Lecture Notes: Alcohol Metabolism

Overview

• Focus on alcohol metabolism in the context of biochemistry.
• Alcohol metabolism consists of two main steps.
• Key emphasis on cofactors involved in this pathway, which are often a source of exam questions.

Key Steps in Alcohol Metabolism

1. Ethanol to Acetaldehyde

   • Enzyme: Alcohol Dehydrogenase (also referred to as Ethanol Dehydrogenase)
   • Location: Cytosol

2. Acetaldehyde to Acetate

   • Enzyme: Acetaldehyde Dehydrogenase
   • Location: Mitochondria

Alcohol Dehydrogenase Kinetics

• Alcohol metabolism follows zero-order kinetics:
  • A constant amount of ethanol is metabolized over time, regardless of concentration.
  • Example: One beer or twenty does not change the rate of metabolism.

Important Cofactors

• NAD+ is crucial in the first step:
  • Conversion of ethanol to acetaldehyde also converts NAD+ to NADH.
  • Leads to an increased NADH/NAD+ ratio in the body during excessive alcohol consumption.

Clinical Implications of Increased NADH/NAD+ Ratio

1. Decreased Gluconeogenesis

   • Results in fasting hypoglycemia due to insufficient glucose production.

2. Decreased TCA Cycle Activity

   • Excess acetyl-CoA, which cannot enter TCA, is diverted to ketone production, leading to ketosis.

3. Increased Lactic Acidosis

   • Elevated lactate levels due to pyruvate being converted to lactate, consuming NADH to correct the NADH/NAD+ imbalance.

Mnemonic for NADH/NAD+ Ratio

• NADY Light: Connects the concept of the NADH/NAD+ ratio to alcohol metabolism through the popular beer.

Drug Interactions with Alcohol Metabolism

• Femepazole:

  • Inhibits alcohol dehydrogenase.
  • Used as an antidote for methanol and ethylene glycol poisoning.
  • Remember: MEP (Methanol, Ethylene Glycol, Poisoning).

• Disulfiram:

  • Inhibits acetaldehyde dehydrogenase.
  • Causes accumulation of acetaldehyde, leading to hangover-like symptoms to discourage drinking.

Conclusion

• Summarized the pathway and its clinical implications.
• Encouraged review of prior lessons for deeper understanding of related biochemical processes.