APAP hepatotoxicity does not originate from the molecule itself but is rather attributed to one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI). This metabolic intermediate forms upon oxidation of APAP via CYP2E1 enzyme. Normally, NAPQI is quickly conjugated with glutathione (GSH) via glutathione transferase to produce the non-toxic compound APAP-GSH. However, a rapid influx of NAPQI depletes GSH stores, causing NAPQI to build up in liver cells (15). For this reason, patients who overdose on APAP are treated with N-Acetyl Cysteine (NAC), which stimulates GSH production to protect against liver damage (16).
To see a full scheme of the APAP metabolism and to learn about its interaction with ethanol, click here.
November 7, 2016 at 7:56 pm
I love the bar graph, since I think it does a really good job of showing the relationship between NAPQI and GSH.
I think it could be beneficial to show a figure which shows the pathways you describe on this slide. Can you show the conjugation of NAPQI and GSH to produce APAP-GSH? Also I know yo explain N-acetyl cysteine later, so maybe include a hyperlink to that page? When I first read it, I was left wanting to know more about this antidotal process.
November 10, 2016 at 5:48 pm
Delia, I think the pathways are described/shown in more detail on their “interactions with ethanol” subpage.
Maybe when you include the hyperlink to the N-acetyl cysteine page you can also include a hyperlink to the interactions with ethanol page.