Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-08-29 05:47:53 UTC
Update Date2014-12-24 20:26:40 UTC
Accession NumberT3D4159
Identification
Common NameHippuric acid
ClassSmall Molecule
DescriptionHippuric acid is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Hippuric acid is an acyl glycine formed by the conjugation of benzoic aicd with glycine. Acyl glycines are produced through the action of glycine N-acyltransferase (EC 2.3.1.13) which is an enzyme that catalyzes the chemical reaction: acyl-CoA + glycine < -- > CoA + N-acylglycine. Hippuric acid is a normal component of urine and is typically increased with increased consumption of phenolic compounds (tea, wine, fruit juices). These phenols are converted to benzoic acid which is then converted to hippuric acid and excreted in the urine. Hippuric acid is the most frequently used biomarker in the biological monitoring of occupational exposure to toluene. This product of solvent biotransformation may be also found in the urine of individuals who have not been exposed to the solvent. A smaller fraction of the absorbed toluene is oxidized to aromatic compounds including ortho-cresol, which is not found significantly in the urine of nonexposed individuals. The concentration of hippuric acid in the urine of individuals exposed to a low toluene concentration does not differ from that of individuals not exposed to the solvent. This has led to the conclusion that hippuric acid should not be utilized in the biological monitoring of occupational exposure to low levels of toluene in the air. Protein-bound organic acids such as hippuric acid are markedly accumulated in uremic plasma and produce defective protein binding of drugs. (1, 2).
Compound Type
  • Amide
  • Amine
  • Ester
  • Food Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Solvent
  • Uremic Toxin
Chemical Structure
Thumb
Synonyms
Synonym
(benzoylamino)-Acetate
(benzoylamino)-Acetic acid
2-Benzamidoacetate
2-Benzamidoacetic acid
Benzamidoacetate
Benzamidoacetic acid
Benzoylglycine
Hippurate
N-Benzoylglycine
Phenylcarbonylaminoacetate
Phenylcarbonylaminoacetic acid
Chemical FormulaC9H9NO3
Average Molecular Mass179.173 g/mol
Monoisotopic Mass179.058 g/mol
CAS Registry Number495-69-2
IUPAC Name2-(phenylformamido)acetic acid
Traditional Namehippuric acid
SMILESOC(=O)CN=C(O)C1=CC=CC=C1
InChI IdentifierInChI=1S/C9H9NO3/c11-8(12)6-10-9(13)7-4-2-1-3-5-7/h1-5H,6H2,(H,10,13)(H,11,12)
InChI KeyInChIKey=QIAFMBKCNZACKA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hippuric acids. Hippuric acids are compounds containing hippuric acid, which consists of a of a benzoyl group linked to the N-terminal of a glycine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentHippuric acids
Alternative Parents
Substituents
  • Hippuric acid
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid or derivatives
  • Benzoyl
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
  • Prostate
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point187 - 191°C
Boiling Point240°C (decomposes)
Solubility3.75 mg/mL
LogP0.31
Predicted Properties
PropertyValueSource
Water Solubility1.18 g/LALOGPS
logP0.23ALOGPS
logP0.53ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)3.59ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity46.12 m³·mol⁻¹ChemAxon
Polarizability17.57 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0a4i-2910000000-fac0a1c19c9209e1daf5View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0a4i-0930000000-6f50aaca6d403e269682View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-0a4i-5930000000-166d57ae498305a4eee9View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0a4i-4920000000-358e012cae8853105371View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a6r-8900000000-01e7057139a995115ddbView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0il0-9700000000-5eb7d5acc34cdb44f3e0View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a6r-6900000000-9bebc859a11a987fc2d4View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-2910000000-fac0a1c19c9209e1daf5View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0930000000-6f50aaca6d403e269682View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-5930000000-166d57ae498305a4eee9View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-4920000000-358e012cae8853105371View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-2910000000-19b240c27664cf096501View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0930000000-b1d771fba596fcbf4d44View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-2900000000-3f2da6ec78f21732afeaView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0ab9-9810000000-58ac2f50544c1db5247fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-0059-1900000000-412e9313d23685caab38View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-004i-9100000000-cc560a494407b3c33abbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-004i-9200000000-103f81d635660cdb0aa0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (VARIAN MAT-44) , Positivesplash10-0a6r-8900000000-734176188abc8a1dd766View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-6E) , Positivesplash10-0a6r-6900000000-9bebc859a11a987fc2d4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-004i-0900000000-7f332f3c98391a276547View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-003r-2900000000-a8b444dcb0522a2aab6dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-004i-9200000000-fc8a26847a77460ed21aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a6r-9000000000-9c160b377301023f1df2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4i-9000000000-7ac8420c577cebb0e8a9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-004i-0900000000-7f332f3c98391a276547View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-003r-2900000000-a8b444dcb0522a2aab6dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-004i-9200000000-d20e52137daf3db2f638View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a6r-9000000000-1beabd6a9820b379f52fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-7ac8420c577cebb0e8a9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , negativesplash10-001i-0900000000-fae7f8c300bf6943f8d5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-003r-0900000000-5d25dcc019489d867073View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-003r-0900000000-ef98916bdf0fc8627083View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0900000000-cbfff04acbf0c95d7e30View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0900000000-65954d58bf9851d84f75View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0900000000-730b49f058aae1303abaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056r-9500000000-2707fadcc633cb9d989cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-8040a946088ae227b41eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-2900000000-48c46f688fb318e3a7baView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9300000000-4ded9b0d44ce0068065dView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a4i-5900000000-99084c1783177c807011View in MoNA
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as hippuric acid are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (4). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (5).
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNaturally produced by the body (endogenous).
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00714
PubChem Compound ID464
ChEMBL IDCHEMBL461
ChemSpider ID451
KEGG IDC01586
UniProt IDNot Available
OMIM ID
ChEBI ID18089
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkHippuric acid
References
Synthesis ReferenceIngersoll, A. W.; Barcock, S. H. Hippuric acid. Organic Syntheses (1932), XII 40-2.
MSDSLink
General References
  1. Amorim LC, Alvarez-Leite EM: Determination of o-cresol by gas chromatography and comparison with hippuric acid levels in urine samples of individuals exposed to toluene. J Toxicol Environ Health. 1997 Mar;50(4):401-7. [9120876 ]
  2. Niwa T: Organic acids and the uremic syndrome: protein metabolite hypothesis in the progression of chronic renal failure. Semin Nephrol. 1996 May;16(3):167-82. [8734460 ]
  3. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [22626821 ]
  4. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  5. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
  6. Angerer J, Kassebart V, Szadkowski D, Lehnert G: [Occupational chronic exposure to organic solvents. III. Gas-chromatographic determination of hippuric acid in serum (author's transl)]. Int Arch Arbeitsmed. 1975;34(3):199-207. [1184200 ]
  7. Akira K, Hashimoto T: Hippuric acid test using 13C-labelling and NMR spectroscopy. Clin Chem Lab Med. 2001 Mar;39(3):215-7. [11350017 ]
  8. Pelclova D, Cerna M, Pastorkova A, Vrbikova V, Prochazka B, Hurychova D, Dlaskova Z, Hornychova M: Study of the genotoxicity of toluene. Arch Environ Health. 2000 Jul-Aug;55(4):268-73. [11005432 ]
  9. Rutner M, Fitzek J, Jahnel-Kracht H, Otto J, Krause W: [Therapy of rheumatic disease with a hydroxyethylsalicylate gel. Results of 2 clinical studies of effectiveness and bioavailability]. Fortschr Med. 1995 Mar 20;113(8):111-3. [7759034 ]
  10. Bjorkman L, McLean C, Steen G: Organic acids in urine from human newborns. Clin Chem. 1976 Jan;22(1):49-52. [1245060 ]
  11. Bairaktari E, Katopodis K, Siamopoulos KC, Tsolas O: Paraquat-induced renal injury studied by 1H nuclear magnetic resonance spectroscopy of urine. Clin Chem. 1998 Jun;44(6 Pt 1):1256-61. [9625050 ]
  12. Caldwell J, Moffatt JR, Smith RL: Post-mortem survival of hippuric acid formation in rat and human cadaver tissue samples. Xenobiotica. 1976 May;6(5):275-80. [936647 ]
  13. Ukai H, Takada S, Inui S, Imai Y, Kawai T, Shimbo S, Ikeda M: Occupational exposure to solvent mixtures: effects on health and metabolism. Occup Environ Med. 1994 Aug;51(8):523-9. [7951776 ]
  14. Sebekova K, Lajdova I, Spustova V, Opatrny K Jr: Comparison of creatinine, hippuric acid, 5-hydroxyindoleacetic acid, serotonin, and pseudouridine concentrations in blood withdrawn from vein and arteriovenous fistula of uremic patients on maintenance hemodialysis. Artif Organs. 1991 Oct;15(5):434-5. [1741691 ]
  15. Pickert A, Bauerle A, Liebich HM: Determination of hippuric acid and furanic acid in serum of dialysis patients and control persons by high-performance liquid chromatography. J Chromatogr. 1989 Oct 27;495:95-104. [2613830 ]
  16. Mulder TP, Rietveld AG, van Amelsvoort JM: Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine. Am J Clin Nutr. 2005 Jan;81(1 Suppl):256S-260S. [15640488 ]
  17. Porter RD, Cathcart-Rake WF, Wan SH, Whittier FC, Grantham JJ: Secretory activity and aryl acid content of serum, urine, and cerebrospinal fluid in normal and uremic man. J Lab Clin Med. 1975 May;85(5):723-31. [1168235 ]
  18. Lof A, Hansen SH, Naslund P, Steiner E, Wallen M, Hjelm EW: Relationship between uptake and elimination of toluene and debrisoquin hydroxylation polymorphism. Clin Pharmacol Ther. 1990 Mar;47(3):412-7. [2311341 ]
  19. Kirshon B, Mari G, Moise KJ Jr: Indomethacin therapy in the treatment of symptomatic polyhydramnios. Obstet Gynecol. 1990 Feb;75(2):202-5. [2405320 ]
  20. Beving H, Olsson U, Bemgard A, Kristensson J, Palmborg J, Sollenberg J: High-performance liquid chromatographic analysis of hippuric acid in human blood plasma. J Chromatogr. 1990 Oct 26;532(1):45-53. [2079538 ]
  21. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory66 uMNot AvailableBindingDB 50009999
IC5020 uMNot AvailableBindingDB 50009999
References
  1. Motojima M, Hosokawa A, Yamato H, Muraki T, Yoshioka T: Uraemic toxins induce proximal tubular injury via organic anion transporter 1-mediated uptake. Br J Pharmacol. 2002 Jan;135(2):555-63. [11815391 ]
  2. Kouznetsova VL, Tsigelny IF, Nagle MA, Nigam SK: Elucidation of common pharmacophores from analysis of targeted metabolites transported by the multispecific drug transporter-Organic anion transporter1 (Oat1). Bioorg Med Chem. 2011 Jun 1;19(11):3320-40. doi: 10.1016/j.bmc.2011.04.045. Epub 2011 Apr 28. [21571536 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Vitamin d binding
Specific Function:
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:
KL
Uniprot ID:
Q9UEF7
Molecular Weight:
116179.815 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Superoxide-generating nadph oxidase activity
Specific Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:
NOX4
Uniprot ID:
Q9NPH5
Molecular Weight:
66930.995 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]