Long-chain-aldehyde dehydrogenase

Fatty aldehyde dehydrogenase (or long-chain-aldehyde dehydrogenase) is an aldehyde dehydrogenase enzyme that in human is encoded in the ALDH3A2 gene on chromosome 17. Aldehyde dehydrogenase enzymes function to remove toxic aldehydes that are generated by the metabolism of alcohol and by lipid peroxidation.

ALDH3A2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4QGK
Identifiers
Aliases	ALDH3A2, aldehyde dehydrogenase 3 family, member A2, ALDH10, FALDH, SLS, aldehyde dehydrogenase 3 family member A2
External IDs	OMIM: 609523; MGI: 1353452; HomoloGene: 55458; GeneCards: ALDH3A2; OMA:ALDH3A2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p11.2 Start 19,648,136 bp[1] End 19,685,760 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B2|11 37.96 cM Start 61,114,243 bp[2] End 61,158,290 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex skin of thigh skin of hip skin of abdomen hair follicle kidney tubule nipple skin of arm Top expressed in right kidney left lobe of liver gastrula granulocyte mucous cell of stomach lacrimal gland decidua duodenum yolk sac gallbladder More reference expression data BioGPS n/a
Gene ontology Molecular function long-chain-aldehyde dehydrogenase activity long-chain-alcohol oxidase activity medium-chain-aldehyde dehydrogenase activity oxidoreductase activity aldehyde dehydrogenase (NAD+) activity oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor protein binding protein homodimerization activity glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity 3-chloroallyl aldehyde dehydrogenase activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle peroxisome endoplasmic reticulum peroxisomal membrane organelle membrane Biological process peripheral nervous system development sesquiterpenoid metabolic process phytol metabolic process sphingolipid biosynthetic process cellular aldehyde metabolic process central nervous system development epidermis development metabolism fatty acid alpha-oxidation hexadecanal metabolic process lipid metabolism fatty acid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 224 11671 Ensembl ENSG00000072210 ENSMUSG00000010025 UniProt P51648 P47740 RefSeq (mRNA) NM_000382 NM_001031806 NM_001369136 NM_001369137 NM_001369138 NM_001369139 NM_001369146 NM_001369148 NM_007437 NM_001331114 NM_001331115 RefSeq (protein) NP_000373 NP_001026976 NP_001356065 NP_001356066 NP_001356067 NP_001356068 NP_001356075 NP_001356077 NP_001318043 NP_001318044 NP_031463 Location (UCSC) Chr 17: 19.65 – 19.69 Mb Chr 11: 61.11 – 61.16 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

ALDH3A2 belongs to the aldehyde dehydrogenase superfamily and is a membrane-associated protein typically containing 485 residues. The mature protein functions as a dimer. The structure was resolved using X-ray crystallography at 2.1 Angstrom resolution. It contains an element in the C-terminal region referred to as a "gatekeeper" helix, which is adjacent to the membrane-anchored transmembrane domain and the catalytic core. The gatekeeper helix appears to control access of molecular substrates to the catalytic core and allows efficient transit between membranes and catalytic sites.^[5]

Function

ALDH3A2 catalyzes the oxidation of long-chain aliphatic aldehydes into fatty acids. It is known to act on a variety of both saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length, as well as dihydrophytal, a 20-carbon branched chain aldehyde.^[6] It requires NAD+ as a co-factor. The encoded enzyme is responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid. ALD3H2 is expressed in the human liver and has been found to localize the microsome fraction inside the cell.^[7]

At least two alternative splicing isoforms of ALDH3A2 are known to exist. The alternative transcript differs by an additional exon and anchors differently to the endoplasmic reticulum vs. the peroxisome ^[8]

Clinical significance

Mutations and deletions within the ALDH3A2 gene have been widely associated with the autosomal recessive Sjögren-Larsson syndrome, an autosomal recessive neurocutaneous disease.^[9] Multiple mutations have been found in different families, including those that molecularly disrupts the protein dimerization interface or reduces mRNA stability.^{[citation needed]} Absence or insufficiency of ALDH3A2 protein products in mutant cells are known to cause abnormal metabolism of sphingosine 1-phosphate to ether-linked glycerolipids and the abnormal accumulation of lipid precursors.