General Information of MET (ID: META00298)
Name Indoxyl sulfate
Synonyms   Click to Show/Hide Synonyms of This Metabolite
1H-indol-3-Ol hydrogen sulfate ester; 1H-indol-3-yl Hydrogen sulfate; 1H-indol-3-yl Hydrogen sulphate; 3-Indolyl hydrogen sulfate; 3-Indolyl hydrogen sulfuric acid; 3-Indolyl hydrogen sulphate; 3-Indolyl hydrogen sulphuric acid; 3-Indolyl sulfate; 3-Indolyl sulfuric acid; 3-Indolyl sulphate; 3-Indolyl sulphuric acid; 3-Indoxyl sulfate; 3-Indoxyl sulfuric acid; 3-Indoxyl sulphate; 3-Indoxyl sulphuric acid; 3-Indoxylsulfate; 3-Indoxylsulfuric acid; 3-Indoxylsulphate; 3-Indoxylsulphuric acid; Indican; Indican monopotassium salt; Indican monosodium salt; Indoxyl sulfic acid; Indoxyl sulfuric acid; Indoxyl sulphate; Indoxyl sulphuric acid; Indoxyl-3-sulfate; Indoxyl-3-sulfuric acid; Indoxyl-3-sulphate; Indoxyl-3-sulphuric acid; Indoxylsulfate; Indoxylsulfuric acid; Indoxylsulphate; Indoxylsulphuric acid; Monopotassium salt, indican; Monosodium salt, indican; Sulfate, indoxyl; indol-3-Ol; indol-3-yl Hydrogen sulfate; indol-3-yl Hydrogen sulfuric acid; indol-3-yl Hydrogen sulphate; indol-3-yl Hydrogen sulphuric acid; indol-3-yl Sulfate; indol-3-yl Sulfuric acid; indol-3-yl Sulphate; indol-3-yl Sulphuric acid
Source Endogenous;Food;Drug;Toxins/Pollutant;Microbial
Structure Type   Arylsulfates  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic acids and derivatives
Organic sulfuric acids and derivatives
Arylsulfates
PubChem CID
10258
HMDB ID
HMDB0000682
Formula
C8H7NO4S
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
DrugBank ID
DB07992
ChEBI ID
43355
FooDB ID
FDB022179
ChemSpider ID
9840
METLIN ID
524
Physicochemical Properties Molecular Weight 213.21 Topological Polar Surface Area 87.8
XlogP 1.3 Complexity 297
Heavy Atom Count 14 Rotatable Bond Count 2
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 4
Function
Indoxyl sulfate is a dietary protein metabolite and also a metabolite of the common amino acid tryptophan. It has been identified as a uremic toxin according to the European Uremic Toxin Working Group. It is a circulating uremic toxin stimulating glomerular sclerosis and interstitial fibrosis. Indoxyl sulfate is one of the well-known substances of a group of protein-bound uremic retention solutes. Indoxyl sulfate increases the rate of progression of renal failure. In plasma, indoxyl sulfate is a protein-bound uremic solute that induces endothelial dysfunction by inhibiting endothelial proliferation and migration in vitro. Some studies suggest that indoxyl sulfate is also involved in oxidative stress. In hemodialyzed patients, serum levels of indoxyl sulfate are associated with levels of pentosidine, a marker of carbonyl and oxidative stress. In vitro, indoxyl sulfate increases reactive oxygen species (ROS) production in tubular cells and increases NAD(P)H oxidase activity in endothelial cells. Indoxyl sulfate impairs osteoblast function and induces abnormalities of bone turnover. Indoxyl sulfate strongly decreases the levels of glutathione, one of the most active antioxidant systems of the cell. Indoxyl sulfate is a microbial metabolite found in Escherichia.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Apolipoprotein (Apo)
            Apolipoprotein A-II (APOA2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (-265T >C(rs5082)) of APOA2
                      Induced Change Indoxyl sulfate concentration: decrease (FC = 0.62)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Obesity [ICD-11: 5B81]
                      Details It is reported that mutation (-265T >C(rs5082)) of APOA2 leads to the decrease of indoxyl sulfate levels compared with control group.
      Lyases (EC 4)
            Cystathionine gamma-lyase (CTH) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of Cth
                      Induced Change Indoxyl sulfate concentration: increase (FC = 3.16)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Organic acid disorderss [ICD-11: 5C50]
                      Details It is reported that knockout of Cth leads to the increase of indoxyl sulfate levels compared with control group.
References
1 Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity. Am J Clin Nutr. 2018 Jul 1;108(1):188-200.
2 Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes. Oxid Med Cell Longev. 2021 Feb 13;2021:8877691.

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