Pathway maps

Acetaminophen metabolism
Acetaminophen metabolism

Object List (links open in MetaCore):

GSTP1, CYP2D6, UGT2B15, (Acetylamino-2-hydroxyphenyl)- glutathione, CYP2A13, CYP1A2, UGT1A3, 3-Hydroxy- acetaminophen, NQO1, Acetaminophen O-glucuronide,, N-Acetyl-1,4-benzoquinone imine, CYP2E1, Acetaminophen, CYP2A6, CYP3A4, UGT1A6,,, UGT1A10, CYP2B1 Rat, SULT1A1,, CYP1A1,,, UGT1A9, Acetaminophen sulfate, UGT1A1


Acetaminophen metabolism

Acetaminophen is a widely used analgesic and antipyretic agent considered safe at therapeutic doses. However, it can cause acute hepatic centrilobular necrosis in both humans and experimental animals when consumed in large doses.

Acetaminophen is bioactivated by the enzymes Cytochrome P450, family 1, subfamily A, polypeptide 1 ( CYP1A1 ) [1], Cytochrome P450, family 1, subfamily A, polypeptide 2 ( CYP1A2) [2] [3], Cytochrome P450, family 2, subfamily A, polypeptide 6 ( CYP2A6 ) [4], [5], [3], Cytochrome P450, family 2, subfamily b, polypeptide 1 ( CYP2B1 ) rat [1], Cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1 ) [4], [6], [3], [7], [8], Cytochrome P450, family 3, subfamily A, polypeptide 4 ( CYP3A4 ) [3], Cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) [5], and cytochrome P450, family 2, subfamily A, polypeptide 13 ( CYP2A13 ) [9]. It is oxidized via two pathways to form a toxic intermediate N-acetyl-1,4-benzoquinone imine believed to be responsible for the hepatotoxicity of Acetaminophen, and a nontoxic catechol metabolite 3-Hydroxy-acetaminophen.

At normal Acetaminophen dosing, N-acetyl-1,4-benzoquinone imine is rapidly detoxified by Glutathione S-transferase pi 1 ( GSTP1 ) to nontoxic metabolite (Acetylamino-2-hydroxyphenyl)-glutathione. Additionally, N-acetyl-1,4-benzoquinone imine can be enzymatically reduced back to Acetaminophen by NAD(P)H dehydrogenase, quinone 1 ( NQO1 ) [10], [11].

Acetaminophen can also be metabolized via an alternative pathway that involves its sulfation by sulfotransferases, such as Sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 ( SULT1A1 ) [12], [13], [14] ) or glucuronidation by UDP-glucuronosyltransferases, such as UDP glucuronosyltransferase 1 family, polypeptide A1 ( UGT1A1 ) [15], [16], [17], UDP glucuronosyltransferase 1 family, polypeptide A10 ( UGT1A10 ) [15], UDP glucuronosyltransferase 1 family, polypeptide A3 ( UGT1A3 ) [18], UDP glucuronosyltransferase 1 family, polypeptide A6 ( UGT1A6 ) [16], [15], [17], UDP glucuronosyltransferase 1 family, polypeptide A9 ( UGT1A9 ) [15], [16], [19], [17], or UDP glucuronosyltransferase 2 family, polypeptide B15 ( UGT2B15 ) [17], [16].


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