NAPQI binds proteins in hepatocytes

Stable Identifier
R-HSA-9753916
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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NAPQI binds proteins in hepatocytes
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After a toxic dose of paracetamol (APAP), the normal sulfation and glucuronidation pathways get saturated and higher proportions of the drug get oxidized to N-acetyl-p-benzoquinine imine (NAPQI). Higher levels of NAPQI eventually deplete the protective glutathione stores and start to form protein adducts by binding to cysteine groups on cellular proteins (James et al. 2009). NAPQI primarily targets mitochondrial proteins and ion channels leading to the loss of energy production, ion misbalance and cell death, eventually leading to hepatotoxicity (reviews - James et al. 2003, Hodgman & Garrard 2012)
Literature References
PubMed ID Title Journal Year
19439490 Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure

Simpson, PM, Davern, TJ, James, LP, Lee, WM, Capparelli, E, Hinson, JA, Roberts, DW, Letzig, L

Drug Metab Dispos 2009
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Authored
Jassal, B  (2021-09-20)
Reviewed
Huddart, R  (2021-10-13)
Created
Jassal, B  (2021-09-20)
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