CLINICAL CASES
373
[40.2]
C. N-acetyl benzoquinoneimine is toxic, whereas acetaminophen glu-
curonide, acetaminophen sulfate, and acetaminophen glutathionate
are nontoxic acetaminophen conjugates. N-acetyl-p-aminophenol is
another name for acetaminophen.
[40.3]
C. Glutathione (y-glutamylcysteinylglycine) is a tripeptide of glu-
tamic acid, cysteine, and glycine in which the amino terminal gluta-
mate residue is in a peptide linkage through its side-chain carboxyl
group to the cysteine residue.
B IO C H E M IS T R Y PE A R L S
The major pathway of removal of acetaminophen is by formation of
a glucuronide conjugate.
Acetaminophen is oxidized by the cytochrome P450 system, yield-
ing the deleterious product A-acetyl benzoquinoneimine, an
unstable intermediate that can react with cellular macromolecules
and thus damage them.
The liver has a high concentration of cytochrome P450 and is par-
ticularly susceptible to acetaminophen toxicity.
A-acetylcysteine is the antidote to acetaminophen toxicity and facil-
itates glutathione synthesis by increasing the concentrations of
one of the reactants of the first synthetic step.
REFERENCE
Goodman AG, Gilman LS, eds. The Pharmological Basis of Therapeutics, 10th ed.
New York: Mc-graw-Hill, 2001.
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