T3DB: Hypoxanthine

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2014-08-29 05:46:52 UTC

Update Date

2014-12-24 20:26:40 UTC

Accession Number

T3D4150

Identification

Common Name

Hypoxanthine

Class

Small Molecule

Description

Hypoxanthine 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

MOL SDF PDB SMILES InChI

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 Formula

C₅H₄N₄O

Average Molecular Mass

136.112 g/mol

Monoisotopic Mass

136.039 g/mol

CAS Registry Number

68-94-0

IUPAC Name

7H-purin-6-ol

Traditional Name

6-hydroxypurine

SMILES

OC1=NC=NC2=C1N=CN2

InChI Identifier

InChI=1S/C5H4N4O/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)

InChI Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Imidazopyrimidines

Sub Class

Purines and purine derivatives

Direct Parent

Hypoxanthines

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

oxopurine (CHEBI:17368 )
nucleobase analogue (CHEBI:17368 )
purine nucleobase (CHEBI:17368 )
Purine alkaloids (C00262 )
a purine-related compound (HYPOXANTHINE )
a purine base (HYPOXANTHINE )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Lysosome
Peroxisome

Biofluid Locations

Not Available

Tissue Locations

Adipose Tissue
Epidermis
Erythrocyte
Fibroblasts
Intestine
Kidney
Liver
Muscle
Placenta
Platelet
Prostate
Skeletal Muscle
Spleen
Testes

Pathways

Name	SMPDB Link	KEGG Link
Purine Metabolism	SMP00050	map00230
Xanthinuria type I	SMP00512	Not Available
Xanthinuria type II	SMP00513	Not Available
Molybdenium Cofactor Deficiency	SMP00203	Not Available
Xanthine Dehydrogenase Deficiency (Xanthinuria)	SMP00220	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	150°C
Boiling Point	Not Available
Solubility	0.7 mg/mL
LogP	-1.11

Predicted Properties

Property	Value	Source
Water Solubility	13 g/L	ALOGPS
logP	-0.55	ALOGPS
logP	-0.048	ChemAxon
logS	-1	ALOGPS
pKa (Strongest Acidic)	8.72	ChemAxon
pKa (Strongest Basic)	1.73	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	74.69 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	35.5 m³·mol⁻¹	ChemAxon
Polarizability	11.82 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0159-3970000000-0d844fae4a1ffe158823	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-014i-1790000000-ae93bf8bf07b30b65e1a	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-00di-9340000000-1184c503fb61344c4853	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-014i-3590000000-a419976950afe7934cbc	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-9800000000-9c266d6963658e9d2cf1	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0159-3970000000-0d844fae4a1ffe158823	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-014i-1790000000-ae93bf8bf07b30b65e1a	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9340000000-1184c503fb61344c4853	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-014i-3590000000-a419976950afe7934cbc	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-014i-2890000000-3be4d08be45781881bc1	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-014i-1590000000-bb6f003bfa7bd04628a1	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a5i-8900000000-e20eb5d939a2c406a6e2	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0613-5900000000-be0624b928ba71cc797d	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-000i-0900000000-2b36c20acd9973b317f5	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0api-9800000000-fb4e3cccb7d27d119feb	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0aor-9200000000-33c2f9eedf9a878530be	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positive	splash10-000i-9800000000-9c266d6963658e9d2cf1	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0910000000-4da64abddc3ac8ab573a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-014i-1900000000-859f61101b12be0b2978	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-014i-1900000000-f5d899e7988568d5bcab	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0900000000-e19e6d04568d3560eb4a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0910000000-8def0d2ec82152826763	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-014i-2900000000-a8361951a2f702a217c7	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0900000000-3f653a7c81b328e46cb5	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-014i-0080290000-be98ce43421dbf9007fa	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-000i-0930030000-56ea204dcb077bc174c2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0006-9000000000-4c2d1980f9e5e4b720a5	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-000i-0900000000-26b3c93bc9dea5a88032	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-000i-1900000000-c367cd4c23aea0f74ecb	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-000l-8900000000-91e35cdcc11d357119f0	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-0006-9100000000-4fb8f4ee2d35aa874617	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-014l-9000000000-7934b3037f39d69fc40a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-014i-9000000000-ad93e267446292bf247b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-014i-9000000000-4b8f9e13ed7adf0888c2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-014i-9000000000-f295755f591e27bb9f07	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-014i-9000000000-aee48a44f42a4b767844	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-014i-9000000000-f5ebd92e86cf00f28cf1	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-014i-9000000000-9a1ad1aa2d8fb621b608	2012-08-31	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-000i-8900000000-ebf57ea530a2d4e31ffa	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 22.53 MHz, DMSO-d6, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, D₂O, experimental)	Not Available	2016-10-22	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, D₂O, experimental)	Not Available	2016-10-22	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
2D NMR	[¹H, ¹H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)	Not Available	2012-12-04	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, 100%_DMSO, experimental)	Not Available	2012-12-04	View Spectrum

Toxicity Profile

Route of Exposure

Endogenous, Ingestion, Dermal (contact)

Mechanism of Toxicity

Hypoxanthine 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.

Metabolism

Under 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Naturally produced by the body (endogenous).

Minimum Risk Level

Not Available

Health Effects

As 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.

Symptoms

May lead to arthropathy, myopathy, crystal nephropathy, urolithiasis, or renal failure.

Treatment

Chronic 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

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

17368

BioCyc ID

HYPOXANTHINE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

HPA

ACToR ID

Not Available

Wikipedia Link

Hypoxanthine

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.

MSDS

T3D4150.pdf

General References

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
Pietz J, Guttenberg N, Gluck L: Hypoxanthine: a marker for asphyxia. Obstet Gynecol. 1988 Nov;72(5):762-6. [3140152 ]
Saari H: Oxygen derived free radicals and synovial fluid hyaluronate. Ann Rheum Dis. 1991 Jun;50(6):389-92. [1711835 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Purine nucleoside phosphorylase

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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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 ]
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 ]
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 ]
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. 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

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 ]
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. 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

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 ]
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. 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

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 ]
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 ]

Hypoxanthine (T3D4150)

Structure for T3D4150: Hypoxanthine

Targets

References

References

References

References