In enzymology, a retinal dehydrogenase, also known as retinaldehyde dehydrogenase (RALDH), catalyzes the chemical reaction converting retinal to retinoic acid. This enzyme belongs to the family of oxidoreductases, specifically the class acting on aldehyde or oxo- donor groups with NAD+ or NADP+ as acceptor groups, the systematic name being retinal:NAD+ oxidoreductase. This enzyme participates in retinol metabolism. The general scheme for the reaction catalyzed by this enzyme is: retinal + NAD+ + H2O retinoic acid + NADH + H+ Structure Retinal dehydrogenase is a tetramer of identical units, consisting of a dimer of dimers. Retinal dehydrogenase monomers are composed of three domains: a nucleotide-binding domain, a tetramerization domain, and a catalytic domain. The dimer can be pictured as an "X" with the dimers forming upper and lower halves that cross over each other. Interestingly, the nucleotide-binding domain of retinal dehydrogenase contains 5 instead of the usual 6 β-strands in the Rossman fold. This appears to be conserved across many aldehyde dehydrogenases. The tetramerization domains lie equatorially along the "X" and the nucleotide binding regions appear on the tips of the "X". Nearby the tetramerization domain lies a 12 Å deep tunnel that gives the substrate access to the key catalytic regions. Residues near the C-terminal end of the catalytic domain have been found to impart specificity in other aldehyde dehydrogenases. Common to many aldehyde dehydrogenases is a catalytic cysteine, which was found to be present in RALDH2, a specific retinal dehydrogenase for which the structure has been solved. Specificity There are three general classes of aldehyde dehydrogenases: class 1 (ALDH1) comprises cytosolic proteins, class 2 (ALDH2) includes mitochondrial proteins, and class 3 (ALDH3) includes tumor-related proteins. ALDH1 enzymes show a high specificity for all-trans retinal and 9-cis retinal in kinetic studies of sheep liver aldehyde dehydrogenases while ALDH2 enzymes show little affinity for retinal and instead appears to be mainly involved in the oxidation of acetaldehyde. The entrance tunnel to the enzyme active site appears to provide the specificity observed in ALDH1 for retinal as a substrate. The size of the tunnel is key in imparting this specificity: the solvent-accessible diameter of the entrance tunnel is 150 Å3 in ALDH1, so the relatively large retinal can be accommodated while the solvent accessible diameter in ALDH2 is only 20 Å3 which limits accessibility to retinal but amply accommodates acetaldehyde. Mechanism The proposed mechanism of retinal dehydrogenase begins with a key cysteine