Sulfation biotransformation reaction (WP692)

Homo sapiens

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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP692 CPTAC Assay Portal].

Authors

Pieter Giesbertz , Kristina Hanspers , Alex Pico , Daniela Digles , Denise Slenter , Eric Weitz , and Egon Willighagen

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

sulfonation conjugation pathway

Participants

Label Type Compact URI Comment
Sulfate Metabolite hmdb:HMDB0001448
ATP Metabolite hmdb:HMDB0000538
Glutathione (reduced) Metabolite hmdb:HMDB0000125
PAPS Metabolite hmdb:HMDB0001134
NADPH Metabolite hmdb:HMDB0000221
Glutathione (oxidized) Metabolite hmdb:HMDB0003337
APS Metabolite hmdb:HMDB0001003
ATP Metabolite hmdb:HMDB0000538
PAP Metabolite hmdb:HMDB0000061
NADP+ Metabolite hmdb:HMDB0000217
ADP Metabolite hmdb:HMDB0001341
SULT1E1 GeneProduct ensembl:ENSG00000109193
PAPSS2 GeneProduct ensembl:ENSG00000198682
SULT1A1 GeneProduct ensembl:ENSG00000196502
PAPSS1 GeneProduct ensembl:ENSG00000138801
G6PD GeneProduct ensembl:ENSG00000160211
SULT6B1 GeneProduct ensembl:ENSG00000138068
SULT4A1 GeneProduct ensembl:ENSG00000130540
SULT1A4 GeneProduct ensembl:ENSG00000213648
SULT1A2 GeneProduct ensembl:ENSG00000197165
GSR GeneProduct ensembl:ENSG00000104687
SULT2A1 GeneProduct ensembl:ENSG00000105398
SULT1C3 GeneProduct ensembl:ENSG00000196228
SULT1A3 GeneProduct ensembl:ENSG00000213599
SULT1C4 GeneProduct ncbigene:27233
SULT1C1 GeneProduct ensembl:ENSG00000198203
SULT1C2 GeneProduct ensembl:ENSG00000198075
SULT1B1 GeneProduct ensembl:ENSG00000173597
SULT2B1 GeneProduct ensembl:ENSG00000088002

References

  1. Interactions between dietary chemicals and human sulfotransferases-molecular mechanisms and clinical significance. Coughtrie MW, Johnston LE. Drug Metab Dispos. 2001 Apr;29(4 Pt 2):522–8. PubMed Europe PMC Scholia
  2. Sulfation through the looking glass--recent advances in sulfotransferase research for the curious. Coughtrie MWH. Pharmacogenomics J. 2002;2(5):297–308. PubMed Europe PMC Scholia
  3. Human sulfotransferases and their role in chemical metabolism. Gamage N, Barnett A, Hempel N, Duggleby RG, Windmill KF, Martin JL, et al. Toxicol Sci. 2006 Mar;90(1):5–22. PubMed Europe PMC Scholia