PARACETAMOL PHARMACOKINETICS PATHWAY (PW:0001525)

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Description

Paracetamol or N-acetyl-p-aminophenol (APAP), also known as acetaminophen or by its trade in the USA as Tylenol, is a widely used analgesic and antipyretic drug. However, overdose of paracetamol - accidental or intentional - is associated with hepatotoxicity and a leading cause of liver failure. APAP metabolism occurs in the liver where it is primarily subject to glucuronidation and sulfation by members of phase II biotransformation enzymes. To a lesser extent, it is also metabolized by members

Pathway Diagram:

Elsevier Inc. paracetamol sulfate ---> biliary excretion paracetamol glucuronide ---> biliary excretion Abcc2 APAP-GSH ---> biliary excretion paracetamol sulfate ---> basolateral excretion paracetamol glucuronide ---> basolateral excretion glutathione Abcc4 Abcc3 Abcg2 paracetamol ---> paracetamol glucuronide paracetamol ---> paracetamol sulfate Napqi ---> APAP-GSH biliary excretion basolateral excretion glutathione ---- Napqi paracetamol ---> Napqi Cyp2e1 paracetamol sulfate paracetamol paracetamol glucuronide APAP-GSH Napqi UGT1A1 UGT1A6 SULT1A1 SULT1A3 SULT1A4 SULT1E1
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Genes in Pathway:

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paracetamol pharmacokinetics pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Abcb1a ATP binding cassette subfamily B member 1A JBrowse link 4 22,339,829 22,517,642 RGD:10402751
G Abcc1 ATP binding cassette subfamily C member 1 JBrowse link 10 549,537 672,235 RGD:10402751
G Abcc2 ATP binding cassette subfamily C member 2 JBrowse link 1 263,554,426 263,612,556 RGD:8552693
G Abcc3 ATP binding cassette subfamily C member 3 JBrowse link 10 82,047,308 82,116,928 RGD:8552693
G Abcc4 ATP binding cassette subfamily C member 4 JBrowse link 15 103,695,415 103,927,980 RGD:8552693
RGD:10402751
G Abcc5 ATP binding cassette subfamily C member 5 JBrowse link 11 84,395,982 84,490,215 RGD:10402751
G Abcg2 ATP binding cassette subfamily G member 2 JBrowse link 4 88,765,441 88,890,268 RGD:8552693
RGD:10402751
G Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 JBrowse link 8 62,451,360 62,458,244 RGD:10402751
G Cyp2d4 cytochrome P450, family 2, subfamily d, polypeptide 4 JBrowse link 7 123,599,264 123,608,436 RGD:10402751
G Cyp2e1 cytochrome P450, family 2, subfamily e, polypeptide 1 JBrowse link 1 213,511,892 213,522,195 RGD:8552693
RGD:10402751
G Dnajb11 DnaJ heat shock protein family (Hsp40) member B11 JBrowse link 11 81,741,342 81,757,806 RGD:10402751
G Erp29 endoplasmic reticulum protein 29 JBrowse link 12 40,619,377 40,625,884 RGD:10402751
G Gstp1 glutathione S-transferase pi 1 JBrowse link 1 219,291,679 219,294,147 RGD:10402751
G Gstt1 glutathione S-transferase theta 1 JBrowse link 20 13,799,102 13,816,527 RGD:10402751
G Hsp90b1 heat shock protein 90 beta family member 1 JBrowse link 7 27,226,570 27,240,533 RGD:10402751
G Hspa5 heat shock protein family A member 5 JBrowse link 3 13,838,304 13,842,763 RGD:10402751
G Hyou1 hypoxia up-regulated 1 JBrowse link 8 48,699,796 48,711,912 RGD:10402751
G Pdia2 protein disulfide isomerase family A, member 2 RGD:10402751
G Pdia4 protein disulfide isomerase family A, member 4 JBrowse link 4 77,470,636 77,489,535 RGD:10402751
G Pdia6 protein disulfide isomerase family A, member 6 JBrowse link 6 42,568,269 42,585,654 RGD:10402751
G Ppib peptidylprolyl isomerase B JBrowse link 8 71,719,681 71,725,538 RGD:10402751
G Sdf2l1 stromal cell-derived factor 2-like 1 JBrowse link 11 88,122,271 88,124,513 RGD:10402751
G Sult1a1 sulfotransferase family 1A member 1 JBrowse link 1 198,100,586 198,104,106 RGD:10402751
G Sult1e1 sulfotransferase family 1E member 1 JBrowse link 14 22,070,861 22,089,264 RGD:8552693
RGD:10402751
G Sult2a1 sulfotransferase family 2A member 1 JBrowse link 1 76,558,721 76,614,315 RGD:10402751
G Ugt1a1 UDP glucuronosyltransferase family 1 member A1 JBrowse link 9 95,295,701 95,302,822 RGD:8552693
RGD:10402751
G Ugt1a6 UDP glucuronosyltransferase family 1 member A6 JBrowse link 9 95,241,609 95,302,822 RGD:8552693
RGD:10402751
G Ugt1a9 UDP glucuronosyltransferase family 1 member A9 JBrowse link 9 95,161,157 95,302,822 RGD:10402751

Pathway Gene Annotations

Disease Annotations Associated with Genes in the paracetamol pharmacokinetics pathway
Disease TermsGene Symbols
Colitis, UlcerativeAbcb1a
Pathway Annotations Associated with Genes in the paracetamol pharmacokinetics pathway
Pathway TermsGene Symbols
acetylsalicylic acid pharmacodynamics pathwayCyp2e1
antigen processing and presentation pathwayHspa5
antipyrine drug pathwayCyp2e1
arachidonic acid metabolic pathwayCyp2e1
artemether pharmacokinetics pathwayUgt1a9
ascorbate and aldarate metabolic pathwayUgt1a1 , Ugt1a6 , Ugt1a9
azathioprine pharmacodynamics pathwayAbcc4 , Abcc5
bile acid transport pathwayAbcb1a , Abcc2 , Abcc3 , Abcc4 , Abcg2 , Sult2a1
caffeine metabolic pathwayCyp1a2
caffeine pharmacokinetics pathwayCyp1a2 , Cyp2e1
celecoxib pharmacodynamics pathwayCyp2d4 , Cyp2e1
celecoxib pharmacokinetics pathwayCyp2d4
citalopram pharmacodynamics pathwayCyp2d4
citalopram pharmacokinetics pathwayCyp2d4
clomipramine pharmacokinetics pathwayCyp1a2 , Cyp2d4
clopidogrel pharmacodynamics pathwayAbcb1a , Cyp1a2
clopidogrel pharmacokinetics pathwayAbcb1a , Cyp1a2
codeine and morphine pharmacodynamics pathwayCyp2d4 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1
codeine and morphine pharmacokinetics pathwayCyp2d4 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1
desipramine pharmacodynamics pathwayCyp2d4
desipramine pharmacokinetics pathwayCyp2d4
diclofenac pharmacodynamics pathwayCyp2e1
diflunisal pharmacodynamics pathwayCyp2e1
disulfiram pharmacodynamics pathwayCyp2e1
docetaxel pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcg2
doxepin pharmacokinetics pathwayCyp1a2 , Cyp2d4
doxorubicin pharmacokinetics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3 , Abcg2
Endoplasmic Reticulum-associated degradation pathwayDnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia4 , Pdia6
erlotinib pharmacodynamics pathwayAbcb1a , Abcg2
estradiol biosynthetic pathwaySult1e1 , Sult2a1
etodolac pharmacodynamics pathwayCyp2e1
etoposide pharmacodynamics pathwayAbcb1a , Abcc3 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1
etoposide pharmacokinetics pathwayAbcb1a , Abcc3 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1
felbamate pharmacokinetics pathwayCyp2e1
fenoprofen pharmacodynamics pathwayCyp2e1
fluoxetine pharmacodynamics pathwayCyp2d4
fluoxetine pharmacokinetics pathwayCyp2d4
flurbiprofen pharmacodynamics pathwayCyp2e1
glutathione conjugation pathwayGstp1 , Gstt1
glutathione metabolic pathwayGstp1 , Gstt1
hypoxia inducible factor pathwayAbcb1a , Abcg2
ibuprofen pharmacodynamics pathwayCyp2e1 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a9
ibuprofen pharmacokinetics pathwayDnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a9
imipramine pharmacodynamics pathwayCyp1a2 , Cyp2d4
imipramine pharmacokinetics pathwayCyp1a2 , Cyp2d4
indometacin pharmacodynamics pathwayCyp2e1
indometacin pharmacodynamics pathwayCyp2e1
interleukin-6 signaling pathwayHsp90b1
irinotecan pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcg2 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a9
irinotecan pharmacokinetics pathwayAbcb1a , Abcc1 , Abcc2 , Abcg2 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a9
ketoprofen pharmacodynamics pathwayCyp2e1
ketorolac pharmacodynamics pathwayCyp2e1
lamivudine pharmacokinetics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3 , Abcc4 , Abcg2 , Sult1a1
leukotriene C4 synthase deficiency pathwayCyp2e1
lidocaine pharmacodynamics pathwayCyp1a2
lidocaine pharmacokinetics pathwayCyp1a2
linoleic acid metabolic pathwayCyp1a2 , Cyp2e1
lornoxicam pharmacodynamics pathwayCyp2e1
magnesium salicylate pharmacodynamics pathwayCyp2e1
mefenamic acid pharmacodynamics pathwayCyp2e1
meloxicam pharmacodynamics pathwayCyp2e1
mercaptopurine pharmacodynamics pathwayAbcc4 , Abcc5
mercaptopurine pharmacokinetics pathwayAbcc4 , Abcc5
methadone pharmacodynamics pathwayCyp2d4
methadone pharmacokinetics pathwayCyp2d4
multidrug resistance-associated protein mediated transport pathwayAbcc1 , Abcc2 , Abcc3 , Abcc4 , Abcc5
mycophenolic acid pharmacokinetics pathwayAbcb1a , Abcc2 , Abcg2 , Ugt1a9
nabumetone pharmacodynamics pathwayCyp2e1
naproxen pharmacodynamics pathwayCyp2e1
neviparine pharmacokinetics pathwayCyp2d4
nicotine pharmacodynamics pathwayUgt1a9
nicotine pharmacokinetics pathwayUgt1a9
NOD-like receptor signaling pathwayHsp90b1
O-linked glycan biosynthetic pathwayUgt1a1 , Ugt1a6 , Ugt1a9
paracetamol drug pathwayCyp2e1
paracetamol pharmacokinetics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3 , Abcc4 , Abcc5 , Abcg2 , Cyp1a2 , Cyp2d4 , Cyp2e1 , Dnajb11 , Erp29 , Gstp1 , Gstt1 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Sult1a1 , Sult1e1 , Sult2a1 , Ugt1a1 , Ugt1a6 , Ugt1a9
paracetamol response pathwayCyp2e1
pentose and glucuronate interconversion pathwayUgt1a1 , Ugt1a6 , Ugt1a9
phase I biotransformation pathway via cytochrome P450Cyp1a2 , Cyp2d4 , Cyp2e1 , Gstp1 , Gstt1 , Ugt1a1 , Ugt1a6 , Ugt1a9
phenytoin pharmacodynamics pathwayCyp1a2 , Cyp2e1 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a6 , Ugt1a9
piroxicam pharmacodynamics pathwayCyp2e1
porphyrin and chlorophyll metabolic pathwayUgt1a1 , Ugt1a6 , Ugt1a9
prion diseases pathwayHspa5
prostate cancer pathwayGstp1 , Hsp90b1
retinol metabolic pathwayCyp1a2 , Dnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a6 , Ugt1a9
salicylic acid pharmacodynamics pathwayCyp2e1
sodium salicylate pharmacodynamics pathwayCyp2e1
sorafenib pharmacokinetics pathwayDnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1 , Ugt1a9
sphingosine 1-phosphate signaling pathwayAbcc1
starch and sucrose metabolic pathwayUgt1a1 , Ugt1a6 , Ugt1a9
steroid hormone biosynthetic pathwaySult1e1 , Ugt1a1 , Ugt1a6 , Ugt1a9
sulfite oxidase deficiency pathwaySult1a1 , Sult1e1
sulfur metabolic pathwaySult1a1 , Sult1e1
sulindac pharmacodynamics pathwayCyp2e1
syndecan signaling pathwayPpib
tamoxifen pharmacodynamics pathwayCyp2d4 , Sult1a1
tamoxifen pharmacokinetics pathwayCyp2d4 , Sult1a1 , Sult2a1
tenoxicam pharmacodynamics pathwayCyp2e1
testosterone biosynthetic pathwaySult2a1
tiaprofenic acid pharmacodynamics pathwayCyp2e1
tioguanine pharmacodynamics pathwayAbcc4 , Abcc5
tolmetin pharmacodynamics pathwayCyp2e1
tramadol pharmacokinetics pathwayAbcc2 , Cyp2d4
tryptophan metabolic pathwayCyp1a2
tyrosinemia type III disease pathwayAbcb1a , Abcc1 , Abcc2 , Abcg2
valdecoxib pharmacodynamics pathwayCyp2e1
venlafaxine pharmacokinetics pathwayAbcb1a , Cyp2d4
vinblastine pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3
vincristine pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3
vindesine pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3
vinorelbine pharmacodynamics pathwayAbcb1a , Abcc1 , Abcc2 , Abcc3
vitamin A deficiency pathwayDnajb11 , Erp29 , Hsp90b1 , Hspa5 , Hyou1 , Pdia2 , Pdia4 , Pdia6 , Ppib , Sdf2l1 , Ugt1a1
Phenotype Annotations Associated with Genes in the paracetamol pharmacokinetics pathway

References Associated with the paracetamol pharmacokinetics pathway:

Ontology Path Diagram:

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