ALDH5A1, also known as aldehyde dehydrogenase 5 family member A1, is an enzyme that plays a role in the metabolism of certain compounds in the human body. Specifically, ALDH5A1 is responsible for the metabolism of succinic semialdehyde (SSA), a chemical that is an intermediate in the catabolic pathway of gamma-aminobutyric acid (GABA), a neurotransmitter in the central nervous system.

Here are some key points about ALDH5A1:

Role in GABA Metabolism: ALDH5A1 is a mitochondrial enzyme that catalyzes the conversion of SSA to succinic acid, which is part of the citric acid cycle (Krebs cycle) and is involved in energy production. This metabolic pathway is crucial for the regulation of GABA levels in the brain.

Genetic and Clinical Significance: Mutations in the ALDH5A1 gene can lead to a rare metabolic disorder known as succinic semialdehyde dehydrogenase deficiency (SSADH deficiency). In individuals with SSADH deficiency, ALDH5A1 enzyme activity is impaired, resulting in the accumulation of SSA and gamma-hydroxybutyric acid (GHB), both of which are neuroactive substances. This accumulation can lead to various neurological and developmental issues, including intellectual disability, seizures, and behavioral problems.

Therapeutic Considerations: Management of SSADH deficiency typically involves strategies to reduce the levels of SSA and GHB. This may include dietary modifications and medication to help alleviate symptoms. There is ongoing research into potential treatments and interventions for this rare disorder.

Research Significance: ALDH5A1 and the GABA metabolic pathway have relevance in the field of neuroscience and the study of neurotransmitter regulation and brain function. Understanding the genetics and biochemistry of this enzyme is essential for unraveling the mechanisms behind SSADH deficiency and related neurological disorders.

ALDH5A1 is one of several enzymes involved in the metabolism of GABA and its byproducts. The disruption of this metabolic pathway can have significant implications for brain function and overall health, particularly in the context of inborn errors of metabolism like SSADH deficiency.






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Li et al. compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3, and MB-G4), with a focus on genes associated with mitochondria. They used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1, and Metscape.

A total of 668 genes were differentially expressed and the most abundant genes were associated with the cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes ([[ABAT]], [[SOX9]], [[ALDH5A]], [[FOXM1]], [[ABL1]], [[NHLH1]], [[NEUROD1]] and [[NEUROD2]]) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were [[AHCYL1]] and [[SFXN5]] while [[PAICS]] was significantly upregulated in the MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the [[OXPHOS]] complexes, except [[COX6B2]] which was strongly upregulated.
They show the importance of mitochondria and compare their role in the four different medulloblastoma groups
((Li Q, Jia Y, Tang B, Yang H, Yang Q, Luo X, Pan Y. Mitochondrial subtype MB-G3 contains potential novel biomarkers and therapeutic targets associated with prognosis of medulloblastoma. Biomarkers. 2023 Oct 27:1-16. doi: 10.1080/1354750X.2023.2276670. Epub ahead of print. PMID: 37886818.)).