ALDH2, or Aldehyde Dehydrogenase 2, is an enzyme that plays a significant role in the human body. Enzymes are specialized proteins that act as catalysts, accelerating chemical reactions without being consumed in the process. ALDH2 helps facilitate certain metabolic processes. While its functions are diverse, it is particularly known for its involvement in how the body processes certain substances.
Understanding ALDH2 and Its Primary Role
ALDH2 is a member of the aldehyde dehydrogenase family of enzymes. Its primary function involves breaking down harmful aldehydes into less toxic substances. Specifically, ALDH2 is highly effective at converting acetaldehyde, a toxic byproduct produced during alcohol metabolism, into acetate. This conversion is a key step in the body’s detoxification pathway for alcohol.
The metabolic pathway begins when alcohol is converted into acetaldehyde by the enzyme alcohol dehydrogenase (ADH). Acetaldehyde is a harmful compound that can damage cells and tissues. ALDH2, primarily located in the mitochondria of liver cells, then processes this acetaldehyde, transforming it into acetate, a less harmful substance. Acetate can then be broken down into carbon dioxide and water for elimination.
The Genetic Basis of Alcohol Sensitivity
A specific genetic variation, the ALDH22 allele, can significantly affect ALDH2 enzyme function, leading to a less functional or even inactive enzyme. The ALDH22 allele causes a change in the enzyme’s structure, which distorts its binding site and reduces its activity. Individuals who are heterozygous for ALDH22 may have 10% to 45% of normal enzyme activity, while those homozygous for the variant may have as little as 1% to 5% activity.
When ALDH2 is less effective due to this genetic variant, acetaldehyde accumulates in the body after alcohol consumption. This buildup of acetaldehyde causes a range of unpleasant symptoms, commonly referred to as the “alcohol flush reaction” or “Asian glow.” These symptoms include facial flushing, lightheadedness, nausea, headaches, dizziness, and an increased heart rate. The ALDH22 variant is particularly prevalent in East Asian populations, affecting 30-49% of individuals in countries like South Korea, China, Japan, and Taiwan. It is estimated that about 8% of the world’s population carries this dysfunctional ALDH2 variant.
Long-Term Health Risks of ALDH2 Deficiency
Individuals with ALDH2 deficiency who continue to consume alcohol face increased risks due to prolonged exposure to elevated acetaldehyde levels. Acetaldehyde is classified as a Group 1 carcinogen by the World Health Organization, known to cause cancer in humans. This toxic compound can damage DNA and proteins within cells.
The accumulation of acetaldehyde significantly increases the risk of certain cancers, including esophageal, head and neck, and gastric cancers. For example, someone with the ALDH22 variant who drinks moderately may have a risk of esophageal cancer 40 to 80 times higher than a person without the mutation who consumes the same amount. The risk is dose-dependent, meaning greater alcohol intake translates to an even higher risk. ALDH2 deficiency is also associated with an increased risk of cardiovascular issues, such as coronary artery disease and stroke.
ALDH2’s Broader Protective Functions
Beyond its primary role in alcohol metabolism, ALDH2 also provides broader protective functions by detoxifying other harmful aldehydes produced within the body. These aldehydes can arise from sources like environmental pollution, smoking, and oxidative stress.
ALDH2 helps clear these toxic compounds, safeguarding cellular integrity by preserving mitochondrial membrane function and inhibiting harmful intracellular pathways. This enzyme’s activity is involved in protecting against damage in conditions like heart disease and neurodegenerative disorders such as Alzheimer’s and Parkinson’s. Enhancing ALDH2 activity may protect neurons from oxidative stress and other forms of damage, potentially slowing the progression of these conditions.