7yob

Structural highlights

Function

AL1A1_MOUSE 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). Functions also 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). Has also 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).[UniProtKB:P00352]^{[1] [2] [3] [4]}

See Also

• Aldehyde dehydrogenase 3D structures

References

1. ↑ Molotkov A, Duester G. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. J Biol Chem. 2003 Sep 19;278(38):36085-90. doi: 10.1074/jbc.M303709200. Epub 2003, Jul 7. PMID:12851412 doi:http://dx.doi.org/10.1074/jbc.M303709200
2. ↑ Lassen N, Bateman JB, Estey T, Kuszak JR, Nees DW, Piatigorsky J, Duester G, Day BJ, Huang J, Hines LM, Vasiliou V. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice. J Biol Chem. 2007 Aug 31;282(35):25668-76. doi: 10.1074/jbc.M702076200. Epub 2007, Jun 13. PMID:17567582 doi:http://dx.doi.org/10.1074/jbc.M702076200
3. ↑ Kim JI, Ganesan S, Luo SX, Wu YW, Park E, Huang EJ, Chen L, Ding JB. Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons. Science. 2015 Oct 2;350(6256):102-6. doi: 10.1126/science.aac4690. PMID:26430123 doi:http://dx.doi.org/10.1126/science.aac4690
4. ↑ Molotkov A, Duester G. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. J Biol Chem. 2003 Sep 19;278(38):36085-90. doi: 10.1074/jbc.M303709200. Epub 2003, Jul 7. PMID:12851412 doi:http://dx.doi.org/10.1074/jbc.M303709200