What is the role of ethanol metabolism in alcoholic ketoacidosis (AKA)?

Updated: Aug 27, 2020
  • Author: George Ansstas, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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The metabolism of alcohol itself is a probable contributor to the ketotic state. Alcohol dehydrogenase (ADH), a cytosolic enzyme, metabolizes alcohol to acetaldehyde in hepatocytes. Acetaldehyde is metabolized further to acetic acid by aldehyde dehydrogenase. This reaction takes place within the mitochondria. Both steps require the reduction of nicotinamide adenine dinucleotide (NAD+) to reduced nicotinamide adenine dinucleotide (NADH). Thus, NAD+ is consumed and NADH is generated.

The resulting increase in the NADH/NAD+ ratio inhibits hepatic gluconeogenesis and elevates the ratio of hydroxybutyric acid to acetoacetic acid. Acetic acid (an acyl group carrier) is linked with coenzyme A (a thiol) to produce Acetyl-CoA. This process is catalyzed by the enzyme acetyl-CoA synthetase.

The decreased ratio of NAD+ to NADH has the following implications:

  • Impaired conversion of lactate to pyruvate with an increase in serum lactic acid levels

  • Impaired gluconeogenesis because pyruvate is not available as a substrate for glucose production

  • A shift in the hydroxybutyrate (β-OH) to acetoacetate (AcAc) equilibrium toward β-OH

In contrast to diabetic ketoacidosis, the predominant ketone body in AKA is β-OH. Routine clinical assays for ketonemia test for AcAc and acetone but not for β-OH. Clinicians underestimate the degree of ketonemia if they rely solely on the results of laboratory testing.

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