Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH.
Synthetic N-acetyl-p-benzoquinone imine reacted with reduced glutathione (GSH), [14C]acetaminophen, and NADPH. It reacted rapidly with GSH to yield acetaminophen (33%) and 3-(glutathion-S-yl)acetaminophen (67%), and with acetaminophen or NADPH to yield acetaminophen polymers. The data suggested that N-acetyl-p-benzoquinone imine was reduced by GSH to form acetaminophen but primarily reacted with GSH to form 3-(glutathion-S-yl)acetaminophen. The evidence further suggested that N-acetyl-p-benzoquinone imine comproportionated with [14C]acetaminophen to yield a mixture of radioactive and nonradioactive N-acetyl-p-benzosemiquinone imine which subsequently formed acetaminophen polymers by a radical coupling reaction. [14C]Acetaminophen was incorporated into the acetaminophen polymers. The amount of 14C incorporation was dependent on the initial concentration of [14C]acetaminophen and N-acetyl-p-benzoquinone imine. An increase in the ratio of [14C]acetaminophen to N-acetyl-p-benzoquinone imine resulted in an increase in [14C] acetaminophen incorporation into the acetaminophen polymers. NADPH reduced N-acetyl-p-benzoquinone imine to acetaminophen and acetaminophen polymers were formed. When [14C]N-acetyl-p-benzoquinone imine was incubated without acetaminophen, only minor amounts of acetaminophen polymerization were observed.
D000082:Acetaminophen / Q000378:metabolism*; D016227:Benzoquinones; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005978:Glutathione / Q000378:metabolism*; D007097:Imines / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D011108:Polymers
D016227:Benzoquinones; D007097:Imines; D011108:Polymers; D000082:Acetaminophen; D009249:NADP; C028473:N-acetyl-4-benzoquinoneimine; D005978:Glutathione