Recombinant Mouse Aldehyde dehydrogenase 1A1 (Aldh1a1)

Function

Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12851412). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (PubMed:12851412). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (Probable). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:17567582). Also functions downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (By similarity). Also has an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (PubMed:26430123)

Subcellular Location

Cytoplasm, cytosol; Cell projection, axon

Tissue Specificity

Expressed in retina (PubMed:1935685). Expressed in lens and cornea (at protein level) (PubMed:17567582). Expressed by midbrain dopamine neurons (PubMed:26430123)

Subunit

Homotetramer (By similarity). Interacts with PRMT3; the interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity and is independent of the methyltransferase activity of PRMT3 (By similarity)

Pathway

Cofactor metabolism; retinol metabolism

• Rongnoparut P. et al. Isolation and characterization of a cytosolic aldehyde dehydrogenase-encoding cDNA from mouse liver. — Gene (1991)
• Bond S.L. et al. DNA sequence analysis of the cytosolic acetaldehyde dehydrogenase gene (Ahd-2) in mouse strains with variable ethanol preferences. — Biochem. Med. Metab. Biol. (1994)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• McCaffery P. et al. Aldehyde dehydrogenase is a positional marker in the retina. — Development (1991)
• Molotkov A. et al. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. — J. Biol. Chem. (2003)
• Lassen N. et al. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice. — J. Biol. Chem. (2007)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Kim J.I. et al. Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons. — Science (2015)