Makindo Medical Notes

Related Subjects: |Alcohol Metabolism

Alcohol metabolism is the process by which the body breaks down and eliminates alcohol. The liver plays a central role in metabolizing alcohol, primarily through enzymatic pathways that convert alcohol into less harmful substances that can be excreted from the body.

Pathways of Alcohol Metabolism

• Alcohol Dehydrogenase (ADH) Pathway:
  • The primary pathway for alcohol metabolism in the liver.
  • ADH enzymes convert ethanol to acetaldehyde, a toxic intermediate.
  • Acetaldehyde is then further metabolized by aldehyde dehydrogenase (ALDH) to acetate, which is converted to water and carbon dioxide for excretion.
• Microsomal Ethanol-Oxidizing System (MEOS):
  • An alternative pathway used when alcohol intake is high and ADH is saturated.
  • Involves cytochrome P450 enzymes, particularly CYP2E1.
  • Also converts ethanol to acetaldehyde but produces reactive oxygen species (ROS) as byproducts, which can cause cellular damage.
• Catalase Pathway:
  • A minor pathway that involves the enzyme catalase.
  • Occurs primarily in the liver and other tissues.
  • Converts ethanol to acetaldehyde in the presence of hydrogen peroxide (H₂O₂).

Factors Affecting Alcohol Metabolism

• Genetics:
  • Genetic variations in ADH and ALDH enzymes affect the rate of alcohol metabolism.
  • Some individuals have a variant of ALDH2 (common in East Asian populations) that leads to slower acetaldehyde metabolism, causing alcohol flush reaction.
• Gender:
  • Women generally have lower levels of ADH in the stomach and liver, leading to higher blood alcohol concentrations compared to men.
• Age:
  • Metabolic rate decreases with age, affecting the efficiency of alcohol metabolism.
• Food Intake:
  • Food in the stomach slows the absorption of alcohol, reducing peak blood alcohol concentrations.
• Chronic Alcohol Consumption:
  • Long-term alcohol use induces the MEOS pathway, increasing the rate of alcohol metabolism but also the production of harmful ROS.

Effects of Alcohol Metabolism

• Acute Effects:
  • Central nervous system depression, leading to impaired coordination, judgment, and reaction times.
  • Increased production of acetaldehyde, which can cause hangover symptoms such as headache, nausea, and vomiting.
• Chronic Effects:
  • Liver damage, including fatty liver, hepatitis, fibrosis, and cirrhosis.
  • Increased risk of certain cancers, particularly of the liver, oesophagus, mouth, and throat.
  • Cardiovascular problems, including hypertension and cardiomyopathy.
  • Neurological issues, such as neuropathy and cognitive impairments.
• Alcohol Tolerance and Dependence:
  • Regular consumption can lead to tolerance, requiring higher amounts of alcohol to achieve the same effects.
  • Dependence and addiction can develop, characterized by cravings and withdrawal symptoms when not drinking.

Diagnosis and Treatment

• Diagnosis:
  • Blood alcohol concentration (BAC) tests measure the amount of alcohol in the bloodstream.
  • Liver function tests (LFTs) assess liver damage and function.
  • Screening tools like the AUDIT (Alcohol Use Disorders Identification Test) identify problematic drinking behaviors.
• Treatment:
  • Behavioral Therapies: Cognitive-behavioral therapy (CBT), motivational interviewing, and support groups like Alcoholics Anonymous (AA).
  • Medications: Disulfiram (Antabuse) discourages drinking by causing unpleasant reactions to alcohol, naltrexone reduces cravings, and acamprosate helps maintain abstinence.
  • Lifestyle Changes: Healthy diet, regular exercise, and avoiding triggers that lead to drinking.
  • Medical Interventions: In severe cases, detoxification and treatment in specialized rehabilitation centres.

Summary

Alcohol metabolism involves enzymatic pathways primarily in the liver, converting ethanol to acetaldehyde and then to acetate. Factors such as genetics, gender, age, and chronic alcohol consumption affect the rate of metabolism. Understanding the pathways and effects of alcohol metabolism is crucial for addressing the health implications of alcohol consumption and for providing effective diagnosis and treatment of alcohol-related disorders.