Long-chain-aldehyde dehydrogenase

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]

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]

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.