1.2.1.24: succinate-semialdehyde dehydrogenase (NAD+)
This is an abbreviated version!
For detailed information about succinate-semialdehyde dehydrogenase (NAD+), go to the full flat file.
Word Map on EC 1.2.1.24
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1.2.1.24
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aldhs
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gamma-hydroxybutyric
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ssadhd
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4-hydroxybutyric
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propionaldehyde
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trans-4-hydroxy-2-nonenal
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aldh4a1
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akr7a2
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ssadh-deficient
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medicine
- 1.2.1.24
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aldhs
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gamma-hydroxybutyric
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ssadhd
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4-hydroxybutyric
- propionaldehyde
- trans-4-hydroxy-2-nonenal
- aldh4a1
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akr7a2
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ssadh-deficient
- medicine
Reaction
Synonyms
aldehyde dehydrogenase 5a1, ALDH5A, ALDH5A1, alphaKGSA dehydrogenase, dehydrogenase, succinate semialdehyde, NAD(+)-dependent succinic semialdehyde dehydrogenase, SSADH, SSADH-I, SSADH/ALDH5A1, SSALDH, SSO1629, succinate semialdehyde dehydrogenase, succinate semialdehyde:NAD+ oxidoreductase, succinic semialdehyde dehydrogenase, succinyl semialdehyde dehydrogenase, YneI dehydrogenase
ECTree
1.2.1.24 succinate-semialdehyde dehydrogenase (NAD+)Advanced search results
results (
results (Engineering
Engineering on EC 1.2.1.24 - succinate-semialdehyde dehydrogenase (NAD+)
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PROTEIN VARIANTS 
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
A237S/T423S
naturally occuring mutation, the mutant shows about 70% reduced activity compared to wild-type
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
G176R/H180Y
naturally occuring mutation, the p.G176R change, alone or in combination with p.H180Y, causes the abolishment of enzyme activity
G176R/H180Y/A237S/T423S
naturally occuring mutation, an Italian SSADHD patient shows heterozygosity for four missense mutations: c.526G>A (p.G176R), c.538C>T (p.H180Y), c.709G>T (p.A237S) and c.1267A>T (p.T423S). The p.G176R change, alone or in combination with p.H180Y, causes the abolishment of enzyme activity. Clinical and cognitive evaluations, phenotype, overview
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
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the mutant enzyme shows no activity towards acetaldehyde and decreased activity and higher KM for succinate semiacetaldehyde
R166E
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the mutant enzyme shows almost no activity towards acetaldehyde and decreased activity and higher KM for succinate semiacetaldehyde
R166H
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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
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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
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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
G176R
the mutant shows less than 1% activity compared to the wild type enzyme
G176R
naturally occuring mutation, the p.G176R change, alone or in combination with p.H180Y, causes the abolishment of enzyme activity. Amino acid replacements G176R and H180Y are located in the same beta-segment that is at the interface between the monomers. The introduction of the positive charges of arginines, in presence of the bulky sidechains of tyrosines, could inhibit the correct tetramer assembly, thus causing instability
G268E
missense mutation of patient with succinate semialdehyde dehydrogenase deficiency, less than 1% of the succinate semialdehyde dehydrogenase activity of the wild-type enzyme
G268E
the mutant shows less than 1% activity compared to 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
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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
G409D
the mutant shows less than 1% activity compared to 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
G533R
the mutant shows less than 1% activity compared to 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
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yneI knockout mutant shows strongly inhibited growth compared to the wild-type
additional information
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yneI knockout mutant shows strongly inhibited growth compared to the wild-type
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additional information
lowest stability for the tetramer constituted by G176R/H180Y monomers and the highest stability for that constituted by A237S/T423S monomers. The combination of the two double mutant alleles produces a synergic negative effect on SSADH enzyme activity and stability, thus resulting in SSADHD phenotype
additional information
Aldh5a1-/- mice show abnormalities of respiratory chain function. Hippocampus and cortex are primary targets for neurodegeneration
additional information
aldh5a1-/- (SSADHD) mice and their genetic controls (aldh5a1+/+) are exposed to either a 4% (w/w) glutamine-containing diet or a glutamine-free diet from conception until postnatal day 30. The test diet increases hepatic glutamate in both genotypes, decreases glutamine in aldh5a1+/+ but not in aldh5a1-/-, but has no effect on GABA. Dried bloodspot analyses show significantly elevated GABA in mutants (approximately 800% above controls) and decreased glutamate (approximately 25%), but no glutamine difference with controls. Glutamine supplementation does not impact blood GABA but significantly increased glutamine and glutamate in both genotypes indicating systemic exposure to dietary glutamine. Ataxia and pronounced hyperactivity are observed in aldh5a1-/- mice but remain unchanged by the diet intervention. Glutamine supplementation improves peripheral but not central glutamine deficiency in experimental SSADHD. Murine SSADHD presents with dramatic changes in amino acid levels including a significant elevation in brain GABA, one of the major inhibitory neurotransmitters, a moderate increase in excitatory neurotransmitter glutamate, and a very significant decrease in brain glutamine, the metabolic precursor of glutamate. Phenotype, overview
additional information
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aldh5a1-/- (SSADHD) mice and their genetic controls (aldh5a1+/+) are exposed to either a 4% (w/w) glutamine-containing diet or a glutamine-free diet from conception until postnatal day 30. The test diet increases hepatic glutamate in both genotypes, decreases glutamine in aldh5a1+/+ but not in aldh5a1-/-, but has no effect on GABA. Dried bloodspot analyses show significantly elevated GABA in mutants (approximately 800% above controls) and decreased glutamate (approximately 25%), but no glutamine difference with controls. Glutamine supplementation does not impact blood GABA but significantly increased glutamine and glutamate in both genotypes indicating systemic exposure to dietary glutamine. Ataxia and pronounced hyperactivity are observed in aldh5a1-/- mice but remain unchanged by the diet intervention. Glutamine supplementation improves peripheral but not central glutamine deficiency in experimental SSADHD. Murine SSADHD presents with dramatic changes in amino acid levels including a significant elevation in brain GABA, one of the major inhibitory neurotransmitters, a moderate increase in excitatory neurotransmitter glutamate, and a very significant decrease in brain glutamine, the metabolic precursor of glutamate. Phenotype, overview
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