Deoxyinosines

Adenosine deaminase (ADA) is an amino hydrolase that catalyzes the deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine, respectively. High activity of ADA is seen in thymus and other lymphoid tissues. ADA has been shown in many different physical forms. A small form of the enzyme predominates in the spleen, stomach, and red blood cells, whereas the large form predominates in the kidney, liver, and skin fibroblasts. The small form of the catalytic subunit can be converted to the large form by complexing with a protein termed binding protein or complexing protein. 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

ATP 7 was converted to two, at that time unknown organo-fluorine compounds, 5 -fluoro-5 -deoxyadenosine (5 -FDA) 5 and 5 -fluoro-5 -deoxyinosine (5 -FDI) 6 as well as FAc 1 [6],... 

A related experiment involved a coupled fluorinase/adenyl acid deaminase Aspergillus sp.) assay. In this reaction, the resultant 5 -CIDA 14 is converted to 5 -chloro-5 -deoxyinosine (5 -CIDI) 15. These experiments indicate that the fluorinase can process chloride ion in a similar manner to fluoride. 

Takahashi R, Sakuma A, Itoh K, et al Comparison of efficacy of lithium carbonate and chlorpromazine in mania report of collaborative study group on treatment of mania in Japan. Arch Gen Psychiatry 32 1310-1318, 1975 Takahashi Y, Kato K, Hayashizaki Y, et al Molecular cloning of the human cholecystokinin gene by use of a synthetic probe containing deoxyinosine. Proc Natl Acad Sci U S A 82 1931-1935, 1985... 

Adenosine deaminase (ADA) is a ubiquitous enzyme that is essential for the breakdown of the purine base adenosine, from both food intake and the turnover of nucleic acids. ADA hydrolyzes adenosine and deoxyadenosine into inosine and deoxyinosine, respectively, via the removal of an amino group. Deficiency of the ADA enzyme results in the build-up of deoxyadenosine and deoxyATP (adenosine triphosphate), both of which inhibit the normal maturation and survival of lymphocytes. Most importantly, these metabolites affect the ability of T-cells to differentiate into mature T-cells [656430], [666686]. ADA deficiency results in a form of severe combined immunodeficiency (SCID), known as ADA-SCID [467343]. 

Because of their basicity (lower than that of aliphatic amines), aromatic primary amines can be selectively nitrosated179 in the presence of aliphatic amines at low pH. An example is provided by the deamination of 3 -amino-3 -deoxyadenosine, although the yield of the product isolated, 3 -amino-3 -deoxyinosine, was180 only about 4%. Some 50% of the starting material remained unchanged, and hydrolysis released adenine (30%). 

Adenosine deaminase catalyzes the hydrolytic deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine respectively. Inhibition of adenosine deaminase leads to an accumulation of its substrates which results in adenosine receptor-mediated effects. Most inhibitors are not reported to have antinociceptive properties, but 2 -deoxycoformycin was proven to have an inhibitory effect on pain transmission (Poon and Sawynok, 1999), and Fujisawa Pharmaceuticals claim adenosine deaminase inhibitors to be active against chronic pain. 

At a much later date, evidence supporting this assumption came from enzymic studies, which indicated that the deoxypentosyl residues of all nucleosides of deoxyribonucleic acids are similar. Manson and Lampen67 demonstrated that deoxyinosine (IX)68 69 can be synthesized from thy-... 

Deoxyinosine is not considered to be a normal constituent of deoxyribonucleic acid. Deaminases are present in deoxyribonucleic acid which convert (see Ref. 69) deoxyadenosine to IX. Earlier methods for isolation of the nucleosides of deoxyribonucleic acid usually yielded the hypoxanthine (6-hydroxypurine) nucleoside instead of deoxyadenosine. 

A close look at this reaction reveals that in the opposite direction, the reaction is of the phosphorolysis type. For this reason, the enzymes catalyzing the reaction with ribose-l-phosphate are called phosphorylases, and they also participate in nucleic acid degradation pathways. Purine nucleoside phosphorylases thus convert hypoxanthine and guanine to either inosine and guanosine if ribose-l-phosphate is the substrate or to deoxyinosine and deoxyguanosine if deoxyribose-1-phosphate is the substrate. Uridine phosphorylase converts uracil to uridine in the presence of ribose-l-phosphate, and thymidine is formed from thymine and deoxyribose-l-phosphate through the action of thymidine phosphorylase. 

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