + H+
-
-
-
?
m-nitrobenzaldehyde + NAD+ + H2O
m-nitrobenzoate + NADH
-
4.3% of the activity with succinate semialdehyde
-
-
?
malonate semialdehyde + NAD+ + H2O
malonate + NADH + 2 H+
-
3.8% of the activity with succinate semialdehyde
-
-
?
n-butanal + NAD+ + H2O
butanoic acid + NADH + 2 H+
-
about 11% of the rate with succinic semialdehyde
-
-
?
3-carboxybenzaldehyde + NAD(P)+ + H2O
3-carboxybenzoate + NAD(P)H + H+
-
-
-
-
?
3-carboxybenzaldehyde + NAD(P)+ + H2O
3-carboxybenzoate + NAD(P)H + H+
-
-
-
?
3-carboxybenzaldehyde + NAD+ + H2O
3-carboxybenzoate + NADH + H+
about 20% activity compared to succinate semialdehyde
-
-
?
3-carboxybenzaldehyde + NAD+ + H2O
3-carboxybenzoate + NADH + H+
-
about 35% activity compared to succinate semialdehyde
-
-
?
3-hydroxybenzaldehyde + NAD+ + H2O
3-hydroxybenzoate + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
3-hydroxybenzaldehyde + NAD+ + H2O
3-hydroxybenzoate + NADH + H+
about 2% activity compared to succinate semialdehyde
-
-
?
3-hydroxybenzaldehyde + NAD+ + H2O
3-hydroxybenzoate + NADH + H+
-
about 3% activity compared to succinate semialdehyde
-
-
?
3-methoxy-benzaldehyde + NAD+ + H2O
3-methoxy-benzoate + NADH + H+
about 5% activity compared to succinate semialdehyde
-
-
?
3-methoxy-benzaldehyde + NAD+ + H2O
3-methoxy-benzoate + NADH + H+
-
about 10% activity compared to succinate semialdehyde
-
-
?
3-methylbenzaldehyde + NAD+ + H2O
3-methylbenzoate + NADH + H+
about 3% activity compared to succinate semialdehyde
-
-
?
3-methylbenzaldehyde + NAD+ + H2O
3-methylbenzoate + NADH + H+
-
about 10% activity compared to succinate semialdehyde
-
-
?
3-nitrobenzaldehyde + NAD+ + H2O
3-nitrobenzoate + NADH + H+
about 20% activity compared to succinate semialdehyde
-
-
?
3-nitrobenzaldehyde + NAD+ + H2O
3-nitrobenzoate + NADH + H+
-
about 15% activity compared to succinate semialdehyde
-
-
?
4-carboxybenzaldehyde + NAD(P)+ + H2O
4-carboxybenzoate + NAD(P)H + H+
-
-
-
-
?
4-carboxybenzaldehyde + NAD(P)+ + H2O
4-carboxybenzoate + NAD(P)H + H+
-
-
-
?
4-carboxybenzaldehyde + NAD+ + H2O
4-carboxybenzoate + NADH + H+
about 10% activity compared to succinate semialdehyde
-
-
?
4-carboxybenzaldehyde + NAD+ + H2O
4-carboxybenzoate + NADH + H+
-
about 65% activity compared to succinate semialdehyde
-
-
?
4-hydroxy-trans-2-nonenal + NAD+ + H2O
4-hydroxy-trans-2-nonenoate + NADH + H+
-
-
-
-
?
4-hydroxy-trans-2-nonenal + NAD+ + H2O
4-hydroxy-trans-2-nonenoate + NADH + H+
-
-
-
-
?
4-hydroxy-trans-2-nonenal + NAD+ + H2O
4-hydroxy-trans-2-nonenoate + NADH + H+
-
-
-
-
?
4-methoxy-benzaldehyde + NAD+ + H2O
4-methoxy-benzoate + NADH + H+
about 1% activity compared to succinate semialdehyde
-
-
?
4-methoxy-benzaldehyde + NAD+ + H2O
4-methoxy-benzoate + NADH + H+
-
about 5% activity compared to succinate semialdehyde
-
-
?
4-nitrobenzaldehyde + NAD+ + H2O
4-nitrobenzoate + NADH + H+
about 15% activity compared to succinate semialdehyde
-
-
?
4-nitrobenzaldehyde + NAD+ + H2O
4-nitrobenzoate + NADH + H+
-
about 30% activity compared to succinate semialdehyde
-
-
?
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
-
2.3% of the activity with succinate semialdehyde
-
-
?
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
about 5% activity compared to succinate semialdehyde
-
-
?
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
-
about 10% activity compared to succinate semialdehyde
-
-
?
benzaldehyde + NAD+ + H2O
benzoate + NADH + H+
about 5% activity compared to succinate semialdehyde
-
-
?
benzaldehyde + NAD+ + H2O
benzoate + NADH + H+
-
about 30% activity compared to succinate semialdehyde
-
-
?
glutaric semialdehyde + NAD+ + H2O
glutarate + NADH
-
13% of the activity with succinate semialdehyde
-
-
?
glutaric semialdehyde + NAD+ + H2O
glutarate + NADH
-
25% of the activity with succinate semialdehyde
-
-
?
methyl 3-formylbenzoate + NAD+ + H2O
3-(methoxycarbonyl)benzoate + NADH + H+
about 20% activity compared to succinate semialdehyde
-
-
?
methyl 3-formylbenzoate + NAD+ + H2O
3-(methoxycarbonyl)benzoate + NADH + H+
-
about 45% activity compared to succinate semialdehyde
-
-
?
methyl 4-formylbenzoate + NAD+ + H2O
4-(methoxycarbonyl)benzoate + NADH + H+
about 15% activity compared to succinate semialdehyde
-
-
?
methyl 4-formylbenzoate + NAD+ + H2O
4-(methoxycarbonyl)benzoate + NADH + H+
-
about 30% activity compared to succinate semialdehyde
-
-
?
n-butanal + NAD+ + H2O
butanoate + NADH + H+
about 10% activity compared to succinate semialdehyde
-
-
?
n-butanal + NAD+ + H2O
butanoate + NADH + H+
-
less than 60% activity compared to succinate semialdehyde
-
-
?
n-hexanal + NAD+ + H2O
hexanoate + NADH + H+
less than 10% activity compared to succinate semialdehyde
-
-
?
n-hexanal + NAD+ + H2O
hexanoate + NADH + H+
-
about 110% activity compared to succinate semialdehyde
-
-
?
n-octanal + NAD+ + H2O
n-octanoate + NADH + H+
less than 10% activity compared to succinate semialdehyde
-
-
?
n-octanal + NAD+ + H2O
n-octanoate + NADH + H+
-
less than 80% activity compared to succinate semialdehyde
-
-
?
n-pentanal + NAD+ + H2O
n-pentanoate + NADH + H+
less than 20% activity compared to succinate semialdehyde
-
-
?
n-pentanal + NAD+ + H2O
n-pentanoate + NADH + H+
-
100% activity
-
-
?
p-nitrobenzaldehyde + NAD+ + H2O
p-nitrobenzoate + NADH
-
6.5% of the activity with succinate semialdehyde
-
-
?
propanal + NAD+ + H2O
propanoate + NADH + H+
less than 10% activity compared to succinate semialdehyde
-
-
?
propanal + NAD+ + H2O
propanoate + NADH + H+
-
less than 20% activity compared to succinate semialdehyde
-
-
?
propionaldehyde + NAD+ + H2O
propionate + NADH
-
5% of the activity with succinate semialdehyde
-
-
?
succinate semialdehyde + NAD(P)+ + H2O
succinate + NAD(P)H + H+
-
-
-
-
?
succinate semialdehyde + NAD(P)+ + H2O
succinate + NAD(P)H + H+
cysteine 311 and glutamic acid 277 are likely candidates for the active site residues directly involved in catalysis
-
-
?
succinate semialdehyde + NAD(P)+ + H2O
succinate + NAD(P)H + H+
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by growth on gamma-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
last enzyme in catabolism of 4-aminobutyric acid. Human SSADH deficiency results in 4-hydroxybutyric aciduria, an autosomal recessive disorder due to an accumulation of 4-aminobutyric acid and 4-hydroxybutyric acid in the CNS
-
-
ir
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme of agmatine degradation
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by growth on gamma-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by succinate semialdehyde, functions in the oxidation of succinate semialdehyde during growth on both 4-hydroxyphenylacetate and 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by succinate semialdehyde, functions in the oxidation of succinate semialdehyde during growth on both 4-hydroxyphenylacetate and 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme may play an important role, not only in metabolizing succinate semialdehyde but also in oxidation of aromatic aldehydes in the soil environment
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
induced by pyridine, the enzyme is involved in the degradation of pyridine
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
reverse reaction proceeds at 1/1230 of the rate of the forward eaction
-
-
ir
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is involved in the catabolism of the neurotransmitter 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
-
-
-
-
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
-
-
-
ir
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
the enzyme is specific for the substrates
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
the enzyme is specific for the substrates
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
no activity in presence of NADP+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
enzyme of the gamma-aminobutyrate shunt required to restrict levels of reactive oxygen intermediates in plants
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
100% activity with succinate semialdehyde
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
100% activity with succinate semialdehyde
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
20% of the activity with NAD+
-
-
-
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
reduction rate is only a few percent of that of NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
activity with NAD+ is 10times higher than with NADP+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
activity with NAD+ is 10times higher than with NADP+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
reaction with NADP+ is 13% of the activity with NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
activity with NAD+ is about 7fold higher than activity with NADP+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH
-
activity with NAD+ is about 7fold higher than activity with NADP+
-
-
ir
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
-
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
NAD+ is the more efficient coenzyme compared to NADP+, but the preference is not exclusive
-
-
?
additional information
?
-
no activity with formaldehyde, o-nitrobenzaldehyde, o-carboxybenzaldehyde, o-tolualdehyde, p-tolualdehyde, o-methoxybenzaldehyde, p-methoxybenzaldehyde o-hydroxybenzaldehyde, m-hydroxybenzaldehyde, phenylacetaldehyde and glyoxylic acid
-
-
-
additional information
?
-
-
no substrate: formaldehyde, acetaldehyde, glyoxal, glyoxalate, propanal, glutaraldehyde, benzaldehyde, and anisaldehyde
-
-
-
additional information
?
-
-
no substrate: glyoxylic acid, formic acid, formaldehyde, acetaldehyde, glyoxal, furfural and acrolein
-
-
-
additional information
?
-
deficiency of succinate semialdehyde dehydrogenase is a rare autosomal recessively inherited metabolic disorder that results in acumulation of 4-hydroxybutyrate. Functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency
-
-
-
additional information
?
-
-
ALDH5A1 plays an important role as a gamma-aminobutyric acid catabolic enzyme and potentially as a detoxifying enzyme involved in aldehyde scavenging
-
-
-
additional information
?
-
no activity towards 2-methoxybenzaldehyde, and 4-tolualdehyde
-
-
-
additional information
?
-
-
no activity towards 2-methoxybenzaldehyde, 2-nitrobenzaldehyde, 2-carboxybenzaldehyde, 2-tolualdehyde, 4-tolualdehyde, 2-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, 2-phenylacetaldedyde, and glyoxylic acid
-
-
-
additional information
?
-
formaldehyde, betaine aldehyde and benzaldehyde can not serve as substrates
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxy-trans-2-nonenal + NAD+
?
-
elevated levels of 4-hydroxy-trans-2-nonenal are implicated in the pathogenesis of numerous neurodegenerative disorders. Succinate-semialdehyde dehydrogenase is the predominant oxidizing enzyme for 4-hydroxy-trans-2-nonenal but only contributes a portion of the total oxidizing activity in liver mitochondria
-
-
?
4-hydroxy-trans-2-nonenal + NAD+ + H2O
4-hydroxy-trans-2-nonenoate + NADH + H+
-
-
-
-
?
4-hydroxy-trans-2-nonenal + NAD+ + H2O
4-hydroxy-trans-2-nonenoate + NADH + H+
-
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by growth on gamma-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
Q8N3W7
last enzyme in catabolism of 4-aminobutyric acid. Human SSADH deficiency results in 4-hydroxybutyric aciduria, an autosomal recessive disorder due to an accumulation of 4-aminobutyric acid and 4-hydroxybutyric acid in the CNS
-
-
ir
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme of agmatine degradation
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by growth on gamma-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by succinate semialdehyde, functions in the oxidation of succinate semialdehyde during growth on both 4-hydroxyphenylacetate and 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is induced by succinate semialdehyde, functions in the oxidation of succinate semialdehyde during growth on both 4-hydroxyphenylacetate and 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme may play an important role, not only in metabolizing succinate semialdehyde but also in oxidation of aromatic aldehydes in the soil environment
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
induced by pyridine, the enzyme is involved in the degradation of pyridine
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH
-
enzyme is involved in the catabolism of the neurotransmitter 4-aminobutyrate
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
A2R4V5
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
-
enzyme of the gamma-aminobutyrate shunt required to restrict levels of reactive oxygen intermediates in plants
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
Q9SAK4
-
-
-
?
additional information
?
-
P51649
deficiency of succinate semialdehyde dehydrogenase is a rare autosomal recessively inherited metabolic disorder that results in acumulation of 4-hydroxybutyrate. Functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency
-
-
-
additional information
?
-
-
ALDH5A1 plays an important role as a gamma-aminobutyric acid catabolic enzyme and potentially as a detoxifying enzyme involved in aldehyde scavenging
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
NAD+ is the more efficient coenzyme compared to NADP+, but the preference is not exclusive
NAD+
-
-
NADP+
-
cofactor; reduction rate is only a few percent of that of NAD+
NADP+
is also accepted as coenzyme substrate but leads to 7fold lower reaction rates compared to NAD+ at saturating succinate semialdehyde concentrations
additional information
-
human SSADH is active in the reduced state but not in the oxidized state because of disulfide bonding between Cys340 and Cys342 residues. Oxidation induces a large conformational change in the dynamic catalytic loop that consists of 11 residues, including the two cysteines that connect helix alpha8 and strand beta13. As a result, the loop blocks both substrate succinate semialdehyde and cofactor NAD+ binding
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-dimethylaminoazobenzene-4-iodoacetamide
-
time-dependent loss of activity, pseudo first-order kinetics. The inhibitor binds to a cysteine residue or near its active site. Inactivation is prevented by preincubation with succinate semialdehyde, but not by preincubation with coenzyme NAD+
o-phthalaldehyde
-
binding of 10 mol per mol of enzyme results in irreversible loss of activity
4-hydroxybenzaldehyde
linear dead-end inhibition, competitive versus succinate semialdehyde, uncompetitive versus NAD+
N-formylglycine
-
4 mM, 40% inhibition, reversible, competitive with respect to succinate semialdehyde, uncompetitive with respect to NAD+
NADH
product inhibition, competitive versus NAD+, uncompetitive versus succinate semialdehyde
NADH
-
NADH is a strong competitive inhibitor with respect to NAD+ and behaves as a non-competitive inhibitor with respect to succinate semialdehyde
NADH
-
competitive with respect to NAD+; mixed with respect to succinate semialdehyde
pyridoxal 5'-phosphate
-
catalytic function is modulated by binding of pyridoxal-5'-phosphate to specific Lys347 residue at or near the coenzyme-binding site of the protein, NAD+ protects from inactivation
succinate semialdehyde
substrate inhibition, uncompetitive versus NAD+
succinate semialdehyde
-
inhibition by the succinate semialdehyde substrate is starting already at a concentration as low as 0.02 mM
succinate semialdehyde
inhibition by the succinate semialdehyde substrate is starting already at a concentration as low as 0.02 mM
succinate semialdehyde
the enzyme loses more than 80% of its enzymatic potential at 0.5 mM and shows 8% residual activity at 3 mM succinate semialdehyde
succinate semialdehyde
-
substrate inhibition, uncompetitive with respect to NAD+
succinate semialdehyde
-
the enzyme loses more than 80% of its enzymatic potential at 0.5 mM and shows 8% residual activity at 3 mM succinate semialdehyde
additional information
-
no inhibition by 0.1 mM trans-2-hexenal and 0.1 mM crotonaldehyde
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
gene yneI is responsible for NAD+/NADP+-SSADH activity. The gene is induced by succinate semialdehyde
-
2-mercaptoethanol
-
loss of about 50% of original acitivity after exhaustive dialysis, renaturation in presence of 2-mercaptoethanol
2-mercaptoethanol
-
requirement of sulfhydryl protective reagent, maximal activity with 10 mM to 0.1 M dithiothreitol or mercaptoethanol
dithiothreitol
-
requirement of sulfhydryl protective reagent, maximal activity with 10 mM to 0.1 M dithiothreitol or mercaptoethanol
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1035
3-(methoxycarbonyl)benzoate
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0163
Glutaraldehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
0.218
methyl 3-formylbenzoate
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0331
3-carboxybenzaldehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.1418
3-carboxybenzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0502
3-Nitrobenzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.287
3-Nitrobenzaldehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0151
4-carboxybenzaldehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0312
4-carboxybenzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.115
4-carboxybenzaldehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.1668
4-carboxybenzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.156
4-nitrobenzaldehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.1612
4-nitrobenzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
2.797
acetaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
3.16
acetaldehyde
-
mutant enzyme R166K, at 37°C, in 40 mM sodium phosphate, pH 7.4
4.3
acetaldehyde
-
wild type enzyme, at 37°C, in 40 mM sodium phosphate, pH 7.4
4.5
acetaldehyde
-
mutant enzyme R166H, at 37°C, in 40 mM sodium phosphate, pH 7.4
4.82
acetaldehyde
-
mutant enzyme R166E, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.011
alpha-Ketoglutaric semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
0.0159
alpha-Ketoglutaric semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NADP+. 25°C
0.167
benzaldehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.061
n-Butanal
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.323
n-Butanal
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0253
n-Hexanal
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.107
n-Hexanal
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0514
n-octanal
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.137
n-octanal
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.0287
n-Pentanal
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.096
n-Pentanal
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.035
NAD+
-
mutant enzyme R166E, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.0433
NAD+
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.044
NAD+
-
mutant enzyme R166A, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.063
NAD+
-
mutant enzyme R166H, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.081
NAD+
-
mutant enzyme R166K, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.227
NAD+
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
125
NAD+
-
50 microM succinate semialdehyde, 3 mM NAD+, 0.1 M sodium diphosphate pH 8.5, 25°C
0.616
NADP+
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
1.212
propanal
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
1.622
propanal
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.001
succinate semialdehyde
-
pH and temperature not specified in the publication
0.00247
succinate semialdehyde
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.00256
succinate semialdehyde
-
in 100 mM Na2HPO4/NaH2PO4 buffer, 1 mM dithiothreitol, at pH 8.5 and 22°C
0.003
succinate semialdehyde
-
pH and temperature not specified in the publication
0.0109
succinate semialdehyde
-
mutant enzyme R166K, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.013
succinate semialdehyde
-
wild type enzyme, at 37°C, in 40 mM sodium phosphate, pH 7.4
0.0385
succinate semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
0.62
succinate semialdehyde
-
mutant enzyme R166E, at 37°C, in 40 mM sodium phosphate, pH 7.4
1.13
succinate semialdehyde
-
mutant enzyme R166H, at 37°C, in 40 mM sodium phosphate, pH 7.4
1.6
succinate semialdehyde
-
mutant enzyme R166A, at 37°C, in 40 mM sodium phosphate, pH 7.4
6.3
succinate semialdehyde
-
50 microM succinate semialdehyde, 3 mM NAD+, 0.1 M sodium diphosphate pH 8.5, 25°C
additional information
additional information
kinetics and kinetic mechanism, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
12.3
Glutaraldehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
12.3
alpha-Ketoglutaric semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NADP+. 25°C
51.2
alpha-Ketoglutaric semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
31.7
succinate semialdehyde
1 mM EDTA, 1 mM 2-mercaptoethanol, 66.7 mM potassium phosphate pH 7.2, 1.5 mM NAD+. 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.37
4-hydroxybenzaldehyde
pH 9.0, 37°C, versus succinate semmialdehyde
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
8.6
9.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.5
at pH 8.5 MalE-DmSSADH is 10fold more active than at pH 6.0
7 - 10
8 - 9
8 - 10
-
pH 8.0: about 40% of maximal activity, pH 10.0: about 55% of maximal activity
8.5 - 10
-
pH 8.5: about 45% of maximal activity, pH 10.0: about 70% of maximal activity
8.7 - 10.5
-
pH 8.7: about 50% of maximal activity, pH 10.5: about 75% of maximal activity
7 - 10
-
pH 7.0: about 40% of maximal activity, pH 10.0: about 35% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
optimal expression of pMalc2x-DmSSADH in Escherichia coli TB1
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
SSADH is widely expressed throughout most brain regions, although a particularly strong expression is observed in the primary and secondary motor cortex, the amygdala, and the basal ganglia
-
SSADH is widely expressed throughout most brain regions, although a particularly strong expression is observed in the primary and secondary motor cortex, the amygdala, and the basal ganglia
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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PDB
SCOP
CATH
ORGANISM
UNIPROT
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
52000
55400
98000
145000
160000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homotetramer
homotrimer
3 * 50000, SDS-PAGE; 3 * 51500, calculated from sequence
tetramer
additional information
additional information
-
human SSADH is active in the reduced state but not in the oxidized state because of disulfide bonding between Cys340 and Cys342 residues. Oxidation induces a large conformational change in the dynamic catalytic loop that consists of 11 residues, including the two cysteines that connect helix alpha8 and strand beta13. As a result, the loop blocks both substrate succinate semialdehyde and cofactor NAD+ binding. Human SSADH activity is regulated by redox-switch modulation, which depends on reversible intra-disulfide binding to the dynamic catalytic loop. Simulations, and protein transformation and configuration modelling to explain the dynamic redox modulation, method optimization, detailed overview
additional information
-
4-aminobutyrate aminotransferase and succinate semialdehyde dehydrogenase form a stable enzymatic complex under in vivo conditions
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.2
-
with wild type enzyme, similar activity is observed with pH 7.4 and 8.2, only 10% of the pH 7.4 activity is observed when the pH is reduced to pH 6.0, substitution with a lysine removes the pH sensitivity whereas the R166H mutant enzyme has higher activity at pH 6.0 than at pH 8.0
697282
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
-
pH 7.4, 8 min, complete inactivation. Mercaptoethanol stabilizes for 20 min or longer
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
NAD+ and mercaptoethanol effectively protect from auto-oxidation. NAD+ does not prevent auto-oxidation in presence of urea
-
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
when reduced wild type SSADH is treated with hydrogen peroxide, the protein is almost completely inactivated and recovers its activity when the environment is switched back to a reduced state
-
710898
when reduced wild type SSADH is treated with hydrogen peroxide, the protein is almost completely inactivated and recovers its activity when the environment was switched back to a reduced state
-
710898
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM sodium diphosphate buffer, pH 7.2, 14 mM 2-mercaptoethanol, 25% v/v glycerol, 2-3 months, retains 80-85% of the activity
-
-20°C, purified native enzyme, 100 mM diphosphate, pH 8.0, 14 mM 2-mercaptoethanol, 20% glycerol, loss of 50% activity witin 5 days
0°C, 100 mM sodium phosphate, pH 8.5, 1mM DTT, 43% glycerol, 3 years
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged YneI dehydrogenase purified from cell extracts with HiTrap affinity columns
-
native enzyme 9fold from mycelia by ammonium sulfate fractionation, hydrophobic interaction and anion exchange chromatography
Ni-affinity chromatography
Ni2+-NTA agarose column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli M15 cells
expression in Escherichia coli as His-tag fusion protein
gene ALDH5A1, screening and genotyping, DNA and amino acid sequence determination and analysis
-
into vectors pQE30 and into pMalc2x. Expression in Escherichia coli strains M15 and TB1
PCR product cloned into pCR2.1-Topo. Open reading frame ligated into vector QE30. Overexpressed in Escherichia coli M15. Subcloned into pMALc2x and expressed in Escherichia coli TB1
into vectors pQE30 and into pMalc2x. Expression in Escherichia coli strains M15 and TB1
-
into vectors pQE30 and into pMalc2x. Expression in Escherichia coli strains M15 and TB1
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E277K
charge inversion, which results in recombinant protein totally devoid of detectable SSADH activity
E277Q
concomitant loss of the negative charge, which results in recombinant protein totally devoid of detectable SSADH activity
A237S
A273S
C223R
C223Y
C340A
-
inactive mutant that cannot form a disulfide bond even under strong reducing conditions
C342A
-
catalytically functional mutant that cannot form a disulfide bond even under strong reducing conditions
C93F
G176R
G268E
G36R
G409D
G533R
H180Y
K301E
-
naturally occuring homozygous missense mutation c.901A>G, inactive mutant, the mutation leads to semialdehyde dehydrogenase (SSADH) deficiency disorder, phenotype overview. Mutation K301E most likely leads to a loss of NAD+ binding and a predicted decrease in the free energy by 6.67 kcal/mol suggesting a severe destabilization of the protein. Structure-based in silico modeling of the mutant protein
N255S
N335K
P182L
P382L
R166A
-
the mutant enzyme shows no activity towards acetaldehyde and decreased activity and higher KM for succinate semiacetaldehyde
R166E
-
the mutant enzyme shows almost no activity towards acetaldehyde and decreased activity and higher KM for succinate semiacetaldehyde
R166H
-
the mutant has KM for succinate semiacetaldehyde of 800fold greater than the wild type enzyme, while the VMAX for this mutant is 11.3fold less than wild type for succinate semiacetaldehyde
R166K
-
the mutant has KM for succinate semiacetaldehyde of 8fold greater than the wild type enzyme, while the VMAX for this mutant is 2.5fold less than wild type for succinate semiacetaldehyde
additional information
A237S
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 65% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
A273S
naturally occuring missense variant expressed in HEK293 cells, 65.1% of the SSADH activity of the wild-type enzyme
C223R
-
missense mutation associated with a dramatic reduction of enzyme activity
C223Y
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 5% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
C93F
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 3% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G176R
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, less than 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G268E
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, less than 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G36R
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 87% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G36R
naturally occuring missense variant expressed in HEK293 cells, 86.7% of the SSADH activity of the wild-type enzyme
G36R
-
the slight activity reduction displayed by the G36R variant can be attributed to altered mitochondrial targeting, as the amino acid change lies within the mitochondrial leader sequence
G409D
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, less than 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G533R
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, less than 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
H180Y
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 83% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
H180Y
naturally occuring missense variant expressed in HEK293 cells, 82.5% of the SSADH activity of the wild-type enzyme
N255S
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 17% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
N335K
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
P182L
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 5% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
P182L
naturally occuring missense variant expressed in HEK293 cells, 47.6% of the SSADH activity of the wild-type enzyme
P382L
-
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, 2% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
additional information
-
yneI knockout mutant shows strongly inhibited growth compared to the wild-type
additional information
-
yneI knockout mutant shows strongly inhibited growth compared to the wild-type
-
additional information
Aldh5a1-/- mice show abnormalities of respiratory chain function. Hippocampus and cortex are primary targets for neurodegeneration
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
medicine
SSADH (Aldh5a1) deficiency is a rare autosomal recessive disease. Hippocampal and cortical dysfunction in Aldh5a1-/- brain, but no evidence that accumulating key metabolites of SSADH deficiency directly induce impairment of energy metabolism
medicine
-
succinic semialdehyde dehydrogenase deficient patients show widespread reduction in benzodiazepine receptor binding on [(11)C]-flumazenil-positron emission tomography
additional information
-
in the world population, the c.538C variant of SSADH is proceeding to replace the ancestral c.538T, shared with primates. A significant correlation between the frequencies of the derived alleles in SSADH and microcephalin, which show concerted changes worldwide and, at least in Asian populations, also on a restricted geographical scale
additional information
-
genomic copy of the SSADH gene is devoid of introns. Multiple SSADH gene copies are present in the genome
additional information
genomic copy of the SSADH gene contains two introns. Multiple SSADH gene copies are present in the genome
additional information
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yneI, responsible for NAD+/NADP+-dependent SSADH activity, plays a unique physiological role in the general nitrogen metabolism of Escherichia coli. The yneI gene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The yneI-encoded activity functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde
additional information
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yneI, responsible for NAD+/NADP+-dependent SSADH activity, plays a unique physiological role in the general nitrogen metabolism of Escherichia coli. The yneI gene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The yneI-encoded activity functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde
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LINKS TO OTHER DATABASES (specific for EC-Number 1.2.1.24)