Pathway Human Homo sapiens

Paracetamol ADME

R-HSA-9753281 in Reactome release 97: under Drug ADME, with 29 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9753281 (mouse), R-RNO-9753281 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9753281.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2021-12-08
Events inside: 13, counted from the record
Also named: Acetaminophen ADME; APAP ADME

Paracetamol (APAP, aka acetaminophen or N-acetyl-p-aminophenol) is an analgesic drug used for to treat mild to moderate pain and as an antipyretic agent. It is one of the most widely used drugs in the world and is available alone or in combination with other drugs for pain relief, fever and allergy. It is thought to act through the inhibition of cyclooxygenases 1 and 2 (Graham et al. 2013, Esh et al. 2021). Paracetamol is generally safe at therapeutic doses but in overdose cases, it causes mitochondrial dysfunction and centrilobular necrosis in the liver which can lead to death.

APAP has a high oral bioavailability (~88%), is well absorbed and reaches peak blood concentrations after 90 minutes after ingestion. APAP binds plasma proteins to a small extent and has a plasma half-life of 1.5-3 hours. Most of the drug is eliminated by glucuronidate and sulfate conjugation (~55% and ~30% respectively) in the liver or as unchanged drug (~5%) (Forrest et al. 1982). A small amount (5-15%) is oxidised to the reactive metabolite N-acetyl-para-benzoquinone imine (NAPQI). NAPQI is usually detoxified by binding to liver glutathione but in overdose cases, glutathione is depleted and NAPQI instead, binds to sulfhydryl groups on proteins, leading to liver damage. ABCC2, ABCC3, ABCC4 and ABCG2 transporters mediate the efflux of APAP metabolites out of cells (McGill & Jaeschke 2013).

Literature Reactome attaches

Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosisPharm Res, 2013, vol. 30, p. 2174-87PubMed 23462933
Clinical pharmacokinetics of paracetamolClin Pharmacokinet, 1982, vol. 7, p. 93-107PubMed 7039926
The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findingsInflammopharmacology, 2013, vol. 21, p. 201-32PubMed 23719833
Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?Pharmacol Res Perspect, 2021, vol. 9, p. e00835PubMed 34278737

Reactome's record lists 14 orthologous events, R-RNO-9753281 (Rattus norvegicus), R-MMU-9753281 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Paracetamol ADME". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9753281 with StableID: R-HSA-9753281.3 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 29 genes in this human pathway; showing 1 to 29, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneABCC1	AuthorityHGNC:51	Mapping file id4363 NCBI file	EvidenceTAS
GeneABCC2	AuthorityHGNC:53	Mapping file id1244 NCBI file	EvidenceTAS
GeneABCC3	AuthorityHGNC:54	Mapping file id8714 NCBI file	EvidenceTAS
GeneABCC4	AuthorityHGNC:55	Mapping file id10257 NCBI file	EvidenceTAS
GeneABCC5	AuthorityHGNC:56	Mapping file id10057 NCBI file	EvidenceTAS
GeneABCG2	AuthorityHGNC:74	Mapping file id9429 NCBI file	EvidenceTAS
GeneACY1	AuthorityHGNC:177	Mapping file id95 NCBI file	EvidenceTAS
GeneCNDP2	AuthorityHGNC:24437	Mapping file id55748 NCBI file	EvidenceTAS
GeneCYP2E1	AuthorityHGNC:2631	Mapping file id1571 NCBI file	EvidenceTAS
GeneGGT1	AuthorityHGNC:4250	Mapping file id2678 NCBI file	EvidenceTAS
GeneGGT5	AuthorityHGNC:4260	Mapping file id2687 NCBI file	EvidenceTAS
GeneGGT6	AuthorityHGNC:26891	Mapping file id124975 NCBI file	EvidenceTAS
GeneGGT7	AuthorityHGNC:4259	Mapping file id2686 NCBI file	EvidenceTAS
GeneGSTM1	AuthorityHGNC:4632	Mapping file id2944 NCBI file	EvidenceTAS
GeneGSTP1	AuthorityHGNC:4638	Mapping file id2950 NCBI file	EvidenceTAS
GeneGSTT1	AuthorityHGNC:4641	Mapping file id2952 NCBI file	EvidenceTAS
GeneNAT1	AuthorityHGNC:7645	Mapping file id9 NCBI file	EvidenceTAS
GeneNAT2	AuthorityHGNC:7646	Mapping file id10 NCBI file	EvidenceTAS
GeneSULT1A1	AuthorityHGNC:11453	Mapping file id6817 NCBI file	EvidenceTAS
GeneSULT1A3	AuthorityHGNC:11455	Mapping file id6818 NCBI file	EvidenceTAS
GeneSULT1A4	AuthorityHGNC:30004	Mapping file id445329 NCBI file	EvidenceTAS
GeneSULT1C4	AuthorityHGNC:11457	Mapping file id27233 NCBI file	EvidenceTAS
GeneSULT1E1	AuthorityHGNC:11377	Mapping file id6783 NCBI file	EvidenceTAS
GeneSULT2A1	AuthorityHGNC:11458	Mapping file id6822 NCBI file	EvidenceTAS
GeneUGT1A1	AuthorityHGNC:12530	Mapping file id54658 NCBI file	EvidenceTAS
GeneUGT1A10	AuthorityHGNC:12531	Mapping file id54575 NCBI file	EvidenceTAS
GeneUGT1A6	AuthorityHGNC:12538	Mapping file id54578 NCBI file	EvidenceTAS
GeneUGT1A9	AuthorityHGNC:12541	Mapping file id54600 NCBI file	EvidenceTAS
GeneUGT2B15	AuthorityHGNC:12546	Mapping file id7366 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Drug ADMER-HSA-9748784109 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.