A study on the inhibition of adenosine deaminase

Alunni, Sergio; Orrù, Mara; Ottavi, Laura

doi:10.1080/14756360701475233

Cited by 16 publications

(11 citation statements)

References 37 publications

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“…With UV-Vis, absorption peaks are tracked, either for the product inosine at 235 nm or the substrate adenosine at 260 nm. 6 However, high sample turbidity or optical density can cause interference and many adenosine deaminase inhibitors have absorbance properties similar to adenosine and inosine. 6 Furthermore, because adenosine and inosine have similar absorption bands, chromatographic separation may be necessary to isolate them in a mixture.…”

Section: Introductionmentioning

confidence: 99%

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry

Venton

2010

Phys. Chem. Chem. Phys.

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Adenosine deaminase is an enzyme involved in purine metabolism and its inhibitors are used as anticancer and antiviral drugs. In this study, we show that fast-scan cyclic voltammetry at carbon-fiber microelectrodes can be used to study the kinetics of adenosine deaminase by electrochemically monitoring decreases in adenosine concentration. Buffer and salt concentrations were shown to affect the enzyme kinetics and the inhibition by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and deoxycoformycin (DCF). In a Tris buffer containing salts that mimic cerebrospinal fluid, EHNA and DCF showed non-competitive inhibition with a K(i) of 1.7 +/- 0.6 nM and 1.2 +/- 0.2 nM, respectively. However, removing the divalent cations from the Tris buffer caused the inhibition to be competitive and reduced the K(i) for DCF by two orders of magnitude. In phosphate-buffered saline, the K(i) was 1.0 +/- 0.2 nM for EHNA and 3.6 +/- 0.3 pM for DCF, similar to literature values. Adenosine deaminase was also competitively inhibited by AgNO(3), showing it is susceptible to silver toxicity. Caffeine was found to increase adenosine deaminase activity. This is a fast, easy method for screening drug effects on enzyme kinetics and could be applied to other enzymatic reactions where there is a significant difference in the electroactivity of the reactant and product.

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Section: Introductionmentioning

confidence: 99%

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry

Venton

2010

Phys. Chem. Chem. Phys.

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“…Because of the importance of excess ADA in pathology, inhibitors of ADA may have potential clinical applications. 43 To demonstrate the feasibility of this method for screening ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), a well-known inhibitor of ADA, was selected as a model inhibitor for this study. 35 Fig.…”

Section: Inhibition Of the Ada Activitymentioning

confidence: 99%

A gold nanoparticle-based label free colorimetric aptasensor for adenosine deaminase detection and inhibition assay

Cheng

Xing

et al. 2015

Analyst

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A novel strategy for the fabrication of a colorimetric aptasensor using label free gold nanoparticles (AuNPs) is proposed in this work, and the strategy has been employed for the assay of adenosine deaminase (ADA) activity. The aptasensor consists of adenosine (AD) aptamer, AD and AuNPs. The design of the biosensor takes advantage of the special optical properties of AuNPs and the interaction between AuNPs and single-strand DNA. In the absence of ADA, the AuNPs are aggregated and are blue in color under appropriate salt concentration because of the grid structure of an AD aptamer when binding to AD, while in the presence of the analyte, AuNPs remain dispersed with red color under the same concentration of salt owing to ADA converting AD into inosine which has no affinity with the AD aptamer, thus allowing quantitative investigation of ADA activity. The present strategy is simple, cost-effective, selective and sensitive for ADA with a detection limit of 1.526 U L(-1), which is about one order of magnitude lower than that previously reported. In addition, a very low concentration of the inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) could generate a distinguishable response. Therefore, the AuNP-based colorimetric biosensor has great potential in the diagnosis of ADA-relevant diseases and drug screening.

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“…Upon uptake into cells, adenosine can be metabolized by intracellular ADA and/or adenosine kinase (AK). 6,7 Adenosine also reacts with homocysteine (HC) to generate S-adenosyl-L-homocysteine (SAH). 6 SAH is a product of S-adenosyl-L-methionine (SAM) de-methylation.…”

Section: Introductionmentioning

confidence: 99%

Sustained adenosine exposure causes endothelial mitochondrial dysfunction via equilibrative nucleoside transporters

Rounds

Lü

2020

Pulm. circ.

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Adenosine is a potent signaling molecule that has paradoxical effects on lung diseases. We have previously demonstrated that sustained adenosine exposure by inhibition of adenosine degradation impairs lung endothelial barrier integrity and causes intrinsic apoptosis through equilibrative nucleoside transporter1/2-mediated intracellular adenosine signaling. In this study, we further demonstrated that sustained adenosine exposure increased mitochondrial reactive oxygen species and reduced mitochondrial respiration via equilibrative nucleoside transporter1/2, but not via adenosine receptor-mediated signaling. We have previously shown that sustained adenosine exposure activates p38 and c-Jun N-terminal kinases in mitochondria. Here, we show that activation of p38 and JNK partially contributed to sustained adenosine-induced mitochondrial reactive oxygen species production. We also found that sustained adenosine exposure promoted mitochondrial fission and increased mitophagy. Finally, mitochondria-targeted antioxidants prevented sustained adenosine exposure-induced mitochondrial fission and improved cell survival. Our results suggest that inhibition of equilibrative nucleoside transporter1/2 and mitochondria-targeted antioxidants may be potential therapeutic approaches for lung diseases associated with sustained elevated adenosine.

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A study on the inhibition of adenosine deaminase

Cited by 16 publications

References 37 publications

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry

A gold nanoparticle-based label free colorimetric aptasensor for adenosine deaminase detection and inhibition assay

Sustained adenosine exposure causes endothelial mitochondrial dysfunction via equilibrative nucleoside transporters

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