A 25 years old male, flushes and feel ill after drinking small amounts of ethanol in alcoholic beverages. This reaction is due to genetic variation in an enzyme that metabolizes the liver metabolite of alcohol, which is:
First, I need to recall the metabolism of alcohol. Ethanol is first metabolized by alcohol dehydrogenase (ADH) in the liver to acetaldehyde. Acetaldehyde is then broken down by aldehyde dehydrogenase (ALDH) into acetate, which is harmless. If there's a deficiency or genetic variation in ALDH2, acetaldehyde accumulates, leading to symptoms like flushing, nausea, and increased heart rate. This is commonly known as the "alcohol flush reaction" or "Asian flush," which is more prevalent in East Asian populations due to a genetic polymorphism in ALDH2.
The question is pointing out that the enzyme variation is in the liver metabolite of alcohol. Since the main metabolite is acetaldehyde, the enzyme responsible for its metabolism is ALDH2. The correct answer should be ALDH2. The options might be ADH, ALDH, CYP2E1, or maybe another enzyme. The incorrect options would include ADH, which is the first step, but the problem here is the second step. CYP2E1 is another enzyme involved in alcohol metabolism, especially in the context of chronic alcohol use and oxidative stress, but not the primary one for acetaldehyde. So the right answer is ALDH2.
**Core Concept**
The question examines the genetic basis of alcohol intolerance, specifically the enzyme deficiency causing acetaldehyde accumulation. Key enzymes in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2).
**Why the Correct Answer is Right**
Ethanol is first oxidized to acetaldehyde by ADH. Acetaldehyde, a toxic metabolite, is then converted to acetate by **aldehyde dehydrogenase 2 (ALDH2)** in the liver. A common genetic polymorphism (ALDH2*2 allele) leads to reduced ALDH2 activity, causing acetaldehyde accumulation. This triggers flushing, tachycardia, and nausea—symptoms of the "alcohol flush reaction."
**Why Each Wrong Option is Incorrect**
**Option A:** Alcohol dehydrogenase (ADH) deficiency does not cause this reaction. ADH deficiency reduces initial ethanol metabolism, but acetaldehyde levels remain low.
**Option B:** Cytochrome P450 2E1 (CYP2E1) contributes to alcohol oxidation in chronic users but is not the primary enzyme for acetaldehyde metabolism.
**Option C:** Catalase is a minor ethanol-metabolizing enzyme in tissues like the brain; it plays no role in acetaldehyde detoxification in the liver.
**Clinical Pearl / High-Yield Fact**
The ALDH2*2 allele is prevalent in 30–50% of East Asians. Patients with this polymorphism are at higher risk for esophageal cancer from alcohol use due to chronic acetaldehyde toxicity. Always screen for this in patients with alcohol intolerance.
**Correct Answer: B. Aldehyde dehydrogenase (ALDH2)**