Dirty Biochemistry Series: Alcohol Metabolism

Overview

• Alcohol metabolism consists of a short biochemical pathway with only two steps.
• Key focus: Cofactors involved in the pathway, which are high-yield for exams.

Alcohol Metabolism Pathway

1. Ethanol to Acetaldehyde

   • Enzyme: Alcohol dehydrogenase (also known as ethanol dehydrogenase)
   • Location: Occurs in the cytosol

2. Acetaldehyde to Acetate

   • Enzyme: Acetaldehyde dehydrogenase
   • Location: Occurs in the mitochondria

Important Concepts

• Zero Order Kinetics:
  • Alcohol metabolism (ethanol to acetaldehyde) follows zero order kinetics.
  • Constant amount of alcohol is eliminated at a constant rate, regardless of intake.

High-Yield Cofactor

• NAD+ to NADH Conversion:
  • Occurs during ethanol conversion to acetaldehyde.
  • Leads to increased NADH and decreased NAD+ levels.

Effects of Increased NADH/NAD+ Ratio

• Decreased Gluconeogenesis:

  • Leads to fasting hypoglycemia due to impaired glucose maintenance.

• Decreased TCA Cycle Activity:

  • Acetyl-CoA cannot enter TCA cycle, leading to ketosis (acetyl-CoA diverted to ketone production).

• Lactic Acidosis:

  • Increased conversion of pyruvate to lactate to utilize excess NADH.

Mnemonic

• Natty Light:
  • Help remember increased NADH/NAD+ ratio.
  • Association: "Natty Light" is a cheap beer, relates to alcohol metabolism.

Enzyme Inhibitors

• Fomepizole:

  • Inhibits alcohol dehydrogenase.
  • Used to treat methanol and ethylene glycol poisoning.
  • Mnemonic: "Fomepizole MEP" (Methanol, Ethylene glycol, Poisoning)

• Disulfiram:

  • Inhibits acetaldehyde dehydrogenase.
  • Causes acetaldehyde buildup, leading to hangover symptoms.
  • Used in treating alcohol use disorder to deter drinking.

Additional Notes

• Further details on how the NADH/NAD+ ratio affects other pathways can be found in other lectures of the series.
• Future lessons will cover more on alcohol-related topics.