ALDH2 gene plays a major role in alcohol metabolism. ALDH2 codes for a detoxifying enzyme in the mitochondrial aldehyde dehydrogenase family. [R]

Aldehyde dehydrogenase is the second enzyme in alcohol metabolism. Aldehyde dehydrogenase catalyzes the chemical transformation from acetaldehyde (cancer causing) to a less harmful byproduct called acetic acid.[R]

The highest concentration of ALDH2 and therefore the main site of alcohol metabolism is found in the liver.[R]

Small quantities of ALDH2 can be found in the pancreas, brain, and gastrointestinal tract.[R]

The effects of alcohol consumption depend on the rate of ethanol metabolism.[R]

Alternative splicing results in transcript variants.[R]

Variations, or alleles, in the ALDH2 enzyme affect the rate of ethanol metabolism. These variants can be either active or inactive.[R]

Alda-1 is a molecule that activates the catalytic activity of ALDH2 by initiating a physiological response. Disulfiram (Antabuse) is the only FDA-approved drug that inhibits ALDH2 and the chemical transformation of acetaldehyde to acetic acid.[R]

Mutations such as ALDH2*2  inactivate the enzyme. Individuals with ALDH2*2 metabolize acetaldehyde at very low concentrations and toxic byproduct builds up in their bloodstream.

ALDH*2 causes acute alcohol intoxication.[R]

Increased exposure to acetaldehyde in individuals with ALDH*2 is associated with nausea, headaches, facial flushing, systematic dermatitis, liver damage, alcohol induced respiratory reactions, increased risk of cancer, non-insulin-dependent diabetes, and osteoporosis. [R, R2, R3, R4]

ALDH2 variants are unevenly distributed among ethnic groups. This explains why some ethnic groups have higher or lower rates of alcohol-related problems.[R]

Ashkenazi Jews often show adverse symptoms of ALDH2*2 enzymatic activity.[R]

While most Europeans have 2 active enzyme variants, approximately 36% of Eastern Asians carry one or two copies of the ALDH2*2 inactive variant.[R]

There are remarkably higher frequencies of acute alcohol intoxication and alcohol dependence among Eastern Asians than other populations due to reduced ALDH2 enzymatic activity.[R]

Individuals with 1 copy of the ALDH2*2 allele can metabolize ethanol at a higher frequency than individuals with 2 copies of of ALDH2*2, encouraging them to continue consumption and heightening their risk of developing alcoholism and esophageal cancer.[R]

ALDH2 also appears to metabolize toxic environmental compounds such as those found in car exhaust and tobacco smoke.[R]

Exposures to ALDH-inhibiting pesticides were associated with 2- to 6-fold increases in PD risk; genetic variation in ALDH2 exacerbated PD risk in subjects exposed to ALDH-inhibiting pesticides.

ALDH inhibition appears to be an important mechanism through which environmental toxicants contribute to PD pathogenesis, especially in genetically vulnerable individuals, suggesting several potential interventions to reduce PD occurrence or slow or reverse its progression. (R)

     From NCBI Gene: Acute alcohol sensitivity

     From NCBI Gene: This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of Orientals have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among Orientals than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2011]

The following transcription factors affect gene expression:

• PPAR-alpha
• GR
• GR-alpha
• GR-beta
• p53
• PPAR-gamma1
• PPAR-gamma2

Molecular Function:

• Aldehyde Dehydrogenase (Nad) Activity
• Aldehyde Dehydrogenase [Nad(P)+] Activity
• Electron Carrier Activity
• Aldehyde Dehydrogenase

Biological Processes:

• Carbohydrate Metabolic Process
• Alcohol Metabolic Process
• Ethanol Catabolic Process
• Ethanol Oxidation

Drug Bank:

• Amyl Nitrite
• Benzyl Alcohol
• Disulfiram
• Nitric Oxide
• Nitroglycerin
• Guanidine