UniProtKB:P47738

UniProtKB entry for mouse Aldh2/mitochondrial aldehyde dehydrogenase

Aldh2 is a mitochondrial matrix aldehyde dehydrogenase with EC 1.2.1.3 activity.

"CATALYTIC ACTIVITY: Reaction=an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+); EC=1.2.1.3"
Aldh2 acts in the final step of ethanol degradation.

"PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2."
Aldh2 is required for cellular formaldehyde clearance and localizes to the mitochondrial matrix.

"Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. SUBCELLULAR LOCATION: Mitochondrion matrix."

file:mouse/Aldh2/Aldh2-deep-research-falcon.md

Falcon deep research report for mouse Aldh2

Falcon verifies the target as mouse Aldh2/UniProt P47738 and summarizes the core function as mitochondrial NAD+-dependent oxidation of acetaldehyde and other aldehydes.

"Mouse **Aldh2** (UniProt P47738) encodes **mitochondrial aldehyde dehydrogenase 2 (ALDH2)**, an NAD\(^+\)-dependent aldehyde-oxidizing enzyme that catalyzes conversion of **acetaldehyde to acetate/acetic acid** and also detoxifies multiple **reactive lipid-derived aldehydes** (notably **4-hydroxynonenal (4-HNE)** and **acrolein**)."
Falcon places the core activity in mitochondria and summarizes the main physiological ethanol and reactive-aldehyde substrates.

"ALDH2 is described as the **second enzyme in oxidative alcohol metabolism**, converting **acetaldehyde to acetic acid**, and is also capable of oxidizing lipid aldehydes including **acrolein (ACR), 4-HNE, and MDA**."

Gene Ontology annotation through association of InterPro records with GO terms

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:3996732

Mouse mitochondrial aldehyde dehydrogenase isozymes: purification and molecular properties.

Purified two mitochondrial ALDH isozymes from mouse liver. AHD-5 (=Aldh2) has very low Km for acetaldehyde (0.2 µM), confirming it as the primary high-affinity acetaldehyde-oxidizing enzyme. Both isozymes are dimers with distinct kinetic properties.

PMID:12693930

Crystal structure of eta-crystallin: adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens.

Crystal structure of eta-crystallin (class 1 ALDH) reveals a well-ordered NAD binding site conserved across ALDH classes 1 and 2, providing structural basis for NAD binding annotation of ALDH2.

PMID:14651853

Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria.

Proteomic survey detected Aldh2 in mitochondria from mouse brain, heart, kidney, and liver, confirming mitochondrial localization across multiple tissues.

PMID:18614015

A mitochondrial protein compendium elucidates complex I disease biology.

MitoCarta compendium identified Aldh2 as a mitochondrial protein by mass spectrometry across 14 mouse tissues, further confirming mitochondrial localization.

PMID:19356968

Ethanol metabolism in ALDH2 knockout mice--blood acetate levels.

ALDH2 knockout mice showed significantly higher blood ethanol and acetaldehyde and lower blood acetate after ethanol dosing, directly demonstrating Aldh2 is required for normal ethanol catabolism via acetaldehyde oxidation to acetate.

PMID:21720390

SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity.

ALDH2 is a direct SIRT3 substrate. SIRT3-mediated deacetylation of ALDH2 increases binding of acetaminophen toxic metabolites and enzyme inactivation, linking ALDH2 post-translational regulation to xenobiotic hepatotoxicity.

PMID:26711020

Ethanol and acetaldehyde differentially alter extracellular dopamine and serotonin in Aldh2-knockout mouse dorsal striatum: A reverse microdialysis study.

In Aldh2-KO mice, acetaldehyde perfusion into dorsal striatum decreased extracellular dopamine and serotonin levels, while this effect was absent in WT mice. This demonstrates indirect neurotransmitter effects of acetaldehyde accumulation due to Aldh2 deficiency.