8-Hydroxyadenine

8-Hydroxyadenine Description

8-hydroxyadenine is an intermediate in the oxidation of adenine to 2,8-dihydroxyadenine by xanthine oxidase (EC 1.1.3.22). A controversy exists as to whether or not this metabolite is a marker of DNA damage. Several papers have reported an artifactual formation of a number of modified bases from intact DNA bases during derivatization of DNA hydrolysates to be analyzed by gas chromatography-mass spectrometry (GC/MS). These reports dealt with 8-hydroxyadenine (8-OH). It needs to be emphasized that the procedures for hydrolysis of DNA and derivatization of DNA hydrolysates used in these papers substantially differed from the established procedures previously described. Furthermore, a large number of relevant papers reporting the levels of these modified bases in DNA of various sources have been ignored. Interestingly, the levels of modified bases reported in the literature were not as high as those reported prior to prepurification. Levels of 8-OH-Ade were quite close to, or even the same as, or smaller than the level reported after prepurification. All these facts raise the question of the validity of the claims about the measurement of these modified DNA bases by GC/MS. Oxidative damage to DNA may play an important role in aging and neurodegenerative diseases such as Alzheimers disease (AD). Attack on DNA by reactive oxygen species, particliarly hydroxyl radicals, can lead to strand breaks, DNA-DNA and DNA-protein cross-linking, sister chromatid exchange and translocation, and formation of at least 20 oxidized base adducts. Modification of DNA bases can lead to mutation and altered protein synthesis. In late-stage AD brain, several studies have shown an elevation of the base adducts 8-hydroxyadenine (8-OHA). Several studies have shown a decline in repair of 8-OHG in AD. Most recently studies have shown elevated 8-OHA in nuclear and mitochondrial DNA in mild cognitive impairment, the earliest detectable form of AD, suggesting that oxidative damage to DNA is an early event in AD and not a secondary phenomenon. (PMID: 10098459 , 17034348 ). Structure

Synonyms

Chemical Formlia

C₅H₅N₅O Average Molecliar Weight

151.1261 Monoisotopic Molecliar Weight

151.049409807 IUPAC Name

6-amino-7H-purin-8-ol Traditional Name

6-amino-8-hydroxypurine CAS Registry Number

21149-26-8 SMILES

InChI Identifier

InChI Key

RGKBRPAAQSHTED-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as purinones. These are purines in which the purine moiety bears a C=O group. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Imidazopyrimidines Direct Parent

Purinones Alternative Parents

Substituents

Molecliar Framework

Aromatic heteropolycyclic compounds External Descriptors

Not Available Ontology Status

Expected but not Quantified Origin

Biofunction

Not Available Application

Not Available Cellliar locations

Physical Properties State

Solid Experimental Properties

Predicted Properties

Spectra Spectra

Not Available Biological Properties Cellliar Locations

Biofluid Locations

Not Available Tissue Location

Not Available Pathways

Not Available Normal Concentrations Not Available Abnormal Concentrations

Not Available Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

Not Available DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

FDB022105 KNApSAcK ID

Not Available Chemspider ID

4511108 KEGG Compound ID

Not Available BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Not Available NuGOwiki Link

HMDB00542 Metagene Link

HMDB00542 METLIN ID

5527 PubChem Compound

5355054 PDB ID

Not Available ChEBI ID

351476

Product: MQAE

1. Bartlett GR: Metabolism by man of intravenously administered adenine. Transfusion. 1977 Jul-Aug;17(4):367-73. [PubMed:878002 ]
2. Ravanat JL, Guicherd P, Tuce Z, Cadet J: Simultaneous determination of five oxidative DNA lesions in human urine. Chem Res Toxicol. 1999 Sep;12(9):802-8. [PubMed:10490501 ]
3. Stillwell WG, Xu HX, Adkins JA, Wishnok JS, Tannenbaum SR: Analysis of methylated and oxidized purines in urine by capillary gas chromatography-mass spectrometry. Chem Res Toxicol. 1989 Mar-Apr;2(2):94-9. [PubMed:2519715 ]
4. Webb AL, Singh RH, Kennedy MJ, Elsas LJ: Verbal dyspraxia and galactosemia. Pediatr Res. 2003 Mar;53(3):396-402. [PubMed:12595586 ]
5. WYNGAARDEN JB, DUNN JT: 8-Hydroxyadenine as the intermediate in the oxidation of adenine to 2, 8-dihydroxyadenine by xanthine oxidase. Arch Biochem Biophys. 1957 Jul;70(1):150-6. [PubMed:13445250 ]
6. Dizdaroglu M: Facts about the artifacts in the measurement of oxidative DNA base damage by gas chromatography-mass spectrometry. Free Radic Res. 1998 Dec;29(6):551-63. [PubMed:10098459 ]
7. Markesbery WR, Lovell MA: DNA oxidation in Alzheimers disease. Antioxid Redox Signal. 2006 Nov-Dec;8(11-12):2039-45. [PubMed:17034348 ]

PMID: 25172903