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Record Information
Version2.0
Creation Date2014-08-29 05:46:52 UTC
Update Date2014-12-24 20:26:40 UTC
Accession NumberT3D4150
Identification
Common NameHypoxanthine
ClassSmall Molecule
DescriptionHypoxanthine 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. Hypoxanthine is a naturally occurring purine derivative and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. Hypoxanthine is also a spontaneous deamination product of adenine. Lesch-Nyhan disease is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase.
Compound Type
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
Synonyms
Synonym
1,7-Dihydro-6H-purin-6-one
1,7-Dihydro-6H-purine-6-one
1H,7H-Hypoxanthine
3H-Purin-6-ol
4-Hydroxy-1H-purine
6(1H)-Purinone
6-Hydroxy-1H-purine
6-Hydroxypurine
6-Oxopurine
7H-Purin-6-ol
9H-Purin-6(1H)-one
9H-Purin-6-ol
Hypoxanthine enol
Purin-6(1H)-one
Purin-6(3H)-one
Purin-6-ol
Purine-6-ol
Sarcine
Sarkin
Sarkine
Chemical FormulaC5H4N4O
Average Molecular Mass136.112 g/mol
Monoisotopic Mass136.039 g/mol
CAS Registry Number68-94-0
IUPAC Name7H-purin-6-ol
Traditional Name6-hydroxypurine
SMILESOC1=NC=NC2=C1N=CN2
InChI IdentifierInChI=1S/C5H4N4O/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
InChI KeyInChIKey=FDGQSTZJBFJUBT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hypoxanthines. Hypoxanthines are compounds containing the purine derivative 1H-purin-6(9H)-one. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentHypoxanthines
Alternative Parents
Substituents
  • 6-oxopurine
  • Hypoxanthine
  • Pyrimidone
  • Pyrimidine
  • Azole
  • Imidazole
  • Vinylogous amide
  • Heteroaromatic compound
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Lysosome
  • Peroxisome
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Epidermis
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Purine MetabolismSMP00050 map00230
Xanthinuria type ISMP00512 Not Available
Xanthinuria type IISMP00513 Not Available
Molybdenium Cofactor DeficiencySMP00203 Not Available
Xanthine Dehydrogenase Deficiency (Xanthinuria)SMP00220 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point150°C
Boiling PointNot Available
Solubility0.7 mg/mL
LogP-1.11
Predicted Properties
PropertyValueSource
Water Solubility13 g/LALOGPS
logP-0.55ALOGPS
logP-0.048ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)8.72ChemAxon
pKa (Strongest Basic)1.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.69 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity35.5 m³·mol⁻¹ChemAxon
Polarizability11.82 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-0159-3970000000-0d844fae4a1ffe158823JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-014i-1790000000-ae93bf8bf07b30b65e1aJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-00di-9340000000-1184c503fb61344c4853JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-014i-3590000000-a419976950afe7934cbcJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-9800000000-9c266d6963658e9d2cf1JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0159-3970000000-0d844fae4a1ffe158823JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1790000000-ae93bf8bf07b30b65e1aJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9340000000-1184c503fb61344c4853JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-014i-3590000000-a419976950afe7934cbcJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-2890000000-3be4d08be45781881bc1JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1590000000-bb6f003bfa7bd04628a1JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a5i-8900000000-e20eb5d939a2c406a6e2JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0613-5900000000-be0624b928ba71cc797dJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0900000000-2b36c20acd9973b317f5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0api-9800000000-fb4e3cccb7d27d119febJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0aor-9200000000-33c2f9eedf9a878530beJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-000i-9800000000-9c266d6963658e9d2cf1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-000i-0910000000-4da64abddc3ac8ab573aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-1900000000-859f61101b12be0b2978JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-1900000000-f5d899e7988568d5bcabJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-000i-0900000000-e19e6d04568d3560eb4aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-000i-0910000000-8def0d2ec82152826763JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-2900000000-a8361951a2f702a217c7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-000i-0900000000-3f653a7c81b328e46cb5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-0080290000-be98ce43421dbf9007faJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-000i-0930030000-56ea204dcb077bc174c2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0006-9000000000-4c2d1980f9e5e4b720a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-000i-0900000000-26b3c93bc9dea5a88032JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-000i-1900000000-c367cd4c23aea0f74ecbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-000l-8900000000-91e35cdcc11d357119f0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0006-9100000000-4fb8f4ee2d35aa874617JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-014l-9000000000-7934b3037f39d69fc40aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-014i-9000000000-ad93e267446292bf247bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-014i-9000000000-4b8f9e13ed7adf0888c2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-014i-9000000000-f295755f591e27bb9f07JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-014i-9000000000-aee48a44f42a4b767844JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-014i-9000000000-f5ebd92e86cf00f28cf1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-014i-9000000000-9a1ad1aa2d8fb621b608JSpectraViewer | MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-8900000000-ebf57ea530a2d4e31ffaJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityHypoxanthine is a poorly soluble compound. As a result high concentrations of serum hypoxanthine can lead to the formation of kidney stones which can, over the long term, induce kidney failure.
MetabolismUnder normal circumstances hypoxanthine is readily converted to uric acid. The enzyme xanthine oxidase makes uric acid from xanthine and hypoxanthine, which in turn are produced from other purines. In humans and higher primates, uric acid is the final oxidation (breakdown) product of purine metabolism and is excreted in urine.
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 EffectsAs 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. Chronically high concentrations of hpyoxanthine can lead to health problems such as renal failure and xanthine kidney stones, one of the rarest types of kidney stones. Chronically high levels of hypoxanthine are associated with at least 4 inborn errors of metabolism including: Xanthinuria type I, Xanthuria type II, Molybdenium Cofactor Deficiency, and Xanthinuria.
SymptomsMay lead to arthropathy, myopathy, crystal nephropathy, urolithiasis, or renal failure.
TreatmentChronic Exposure: Kidney dialysis is usually needed to relieve the symptoms of xanthine toxicity until normal kidney function can be restored. Acute Exposure: EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04076
HMDB IDHMDB00157
PubChem Compound ID790
ChEMBL IDCHEMBL1427
ChemSpider ID768
KEGG IDC00262
UniProt IDNot Available
OMIM ID
ChEBI ID17368
BioCyc IDHYPOXANTHINE
CTD IDNot Available
Stitch IDNot Available
PDB IDHPA
ACToR IDNot Available
Wikipedia LinkHypoxanthine
References
Synthesis Reference

Alvin J. Glasky, Heinrich Bollinger, Hans Rudolf Muller, “Methods of synthesis for 9-substituted hypoxanthine derivatives.” U.S. Patent US06849735, issued February 01, 2005.

MSDST3D4150.pdf
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Bullo B, Marlewski M, Smolenski RT, Rutkowski B, Swierczynski J, Manitius J: Erythrocyte nucleotides and blood hypoxanthine in patients with uremia evaluated immediately and 24 hours after hemodialysis. Ren Fail. 1996 Mar;18(2):247-52. [8723362 ]
  5. Ihara H, Shino Y, Morita Y, Kawaguchi E, Hashizume N, Yoshida M: Is skeletal muscle damaged by the oxidative stress following anaerobic exercise? J Clin Lab Anal. 2001;15(5):239-43. [11574951 ]
  6. Inokuchi T, Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Yamamoto A, Cheng J, Hashimoto-Tamaoki T, Hada T, Yamamoto T: Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient. Metabolism. 2004 Nov;53(11):1500-2. [15536609 ]
  7. Niklasson F: Simultaneous liquid-chromatographic determination of hypoxanthine, xanthine, urate, and creatinine in cerebrospinal fluid, with direct injection. Clin Chem. 1983 Aug;29(8):1543-6. [6872216 ]
  8. Pietz J, Guttenberg N, Gluck L: Hypoxanthine: a marker for asphyxia. Obstet Gynecol. 1988 Nov;72(5):762-6. [3140152 ]
  9. Saari H: Oxygen derived free radicals and synovial fluid hyaluronate. Ann Rheum Dis. 1991 Jun;50(6):389-92. [1711835 ]
  10. Ohdoi C, Nyhan WL, Kuhara T: Chemical diagnosis of Lesch-Nyhan syndrome using gas chromatography-mass spectrometry detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):123-30. [12829005 ]
  11. Castro-Gago M, Rodriguez IN, Rodriguez-Nunez A, Guitian JP, Rocamonde SL, Rodriguez-Segade S: Therapeutic criteria in hydrocephalic children. Childs Nerv Syst. 1989 Dec;5(6):361-3. [2611770 ]
  12. Storm H, Rognum TO, Saugstad OD, Skullerud K, Reichelt KL: Beta-endorphin immunoreactivity in spinal fluid and hypoxanthine in vitreous humour related to brain stem gliosis in sudden infant death victims. Eur J Pediatr. 1994 Sep;153(9):675-81. [7957429 ]
  13. Koellner G, Luic M, Shugar D, Saenger W, Bzowska A: Crystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 A resolution. J Mol Biol. 1997 Jan 17;265(2):202-16. [9020983 ]
  14. Kaya M, Moriwaki Y, Ka T, Inokuchi T, Yamamoto A, Takahashi S, Tsutsumi Z, Tsuzita J, Oku Y, Yamamoto T: Plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine) and oxypurinol after rigorous exercise. Metabolism. 2006 Jan;55(1):103-7. [16324927 ]
  15. Nakayama Y, Kinoshita A, Tomita M: Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor Biol Med Model. 2005 May 9;2:18. [15882454 ]
  16. Smolenska Z, Kaznowska Z, Zarowny D, Simmonds HA, Smolenski RT: Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis. Rheumatology (Oxford). 1999 Oct;38(10):997-1002. [10534552 ]
  17. Eells JT, Spector R: Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem Res. 1983 Nov;8(11):1451-7. [6656991 ]
  18. Saiki S, Sato T, Kohzuki M, Kamimoto M, Yosida T: Changes in serum hypoxanthine levels by exercise in obese subjects. Metabolism. 2001 Jun;50(6):627-30. [11398135 ]
  19. Gudbjornsson B, Zak A, Niklasson F, Hallgren R: Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides. Ann Rheum Dis. 1991 Oct;50(10):669-72. [1958086 ]
  20. Saiki S, Sato T, Hiwatari M, Harada T, Oouchi M, Kamimoto M: Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly. Tohoku J Exp Med. 1999 May;188(1):71-4. [10494902 ]
  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:
Purine-nucleoside phosphorylase activity
Specific Function:
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Gene Name:
PNP
Uniprot ID:
P00491
Molecular Weight:
32117.69 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
  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 ]
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 ]