Psychiatry related information on ALDH2

• BACKGROUND: The single genetic factor most strongly correlated with reduced alcohol consumption and incidence of alcoholism is a naturally occurring variant of mitochondrial aldehyde dehydrogenase (ALDH2) [1].

High impact information on ALDH2

• The mitochondrial (mt) aldehyde dehydrogenase (ALDH2) in liver has been considered to play a major role in the detoxification of alcohol in humans [2].
• The relative sizes of the tunnels also suggest why the bulky alcohol aversive drug disulfiram reacts more rapidly with ALDH1 than ALDH2 [3].
• The active site of ALDH2 is divided into two halves by the nicotinamide ring of NAD+ [1].
• The E487K variant of ALDH2 is found in approximately 50% of the Asian population, and is associated with a phenotypic loss of ALDH2 activity in both heterozygotes and homozygotes [1].
• ALDH2-deficient individuals exhibit an averse response to ethanol consumption, which is probably caused by elevated levels of blood acetaldehyde [1].

Associations of ALDH2 with chemical compounds

• All-trans retinal fits into the active-site pocket of ALDH1, but not into the pocket of ALDH2 [3].
• The selective ALDH2 inhibitor, daidzin (0.1 mM), increased the EC50 of GTN to 7.47+/-0.93 microM [4].

References