Guanidine (T3D4172)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (8)XML
Targets (8)
Record Information
Version2.0
Creation Date2014-08-29 05:49:15 UTC
Update Date2014-12-24 20:26:41 UTC
Accession NumberT3D4172
Identification
Common NameGuanidine
ClassSmall Molecule
DescriptionGuaniidine 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. Guanidine is a polyamine that can function as a strong organic base existing primarily as guanidium ions at physiological pH. With a pKa of 12.5, guanidine is protonated, with a charge of +1 in physiological conditions. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed). Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives.
Compound Type
  • Amide
  • Amine
  • Drug
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(4-Aminobutyl) guanidine
Aminoformamidine
Aminomethanamidine
Carbamamidine
Carbamidine
Gu
Guanidin
GUANIDINE
H2N-C(=NH)-NH2
Imidourea
Iminourea
Chemical FormulaCH5N3
Average Molecular Mass59.071 g/mol
Monoisotopic Mass59.048 g/mol
CAS Registry Number113-00-8
IUPAC Nameguanidine
Traditional Nameguanidine
SMILESNC(N)=N
InChI IdentifierInChI=1S/CH5N3/c2-1(3)4/h(H5,2,3,4)
InChI KeyInChIKey=ZRALSGWEFCBTJO-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as guanidines. Guanidines are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassGuanidines
Direct ParentGuanidines
Alternative Parents
Substituents
  • Guanidine
  • Carboximidamide
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Imine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • Brain
  • Cartilage
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Pancreas
  • Placenta
  • Platelet
  • Spleen
  • Testes
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point50°C
Boiling PointNot Available
Solubility1840 mg/L (at 20°C)
LogP-0.6
Predicted Properties
PropertyValueSource
Water Solubility11.5 g/LALOGPS
logP-1.9ALOGPS
logP-1.2ChemAxon
logS-0.71ALOGPS
pKa (Strongest Basic)12.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area75.89 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity25.86 m³·mol⁻¹ChemAxon
Polarizability5.57 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00dj-0920000000-b2c19a9125b059b573fd2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00dj-0920000000-b2c19a9125b059b573fd2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9000000000-6e00e9be1957670e422b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03di-9000000000-4df2949d18a754b6aa192012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-18b92fabd8878a75412f2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-6675e99565dbe07353112012-07-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-9000000000-0bf566c21de3691982142015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-9000000000-b4670d41c5cfae8560862015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03dl-9000000000-9431377731da436c5aa72015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-9000000000-2280b2044ac4a1f8b7fb2015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-8278836749ed05b02fb32015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-154d1302bda42480ad7b2015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-9000000000-ab782a456c989f06bfc82021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9000000000-36e3aa30c6cc4afb20492021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-36e3aa30c6cc4afb20492021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-9000000000-1c8520c5f7efb1187e432021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-1c8520c5f7efb1187e432021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-1c8520c5f7efb1187e432021-09-23View Spectrum
Toxicity Profile
Route of ExposureRapidly absorbed and distributed
Mechanism of ToxicityUremic toxins such as guaniidine 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) (2). 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 (3).
MetabolismNot metabolized. Half Life: 7-8 hours
Toxicity ValuesLD50 = 475 mg/kg (oral, rat).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis.
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 IDDB00536
HMDB IDHMDB01842
PubChem Compound ID3520
ChEMBL IDCHEMBL821
ChemSpider ID3400
KEGG IDC17349
UniProt IDNot Available
OMIM ID
ChEBI ID24435
BioCyc IDCPD-593
CTD IDNot Available
Stitch IDNot Available
PDB IDGAI
ACToR IDNot Available
Wikipedia LinkGuanidine
References
Synthesis Reference

Helmut Hoffmann, Carlhans Suling, “Process for the production of guanidine salts of aliphatic mercaptosulphonic acids.” U.S. Patent US3956368, issued November, 1954.

MSDSLink
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. De Deyn PP, Marescau B, D'Hooge R, Possemiers I, Nagler J, Mahler C: Guanidino compound levels in brain regions of non-dialyzed uremic patients. Neurochem Int. 1995 Sep;27(3):227-37. [8520461 ]
  5. Bullough A, Karadia S, Watters M: Phaeochromocytoma: an unusual cause of hypertension in pregnancy. Anaesthesia. 2001 Jan;56(1):43-6. [11167434 ]
  6. Mannik M, Person RE: Deep penetration of antibodies into the articular cartilage of patients with rheumatoid arthritis. Rheumatol Int. 1994;14(3):95-102. [7839077 ]
  7. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [10385678 ]
  8. Eropkin MIu, Smirnova TD, Eropkina EM, Mamaeva EG: [The study of the Ca2+ role in cytotoxic response of human cells in culture to the action of xenobiotics]. Tsitologiia. 2000;42(2):154-9. [10752119 ]
  9. Rufanova VA, Sorokin A: CrkII associates with BCAR3 in response to endothelin-1 in human glomerular mesangial cells. Exp Biol Med (Maywood). 2006 Jun;231(6):752-6. [16740993 ]
  10. Bjornsson S: Size-dependent separation of proteoglycans by electrophoresis in gels of pure agarose. Anal Biochem. 1993 May 1;210(2):292-8. [8512064 ]
  11. Sakamoto N, Toge T, Nishiyama M: Tumor-specific synergistic therapy of mitomycin C: modulation of bioreductive activation. Hiroshima J Med Sci. 1997 Jun;46(2):67-73. [9232934 ]
  12. Lorenzo P, Bayliss MT, Heinegard D: A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem. 1998 Sep 4;273(36):23463-8. [9722583 ]
  13. Dabaghian RH, Barnard G, McConnell I, Clewley JP: An immunoassay for the pathological form of the prion protein based on denaturation and time resolved fluorometry. J Virol Methods. 2006 Mar;132(1-2):85-91. Epub 2005 Oct 10. [16219367 ]
  14. Gothert M, Bruss M, Bonisch H, Molderings GJ: Presynaptic imidazoline receptors. New developments in characterization and classification. Ann N Y Acad Sci. 1999 Jun 21;881:171-84. [10415912 ]
  15. Okumi M, Ueda T, Ichimaru N, Fujimoto N, Itoh K: [A case of composite pheochromocytoma-ganglioneuroblastoma in the adrenal gland with primary hyperparathyroidism]. Hinyokika Kiyo. 2003 May;49(5):269-72. [12822455 ]
  16. Leitersdorf E, Reshef A, Meiner V, Levitzki R, Schwartz SP, Dann EJ, Berkman N, Cali JJ, Klapholz L, Berginer VM: Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin. J Clin Invest. 1993 Jun;91(6):2488-96. [8514861 ]
  17. Atlas D: Molecular and physiological properties of clonidine-displacing substance. Ann N Y Acad Sci. 1995 Jul 12;763:314-24. [7677341 ]
  18. Mizutani N, Hayakawa C, Ohya Y, Watanabe K, Watanabe Y, Mori A: Guanidino compounds in hyperargininemia. Tohoku J Exp Med. 1987 Nov;153(3):197-205. [3433275 ]
  19. Rubello D, Bui C, Casara D, Gross MD, Fig LM, Shapiro B: Functional scintigraphy of the adrenal gland. Eur J Endocrinol. 2002 Jul;147(1):13-28. [12088915 ]
  20. Wang JG, Lemon SM: Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. J Virol. 1993 Jan;67(1):446-54. [7677957 ]
  21. Maruta K, Sonoda Y, Saigo R, Yoshioka T, Fukunaga H: [A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma]. Nihon Ronen Igakkai Zasshi. 2004 May;41(3):339-43. [15237755 ]
  22. Noyori K, Koshino T, Takagi T, Okamoto R, Jasin HE: Binding characteristics of antitype II collagen antibody to the surface of diseased human cartilage as a probe for tissue damage. J Rheumatol. 1994 Feb;21(2):293-6. [8182639 ]
  23. Tapiero H, Mathe G, Couvreur P, Tew KD: I. Arginine. Biomed Pharmacother. 2002 Nov;56(9):439-45. [12481980 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Ribonuclease pancreatic
General Function:
Ribonuclease a activity
Specific Function:
Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single-stranded and double-stranded RNA.
Gene Name:
RNASE1
Uniprot ID:
P07998
Molecular Weight:
17644.125 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. Dodge RW, Laity JH, Rothwarf DM, Shimotakahara S, Scheraga HA: Folding pathway of guanidine-denatured disulfide-intact wild-type and mutant bovine pancreatic ribonuclease A. J Protein Chem. 1994 May;13(4):409-21. [7986344 ]
  4. Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh F: Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal. 2005;19(6):229-32. [16302208 ]
  5. Loh SN, Rohl CA, Kiefhaber T, Baldwin RL: A general two-process model describes the hydrogen exchange behavior of RNase A in unfolding conditions. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1982-7. [8700871 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
Target Details
2. Guanidinoacetate N-methyltransferase
General Function:
Methyltransferase activity
Specific Function:
Not Available
Gene Name:
GAMT
Uniprot ID:
Q14353
Molecular Weight:
26317.925 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. Komoto J, Yamada T, Takata Y, Konishi K, Ogawa H, Gomi T, Fujioka M, Takusagawa F: Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes. Biochemistry. 2004 Nov 16;43(45):14385-94. [15533043 ]
  4. Karelin AA, Mardashev SR: [The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas]. Biokhimiia. 1976 Feb;41(2):316-23. [179611 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
Target Details
3. Disks large homolog 4
General Function:
Scaffold protein binding
Specific Function:
Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B (By similarity).
Gene Name:
DLG4
Uniprot ID:
P78352
Molecular Weight:
80494.615 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 ]
Target Details
4. Aldehyde dehydrogenase, mitochondrial
General Function:
Electron carrier activity
Specific Function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular Weight:
56380.93 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. 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 ]
5. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 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. 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 ]
Target Details
6. Klotho
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 ]
Target Details
7. NADPH oxidase 4
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 ]
Target Details
8. Solute carrier family 22 member 8
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 ]