Individuals without AFS have a glutamic acid at position 487 on the ALDH2 protein, whereas individuals with AFS have a lysine at this position. Using what you determined in 1.2, provide a plausible chemical explanation justifying why the properties of the enzyme could be so drastically altered by this single amino acid substitution. Keep in mind that the enzyme has two substrates, one of which is acetaldehyde and the other is NADH or NAD+

Aldehyde Dehydrogenase 2 (ALDH2) is an enzyme required to eliminate toxins such as acetaldehyde and alcohol, thereby mutations in this protein may be associated with the Alcohol flush syndrome (AFS)

Explanation:

ALDH2 is a protein required for ATP generation by catalyzing the oxidation of aldehydes to carboxylic acids (i.e., oxidation of NADH to NAD+). Mutations in the ALDH2 gene have been associated with the inactive form of this enzyme, and this specific mutation at position 487 alters its enzymatic activity associated with the metabolism of acetaldehyde and alcohol. This amino acid substitution may lead to the active site-directed inactivation of the enzyme.