protein
Succinate-semialdehyde dehydrogenase, mitochondrial
Gene
ALDH5A1
Organism
Homo sapiens(9606)
Length
535 aa
Mass
57,215 Da
ALDH5A1 (succinate-semialdehyde dehydrogenase, mitochondrial) catalyzes a critical step in gamma-aminobutyric acid (GABA) degradation, the final enzymatic reaction converting succinic semialdehyde to succinate (UniProt: P51649). The enzyme is localized to mitochondria and plays a central role in GABAergic neurotransmission homeostasis.
ALDH5A1 is associated with succinic semialdehyde dehydrogenase deficiency (SSADHD; MIM 271980), a rare inborn error of GABA metabolism characterized by accumulation of 4-hydroxybutyric acid and clinical manifestations including developmental delay, intellectual disability, ataxia, seizures, and behavioral disturbances (UniProt: P51649). The enzyme's function in neurotransmitter metabolism positions it within GABAergic and mitochondrial bioenergetic pathways.
In Alzheimer's disease, ALDH5A1 is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of +0.13 across analyzed subcellular fractions in human post-mortem brain, suggesting altered GABA metabolism may accompany AD pathology. This modest upregulation may reflect compensatory changes in inhibitory neurotransmitter catabolism or mitochondrial stress responses in AD brain.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
not detected
S3
+0.135
Mean log₂FC across detected fractions: +0.1349 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
Disease associations
Succinic semialdehyde dehydrogenase deficiencySSADHD
A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, intellectual disability, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.
Sources
Last updated 5/8/2026, 6:34:29 AM