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The ALDH2 gene is about 44 kbp in length and contains at least 13 exons which encode 517 amino acid residues. Except for the signal NH2-terminal peptide, which is absent in the mature enzyme, the amino acid sequence deduced from the exons coincided with the reported primary structure of human liver ALDH2.
Aldehyde dehydrogenase is a polymorphic enzyme [3] responsible for the oxidation of aldehydes to carboxylic acids. [3] There are three different classes of these enzymes in mammals: class 1 (low K m, cytosolic), class 2 (low K m, mitochondrial), and class 3 (high K m, such as those expressed in tumors, stomach, and cornea).
ALDH2, which has a lower K M for acetaldehydes than ALDH1 and acts predominantly in the mitochondrial matrix, is the main enzyme in acetaldehyde metabolism and has three genotypes. A single point mutation (G → A) at exon 12 of the ALDH2 gene causes a replacement of glutamate with lysine at residue 487, resulting in the ALDH2K enzyme. [8]
Aldehyde dehydrogenase 1 family, member A2, also known as ALDH1A2 or retinaldehyde dehydrogenase 2 (RALDH2), is an enzyme that in humans is encoded by the ALDH1A2 gene. [ 5 ] [ 6 ] Function
It is encoded by 5 exons, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules.
ALDH2 pictured on the left, is an enzyme which breaks down acetaldehyde. [20] [21] Regions highlighted in yellow are structural and allow ALDH2 to fold properly. [20] [21] The region highlighted in red can vary between individuals (right). [22] Individuals who have a G in their DNA will have normal folding and function of ALDH2. [20]
The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons , or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster.
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]