Alcohol Metabolism

Related Subjects: | Alcohol Metabolism

🍷 Up to 90% of alcohol consumed is metabolised in the liver. The process involves enzymatic pathways converting ethanol → acetaldehyde (toxic) → acetate (less harmful, excreted as CO₂ + H₂O). ⚠️ Acetaldehyde and reactive oxygen species (ROS) drive much of alcohol’s tissue damage, especially in the liver.

🧬 Pathways of Alcohol Metabolism

• Alcohol Dehydrogenase (ADH) Pathway 🔑 :
  • Primary route in hepatocytes.
  • ADH converts ethanol → acetaldehyde.
  • Acetaldehyde → acetate via ALDH (aldehyde dehydrogenase).
  • Excess acetaldehyde → flushing, nausea, DNA damage, carcinogenicity.
• Microsomal Ethanol-Oxidizing System (MEOS) 🔥 :
  • Activated in chronic heavy drinkers.
  • Cytochrome P450 system (mainly CYP2E1).
  • Generates ROS → lipid peroxidation, mitochondrial injury, hepatocyte apoptosis.
  • Explains why chronic drinkers metabolise alcohol faster but suffer more organ damage.
• Catalase Pathway 🧪 :
  • Minor contribution, uses hydrogen peroxide (H₂O₂).
  • More relevant in brain tissue metabolism of alcohol.

⚖️ Factors Affecting Alcohol Metabolism

• Genetics 🧬 :
  • ADH/ALDH polymorphisms alter metabolism.
  • ALDH2 deficiency (common in East Asians) → flushing, palpitations, ↑ oesophageal cancer risk.
• Gender 🚺 vs 🚹 :
  • Women: lower gastric ADH activity → higher BAC for same intake.
• Age 🎂 :
  • Older adults: slower hepatic metabolism → prolonged effects.
• Food Intake 🍽️ :
  • Delays gastric emptying → lowers peak BAC.
• Chronic Drinking 🍻 :
  • Induces CYP2E1 → faster ethanol clearance, more ROS → ↑ cirrhosis and cancer risk.

🧨 Effects of Alcohol Metabolism

• Acute 🍸 :
  • CNS depression → impaired coordination, judgement.
  • Hangover: acetaldehyde toxicity (headache, nausea, sweating).
• Chronic 🩸 :
  • Liver: fatty change → hepatitis → fibrosis → cirrhosis → hepatocellular carcinoma.
  • Cancer: ↑ risk of oral, oesophageal, liver cancers (acetaldehyde carcinogenicity).
  • Cardiovascular: dilated cardiomyopathy, arrhythmias, hypertension.
  • Neurology: peripheral neuropathy, Wernicke–Korsakoff syndrome (thiamine deficiency).
• Tolerance & Dependence 🔄 :
  • MEOS induction → tolerance (need more alcohol for same effect).
  • Dependence: cravings, withdrawal (tremor, seizures, delirium tremens).

🧪 Diagnosis

• 📊 Blood alcohol concentration (BAC).
• 🩺 Liver function tests (↑ ALT, AST, GGT, bilirubin).
• 📉 MCV and CDT (carbohydrate-deficient transferrin) may indicate chronic misuse.
• 🧾 Screening tools: AUDIT questionnaire, CAGE questions.

💊 Treatment

• Behavioural Therapies 🧠 :
  • CBT, motivational interviewing, relapse prevention, peer support (AA).
• Medications 💊 :
  • Disulfiram → inhibits ALDH → acetaldehyde buildup → unpleasant reaction if alcohol consumed.
  • Naltrexone → reduces cravings (opioid receptor antagonist).
  • Acamprosate → modulates glutamate/GABA → helps maintain abstinence.
• Lifestyle & Medical 🏃‍♂️🥗 :
  • Balanced nutrition, vitamin supplementation (esp. thiamine B1).
  • Detoxification under medical supervision if dependent (prevent seizures/DTs).
  • Rehabilitation programmes, inpatient units if severe.

📚 Summary

Alcohol metabolism mainly occurs via the ADH → ALDH pathway in the liver. Genetics, gender, diet, and chronic intake all influence metabolism. 💡 Key clinical relevance: Acetaldehyde & ROS drive tissue damage → cirrhosis, cancer, neuropathy. Effective management requires a mix of medical, psychological, and lifestyle interventions.