Reactome | SULT dimers sulfate APAP to APAP-SO3

SULT dimers sulfate APAP to APAP-SO3

Stable Identifier

R-HSA-9753277

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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After a therapeutic dose, a large fraction (30-44%) of acetaminophen (APAP) can be converted to inactive sulfate conjugates. Cytosolic sulfotransferases (SULTs) carry out the sulfation conjugation of APAP. SULTs transfer a sulfo group from PAPS to APAP, making it more polar and therefore easier to eliminate. SULTs 1A1, 1A3, 1A4, 1C4, 1E1 and 2A1 are known to have sulfotransferase activity towards APAP (Reiter & Weinshilboum 1992, Adjei et al. 2008, Mazaleuskaya et al. 2015). SULTs are expressed in many tissues but Yamamoto et al. found higher sulfating activity in the liver and intestine than that found in the lung and kidney (Yamamoto et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
26067475	Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis Yamamoto, A, Liu, MY, Kurogi, K, Sakakibara, Y, Saeki, Y, Suiko, M, Liu, MC	J Biochem	2015
26049587	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses Mazaleuskaya, LL, Sangkuhl, K, Thorn, CF, FitzGerald, GA, Altman, RB, Klein, TE	Pharmacogenet Genomics	2015
18232020	Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects Adjei, AA, Gaedigk, A, Simon, SD, Weinshilboum, RM, Leeder, JS	Birth Defects Res A Clin Mol Teratol	2008
6950087	Acetaminophen and phenol: substrates for both a thermostable and a thermolabile form of human platelet phenol sulfotransferase Reiter, C, Weinshilboum, RM	J Pharmacol Exp Ther	1982