Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.17 (adenosine deaminase)
 5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A facile synthesis of oligodeoxynucleotides (ODN) containing 2'-deoxy-6-thioinosine (dI6S) based on the convertible nucleoside O6-phenyl-2'-deoxyinosine is presented. After standard solid-phase DNA synthesis and removal of the cyanoethyl protecting groups with DBU treatment with aqueous sodium hydrogen sulfide introduces the sulfur functionality, deprotects the other nucleobases and cleaves the ODN from the solid support in a one-pot reaction. In addition, the extinction coefficient of 2'-deoxy-6-thioinosine is determined by enzymatic fragmentation of the resulting ODN in the presence of adenosine deaminase.
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PMID:Convenient synthesis of oligodeoxynucleotides containing 2'-deoxy-6-thioinosine. 1456 42

To evaluate if endogenous extracellular adenosine influences sodium channel activity in nerve terminals, we investigated how manipulations of extracellular adenosine levels influence 22Na uptake by rat brain synaptosomes stimulated with veratridine (VT). To decrease extracellular adenosine levels, adenosine deaminase (ADA) that converts adenosine into an inactive metabolite was used. To increase extracellular adenosine levels, we used the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), as well as the inhibitor of adenosine transport, nitrobenzylthioinosine (NBTI). ADA (0.1-5 U/ml) caused an excitatory effect on 22Na uptake stimulated by veratridine, which was abolished in the presence of the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA, 25 microM). Both the adenosine uptake inhibitor nitrobenzylthioinosine (NBTI, 1-10 microM) and the adenosine deaminase inhibitor EHNA (10-25 microM) inhibited 22Na uptake by rat brain synaptosomes. It is suggested that adenosine is tonically inhibiting sodium uptake by rat brain synaptosomes.
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PMID:Endogenous adenosine modulation of 22Na uptake by rat brain synaptosomes. 1457 Apr 5

The kinetic parameters of adenosine deaminase such as Km and Ki were determined in the absence and presence of adenine derivatives (R1-R24) in sodium phosphate buffer (50 mM; pH 7.5) solution at 27 degrees C. These kinetic parameters were used for QSAR analysis. As such, we found some theoretical descriptors to which the binding affinity of adenosine deaminase (ADA) towards several adenine nucleosides as inhibitors is correlated. QSAR analysis has revealed that binding affinity of the adenine nucleosides upon interaction with ADA depends on the molecular volume, dipole moment of the molecule, electric charge around the N1 atom, and the highest of positive charge for the related molecules.
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PMID:QSAR analysis for ADA upon interaction with a series of adenine derivatives as inhibitors. 1511 27

Kinetic and thermodynamic studies have been made on the effect of acetaminophen on the activity and structure of adenosine deaminase in 50 mM sodium phosphate buffer pH 7.5, at two temperatures of 27 and 37 degrees C using UV spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. Acetaminophen acts as a competitive inhibitor at 27 degrees C (Ki = 126 microM) and an uncompetitive inhibitor at 37 degrees C (Ki = 214 microM). Circular dichroism studies do not show any considerable effect on the secondary structure of adenosine deaminase by increasing the temperature from 27 to 37 degrees C. However, the secondary structure of the protein becomes more compact at 37 degrees C in the presence of acetaminophen. Fluorescence spectroscopy studies show considerable change in the tertiary structure of the protein by increasing the temperature from 27 to 37 degrees C. Also, the fluorescence spectrum of the protein incubated with different concentrations of acetaminophen show different inhibition behaviors by the effector at the two temperatures.
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PMID:Kinetic and structural analysis of the inhibition of adenosine deaminase by acetaminophen. 1520 96

Thermodynamic studies were carried out to evaluate the binding of theophylline on adenosine deaminase (ADA) in 50 mM sodium phosphate buffer pH 7.5, at 300 K, using isothermal titration calorimetry (ITC). A simple method for determination of binding isotherm in the drug--ADA interaction was applied using ITC data. ADA has two binding sites for theophylline, which show positive cooperativity in its sites. The intrinsic association equilibrium constants are 6 and 52 mM(-1) in the first and second binding sites, respectively. Hence, occupation of the first site has produced an appreciable enhancement by 8.7 of the binding affinity of the second site. The molar enthalpies of binding are -12.2 and -14.9 kJ/mol in the first and second binding sites, respectively.
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PMID:Binding properties of adenosine deaminase interacted with theophylline. 1546 30

This longitudinal study was conducted in BP Koirala Institute of Health Sciences (BPKIHS), a Medical University situated in eastern Nepal, between May 2001 and December 2001. The main objective of the study was to identify the role of adenosine deaminase (ADA) activity in patients with visceral leishmaniasis (VL) for management. There was a significant increase in mean ADA activity in sera of 49 patients with VL (323.71+/-184.51 IU/L) compared with 50 samples of control groups (47.11+/-24.94 IU/L) from the same endemic area (P < 0.001). ADA activities were found to be significantly decreased (50.35+/-41.35 IU/L) in follow-up cases (n = 19) after 30 days with sodium stibogluconate treatment at a dose of 20 mg/kg/day intramuscularly. The fall in the level of ADAF (after treatment) in follow-up cases correlated with the cure of disease, as evident from improvement of vital signs and symptoms and the absence of Leishmania donavani bodies in the sera. The study therefore suggests the possibility of using human serum ADA as a convenient marker to evaluate the diagnosis of VL to support the clinical findings, especially in those settings where there is a lack of highly qualified personnel and diagnostic facilities.
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PMID:Adenosine deaminase activity in sera of patients with visceral leishmaniasis in Nepal. 1597 28

The effects of paeoniflorin, a glycoside isolated from the root of Paeonia lactiflora, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15 were investigated. Paeoniflorin (1-300 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Paeoniflorin caused no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of paeoniflorin-induced inhibition of I(Ca,L) was 14 microM. However, neither adenosine deaminase (1 U/ml) nor 8-cyclopentyl-1, 3-dipropylxanthine (10 microM) could reverse the inhibition by paeoniflorin of I(Ca,L). Paeoniflorin (30 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -10 mV. It also prolonged the recovery of I(Ca,L). The inhibitory effect of paeoniflorin on I(Ca,L) exhibited tonic and use-dependent characteristics. Paeoniflorin could effectively suppress I(Ca,L) evoked by action potential waveforms. Paeoniflorin at a concentration of 30 microM produce a slight inhibition of voltage-dependent Na+ current and delayed rectifier K+ current. Under current-clamp configuration, unlike adenosine, this compound decreased the firing of action potentials. Taken together, this study indicates that paeoniflorin can block L-type Ca2+ channels in NG108-15 cells in a mechanism unlinked to the binding to adenosine receptors. The effects of paeoniflorin on ion currents may partly, if not entirely, contribute to the underlying mechanisms through which it affects neuronal or neuroendocrine function.
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PMID:Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. 1624 10

Oxanosine 3r, 5-amino-3-beta-(d-ribofuranosyl)-3H-imidazo[4,5-d][1,3]oxazine-7-one, was isolated as a novel nucleoside antibiotic in 1981 from Streptomyces capreolus MG265-CF3. Oxanosine became relevant in toxicology in 1996 with the discovery that it is formed in nitrosative guanosine deamination. As part of studies of the mechanism of oxanosine formation, the synthesis was attempted of [7- 18O]oxanosine by enzymatic 16O/18O-exchange with adenosine deaminase (ADA) in analogy to the synthesis of [6- 18O]guanosine from 2-amino-6-chloropurine. Unexpectedly, it was discovered that the incubation of oxanosine 3r with ADA in sodium phosphate buffer (pH = 7.4) results in 1-beta-(d-ribofuranosyl)-5-ureido-1H-imidazole-4-carboxylic acid 4r. The reaction of the 2'-deoxyribose derivative 3d forms 4d in analogy. The reaction products were separated by preparative RP-HPLC and characterized by LC/MS and MS/MS analyses and UV/vis and NMR spectroscopy, and NMR assignments were corroborated by GIAO and GIAO-PCM calculations. Reaction in H2 18O leads to 18O-incorporation at C7. The hydrolysis of 3 to 4 can be rationalized on the basis of the known mode of action of ADA, and an explanation is provided for ADA's accomplishment of the "usual" substitution at C6 of adenosine (addition to the exocyclic bond) and the "lactone hydrolysis" of oxanosine (addition to the endocyclic double bond). The Michaelis-Menten constant of Km = 1.0 (+/-0.2) mM was measured for oxanosine. Implications are discussed for studies of nitrosative deamination of nucleosides, nucleotides, and oligonucleotides.
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PMID:Oxanosine is a substrate of adenosine deaminase. Implications for the quest for a toxicological marker for nitrosation activity. 1635 73

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.
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PMID:Biomarkers of acute renal injury and renal failure. 1691 49

Pentostatin is an adenosine deaminase inhibitor used in the treatment of hairy cell leukemia and T-cell lymphomas. A 27-year-old man with refractory cutaneous T-cell lymphoma developed severe hyponatremia 3 days after completing his first cycle of pentostatin therapy. Shortly after hospital admission, he became disoriented and was admitted to the medical intensive care unit and treated with a combination of hypertonic saline, intravenous diuretics, and fluid restriction to reestablish normal sodium homeostasis. The mechanism by which pentostatin may have induced hyponatremia in this patient is unknown; clinical and laboratory findings represented both extrarenal sodium loss and syndrome of inappropriate antidiuretic hormone. Clinicians should be aware of the possible development of life-threatening symptomatic hyponatremia in patients receiving pentostatin.
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PMID:Possible pentostatin-induced symptomatic hyponatremia. 1719 71


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