Metabolism of N-acetyl-L-cysteine. Some structural requirements for the deacetylation and consequences for the oral bioavailability

Biochem Pharmacol. 1989 Nov 15;38(22):3981-5. doi: 10.1016/0006-2952(89)90677-1.


Rat liver, lung and intestine homogenates deacetylated N-acetyl-L-cysteine. Nearly stoichiometric amounts of L-cysteine were recovered. In rat liver, the enzyme activity was associated with the cytosolic fraction. Liver cytosol was much less active. N-Acetyl-D-cysteine or the disulphide of N-acetyl-L-cysteine were not deacetylated or in other ways consumed in vitro. Isolated, perfused rat liver did not retain or metabolize N-acetyl-L-cysteine to any measurable extent during single-pass experiments. N-Acetyl-L-cysteine or N-acetyl-D-cysteine were injected into a ligated segment of rat intestine in situ. After 1 hr 2% of the L-isomer and 35% of the D-isomer remained in the intestinal lumen. Systemic plasma levels were less than 3 microM of the L-form and congruent to 40 microM of the D-form. We conclude that deacetylation in the intestinal mucosa and possibly in the intestinal lumen is the major factor determining the low oral bioavailability of N-acetyl-L-cysteine. The deacetylation is discussed on the basis of the subcellular localization and the structural requirement of the reaction.

Publication types

  • Comparative Study

MeSH terms

  • Acetylation
  • Acetylcysteine / administration & dosage
  • Acetylcysteine / metabolism*
  • Acetylcysteine / pharmacokinetics
  • Animals
  • Biological Availability
  • Cytosol / metabolism
  • Dogs
  • Female
  • Humans
  • Hydrolysis
  • Intestinal Mucosa / metabolism*
  • Kinetics
  • Liver / metabolism*
  • Lung / metabolism*
  • Male
  • Mice
  • Rats
  • Rats, Inbred Strains


  • Acetylcysteine