Aldehyde dehydrogenase (ALDH) is a family of enzymes playing a fundamental role in human health by detoxifying harmful substances. These enzymes convert reactive aldehydes into less toxic carboxylic acids. This crucial conversion process helps eliminate potentially damaging compounds from the body, underscoring ALDH’s importance in maintaining overall well-being.
The Body’s Detoxifier
ALDH enzymes function by catalyzing the oxidation of aldehydes, transforming them into carboxylic acids. The ALDH family is a superfamily, with at least nineteen different ALDH genes identified in the human genome, each encoding a specific enzyme isoform. These diverse ALDH enzymes are distributed throughout the body, found in various tissues such as the liver, brain, kidneys, and heart, highlighting their widespread detoxification responsibilities. They neutralize a range of aldehydes, including those produced naturally during normal metabolic processes and those encountered from environmental sources. This broad action protects cells and tissues from aldehyde-induced damage.
Alcohol’s Aftermath
ALDH plays a role in the metabolism of alcohol. When alcohol is consumed, it is first converted into acetaldehyde by enzymes like alcohol dehydrogenase (ADH), primarily in the liver. Acetaldehyde is a highly toxic compound, responsible for many unpleasant hangover symptoms, such as nausea, headaches, and facial flushing.
ALDH enzymes, particularly ALDH2, then rapidly convert this toxic acetaldehyde into acetate, a less harmful substance. The efficient functioning of ALDH2 is crucial for preventing the buildup of acetaldehyde and mitigating its toxic effects. An impaired ALDH2 can lead to prolonged exposure to acetaldehyde, intensifying hangover symptoms and posing greater health risks.
Genetic Differences and Health
Genetic variations exist within the aldehyde dehydrogenase family, with the ALDH2 gene being particularly notable. A common variant, known as ALDH22, is prevalent in a substantial portion of the global population, especially among individuals of East Asian descent, affecting approximately 40% of this demographic. This genetic alteration leads to a less active or almost inactive ALDH2 enzyme.
Individuals carrying the ALDH22 variant experience a rapid accumulation of acetaldehyde after consuming alcohol, even in small amounts. This buildup triggers “alcohol flush syndrome” or “Asian flush,” characterized by facial redness, increased heart rate, dizziness, and nausea. Beyond these immediate discomforts, prolonged or regular alcohol consumption in individuals with this variant is associated with an elevated risk of certain cancers, including esophageal cancer.
Beyond Alcohol: Broader Roles in Health
While its role in alcohol metabolism is well-documented, aldehyde dehydrogenase enzymes perform numerous other functions. They are instrumental in detoxifying a wide array of aldehydes generated within the body from normal biological processes, referred to as endogenous aldehydes. These include compounds formed during lipid peroxidation and during the metabolism of neurotransmitters.
ALDH enzymes also protect the body from exogenous aldehydes, which are harmful compounds originating from external sources, such as pollutants, components of cigarette smoke, and various industrial chemicals. By converting these toxic substances into harmless carboxylic acids, ALDH contributes to cellular protection against oxidative stress and broader environmental toxins. This protective capacity of ALDH has implications for various health conditions, including neurodegenerative diseases such as Parkinson’s and Alzheimer’s, certain types of cancer unrelated to alcohol consumption, and cardiovascular health.