Updated: 12/4/2018

Ethanol Metabolism

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Evidence
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Topic
  • Overview
    • Function
      • elimate ethanol (EtOH)
        • CNS depressant/toxin
    • Kinetics
      • NAD+ is limiting reagent
      • alcohol dehydrogenase operates via zero-order kinetics
      • inhibitors
        • fomepizole inhibits alcohol dehydrogenase
          • antidote for suspected ethylene glycol or methanol poisoning
        • disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase
          • acetaldehyde accumulates
          • leads to hangover symptoms
          • prescribed to help recovering alcoholics
    • Clinical relevance
      • ethanol hypoglycemia
        • pathophysiology
          • ↑ in EtOH metabolism → ↑ NADH/NAD+ ratio
          • NADH/NAD+ ratio changes energy generating kinetics
          • lactate favored over pyruvate
            • lactate + NAD+ → pyruvate + NADH
            • no free NAD+ for required conversion
          • glycerol-3-phosphate favored over DHAP
            • G3P + NAD+ → DHAP + NADH
          • malate favored over oxaloacetate
            • malate + NAD+ → OAA + NADH
        • presentation
          • lactic acidosis
            • ↑ lactate
          • fatty liver
            • ↑ G3P results in ↑ synthesis of TGs
      • ethanol + extreme physical exertion
        • severe hypoglycemia
        • EtOH inhibits the Cori cycle by consumption of free NAD+
          • conversion of lactate to glucose in anaerobic metabolism
          • lactic acidosis

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(M1.BC.14.1) An 18-year-old male presents to the emergency room smelling quite heavily of alcohol and is unconscious. A blood test reveals severe hypoglycemic and ketoacidemia. A previous medical history states that he does not have diabetes. The metabolism of ethanol in this patient's hepatocytes resulted in an increase of the [NADH]/[NAD+] ratio. Which of the following reaction is favored under this condition?

QID: 106289

Pyruvate to acetyl-CoA

13%

(28/210)

Citrate to isocitrate

1%

(3/210)

Oxaloacetate to malate

63%

(132/210)

Oxaloacetate to phosphoenolpyruvate

19%

(40/210)

Fumarate to malate

1%

(3/210)

M 1 E

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