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 WillighagenActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
sulfonation conjugation pathway| 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 | |
| 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
- 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
- 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
- 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