Sulfation biotransformation reaction (Homo sapiens)

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1-3sulfurylasePAPS synthesis (co-substrate)APS kinasemodification of Cys83 in SULT1E1SubstrateG6PDSULT1A4SULT2B1ATPGPXSULT1A2SULT1E1SULT1C3SULT1A1NADP+Glutathione (oxidized)ADPATPPAPSS1SULT4A1SULT1C1PAPSS2SULT2A1SulfateSULT1B1Substrate sulfateGSRSULT1C2SULT1C4PPiNADPHPAPSSulfotransferaseGlutathione (reduced)APSPAPSULT1A3SULT6B1


Description

Metabolism of xenobiotic compounds consists of phase I and a phase II biotransformation reactions, being compound modification and conjugation reactions respectively. In phase I biotransformation, the compound is modificated via oxidation, reduction, hydrolysis, or other minor reactions, to reveal a reactive group to which a conjugation molecule can react to. In phase II, a small conjugation molecule reacts with the phase I modified molecule, producing a much more water-soluble molecule that can be excreted more easily. Sulfation is a phase II biotransformation reaction in which sulfate acts as a conjugation molecule and binds to a substrate via the catalysis of sulfotransferases. Sulfate is first combined with ATP molecules to form PAPS via the dual function enzymes PAPSS1 and PAPSS2 consisting of a sulfurylase domain and an APS kinase domain. From PAPS the sulfate group is transferred to the actual substrate via the action of sulfotransferases, resulting in a sulfated substrate and the sulfate-lacking PAP.

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Bibliography

  1. Gamage N, Barnett A, Hempel N, Duggleby RG, Windmill KF, Martin JL, McManus ME; ''Human sulfotransferases and their role in chemical metabolism.''; Toxicol Sci, 2006 PubMed Europe PMC Scholia
  2. Coughtrie MW, Johnston LE; ''Interactions between dietary chemicals and human sulfotransferases-molecular mechanisms and clinical significance.''; Drug Metab Dispos, 2001 PubMed Europe PMC Scholia
  3. Coughtrie MW; ''Sulfation through the looking glass--recent advances in sulfotransferase research for the curious.''; Pharmacogenomics J, 2002 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
126232view09:41, 17 April 2023EgonwLicense is CCZero
117833view15:09, 22 May 2021EweitzModified title
106825view13:30, 17 September 2019MaintBotHMDB identifier normalization
105828view23:06, 15 August 2019KhanspersModified description
94192view14:23, 25 August 2017DeSlChanged two metabolite nodes to text labels, since they were not metabolite nodes.
69031view17:50, 8 July 2013MaintBotUpdated to 2013 gpml schema
67666view11:46, 26 June 2013DdiglesOntology Term : 'sulfonation conjugation pathway' added !
59211view19:50, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
48223view05:29, 17 May 2012MaintBotAutomatic update of PubChem xrefs
41213view23:45, 1 March 2011MaintBotRemoved redundant pathway information and comments
39771view08:02, 17 January 2011AlexanderPicomore complete title
38739view21:58, 23 September 2010KhanspersChanged line types
33409view14:49, 30 November 2009MaintBotRemoved group label
32746view23:23, 3 September 2009MaintBotModified categories
29857view08:11, 8 June 2009Pieter GiesbertzModified description
29856view08:09, 8 June 2009Pieter GiesbertzModified description
29656view10:06, 24 May 2009Pieter GiesbertzAdded literature references
29350view10:31, 28 April 2009Pieter GiesbertzSpecify description
29337view14:09, 24 April 2009Pieter GiesbertzAdded compound identifiers
29336view14:05, 24 April 2009Pieter GiesbertzAdded compound identifiers
29284view07:46, 22 April 2009Pieter GiesbertzSpecify description
29283view07:42, 22 April 2009Pieter GiesbertzSpecify description
29149view09:32, 7 April 2009Pieter GiesbertzSpecify description
29148view09:27, 7 April 2009Pieter GiesbertzSpecify description
29147view09:24, 7 April 2009Pieter GiesbertzPeriodical save, work in progress
29146view14:45, 6 April 2009Pieter GiesbertzSpecify description
29145view14:44, 6 April 2009Pieter GiesbertzSpecify description
29144view14:35, 6 April 2009Pieter GiesbertzPeriodical save, work in progress
29143view14:15, 6 April 2009Pieter GiesbertzPeriodical save, work in progress
29142view13:46, 6 April 2009Pieter GiesbertzSpecify description
29141view13:45, 6 April 2009Pieter GiesbertzSpecify description
29140view13:43, 6 April 2009Pieter GiesbertzPeriodical save, work in progress
29139view13:33, 6 April 2009Pieter GiesbertzPeriodical save, work in progress
29138view13:23, 6 April 2009Pieter GiesbertzNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADPMetaboliteHMDB01341 (HMDB)
APSMetaboliteHMDB01003 (HMDB)
ATPMetaboliteHMDB00538 (HMDB)
G6PDGeneProductENSG00000160211 (Ensembl)
GPXGeneProduct
GSRGeneProductENSG00000104687 (Ensembl)
Glutathione (oxidized)MetaboliteHMDB03337 (HMDB)
Glutathione (reduced)MetaboliteHMDB00125 (HMDB)
NADP+MetaboliteHMDB00217 (HMDB)
NADPHMetaboliteHMDB00221 (HMDB)
PAPMetaboliteHMDB00061 (HMDB)
PAPSMetaboliteHMDB01134 (HMDB)
PAPSS1GeneProductENSG00000138801 (Ensembl)
PAPSS2GeneProductENSG00000198682 (Ensembl)
PPiMetabolite
SULT1A1GeneProductENSG00000196502 (Ensembl)
SULT1A2GeneProductENSG00000197165 (Ensembl)
SULT1A3GeneProductENSG00000213599 (Ensembl)
SULT1A4GeneProductENSG00000213648 (Ensembl)
SULT1B1GeneProductENSG00000173597 (Ensembl)
SULT1C1GeneProductENSG00000198203 (Ensembl)
SULT1C2GeneProductENSG00000198075 (Ensembl)
SULT1C3GeneProductENSG00000196228 (Ensembl)
SULT1C4GeneProduct27233 (Entrez Gene)
SULT1E1GeneProductENSG00000109193 (Ensembl)
SULT2A1GeneProductENSG00000105398 (Ensembl)
SULT2B1GeneProductENSG00000088002 (Ensembl)
SULT4A1GeneProductENSG00000130540 (Ensembl)
SULT6B1GeneProductENSG00000138068 (Ensembl)
SubstrateMetabolite
Substrate sulfateMetabolite
SulfateMetaboliteHMDB01448 (HMDB)
SulfotransferaseGeneProduct

Annotated Interactions

No annotated interactions

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