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

5 serum protein polymorphic systems (haptoglobin, alkaline phosphatase, group-specific (Gc) proteins, beta2-glycoprotein 1 and leucine aminopeptidase) and 6 red-cell polymorphisms (adenosine deaminase, adenylate kinase, phosphoglucomutase, glutamic-pyruvic transaminase, phosphogluconate dehydrogenase and acid phosphatase) have been investigated in 54 subjects with tuberous sclerosis. The frequencies of all systems were compared with those of a control sample drawn from a similar mentally retarded population and abnormal distributions were detected in the haptoglobin and Gc system. Quantitative estimation of the serum levels of the Gc protein failed to detect any inter-group differences. Data on the deviations from the Hardy-Weinberg equlibrium, Haldane's Log ratio test between groups, and gene frequencies of both test and control groups are given. It is suggested that selection by mortality is the possible causation for the abnormal distribution of the Gc phenotypes, but the haptoglobin phenotype distribution requires further investigation with care being taken in the selection of control subjects.
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PMID:Serum and tissue proteins in tuberous sclerosis. I. Serum and red-cell polymorphic systems. 16 11

Concanavalin A inhibits serum 5'-nucleotidase activity, without causing significant inhibition of alkaline phosphatase activity. This observation serves as the basis for a new method for assaying the 5'-nucleotidase activity in serum, which depends upon the difference between the enzymic hydrolysis of adenosine-5'-monophosphate in the presence and absence of concanavalin A. A denosine released by the 5'-nucleotidase reaction is deaminated by a coupled reaction with adenosine deaminase to liberate inosine and ammonia, and ammonia is measured colorimetrically by the Berthelot reaction. In sera from 40 healthy adult persons, 5'-nucleotidase activity averaged 6.4 U/liter (SD, +/-2.0; range, 3-12). In sera from 100 patients, measurements of 5'-nucleotidase activity by the new assay averaged 8% lower than by a generally accepted method in which phenyl phosphate is used to suppress hydrolysis of adenosine-5'-monophosphate by alkaline phosphatase activity. The clinical validy of the new assay was tested by measuring serum 5'-nucleotidase activities in rats with bile duct ligation and in rats treated with thioacetamide to induce hepatocellular injury.
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PMID:Inhibition by concanavalin A as the basis for a specific assay of serum 5'-nucleotidase activity. 92 81

Saturation and inhibition kinetics data for rat liver ADP-ribose pyrophosphatase (EC 3.6.1.13) were obtained from progress curves initiated by the addition of substrate and recorded spectrophotometrically until the end point was reached. The hydrolysis of ADP-ribose was coupled to either alkaline phosphatase and adenosine deaminase or AMP deaminase. The validity of the approach was shown because: (i) the coupled hydrolysis of ADP-ribose was essentially irreversible; (ii) ADP-ribose pyrophosphate was stable at 37 degrees C in the conditions needed for the assay; and (iii) accumulated reaction products did not inhibit detectably in the conditions of the assay. In addition, several identical progress curves could be successively recorded by repetition of the addition of substrate. In that way it was possible to carry out complete inhibition studies by increasing the inhibitor concentration between successive substrate additions. Studying the inhibition by high D-ribose concentrations, meaningful results could be obtained at four different inhibitor concentrations in a single reaction mixture, which represented a great saving of enzyme preparation with respect to what would be needed in an equivalent initial rate study.
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PMID:Enzyme saturation and inhibition kinetics studied from multiple progress curves recorded spectrophotometrically from single reaction mixtures for ADP-ribose pyrophosphatase. 164 14

A potentiometric immunosensor for the detection of human IgG has been developed using an asymmetric, ion-selective membrane with immobilized adenosine deaminase and IgG. A protein A-alkaline phosphatase conjugate binds to the immobilized IgG, creating a bienzymatic catalytic layer. In the presence of sample IgG, the conjugate does not bind to the membrane. Instead, the intermediate in the two-step reaction (adenosine) must diffuse to the membrane surface, reducing the rate of product (ammonium) formation within the diffusion layer detected by the membrane. The immunosensor demonstrated is for the determination of IgG. A simplified model is described to predict the maximum rate enhancement for the 'channeled' versus 'unchanneled' reaction mechanisms.
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PMID:Potentiometric enzyme channeling immunosensor for proteins. 175 3

A new method for the determination of adenine phosphoribosyltransferase (APRT) activity in human erythrocytes is described. APRT activity was assayed by a non-radiochemical method in which adenosine monophosphate (AMP) and AMP metabolites produced from a substrate adenine were converted to inosine by alkaline phosphatase and adenosine deaminase. The inosine thus produced was quantitated by reversed phase HPLC. This method was simple, precise, sensitive and free from interference with other co-existing erythrocyte enzymes. Four patients with 2,8-dihydroxyadenine urolithiasis and others with several disorders in purine metabolism have been studied, showing that the present method is clinically useful for the diagnosis and the evaluation of the severity of some human diseases.
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PMID:A new method for the determination of adenine phosphoribosyltransferase activity in human erythrocytes by reversed phase high performance liquid chromatography. 186 58

Using histochemical detection, we have visualized in situ the complete metabolic pathway for the degradation of purine nucleotides. From the tongue to the ileum, diverse epithelial cell types lining the lumen of the mouse gastrointestinal (GI) tract strongly coexpress each of the five key purine catabolic enzymes. Dramatic increases in the expression of each enzyme occurred during postnatal maturation of the GI tract. Using in situ hybridization, an intense accumulation of adenosine deaminase (ADA) mRNA was detected only within GI epithelial cells undergoing postmitotic differentiation. In a similar manner, at the developing maternal-fetal interface, high level expression of the purine catabolic pathway also occurred in a unique subset of maternal decidual cells previously known to express high levels of alkaline phosphatase and ADA. This induction occurred almost immediately after implantation in the periembryonic maternal decidual cells, shortly thereafter in antimesometrial decidual cells, and later in cells of the placental decidua basalis: all of which contain cell types thought to be undergoing programmed cell death. The expression of the pathway at the site of embryo implantation appears to be critical because its pharmacologic inhibition during pregnancy has been found to be embryolethal or teratogenic. Purine destruction at these nutritional interfaces (placenta and gastrointestinal tract) seem to override any potential economy of purine salvage, and may represent biochemical adaptation to nucleic acid breakdown occurring in the context of dietary digestion or extensive programmed cell death.
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PMID:Coordinate developmental regulation of purine catabolic enzyme expression in gastrointestinal and postimplantation reproductive tracts. 191 35

The enzymatic pattern of five enzymes involved in the purine salvage pathway, namely purine nucleoside phosphorylase (EC 2.4.2.1), adenosine deaminase (EC 3.5.4.4), 5'-nucleotidase (EC 3.1.3.5), alkaline phosphatase (EC 3.1.3.1), and hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) has been evaluated both in human intestinal and breast carcinomas and compared to that of normal tissues. A higher level of hypoxanthine-guanine phosphoribosyltransferase was associated with tumor tissues. This metabolic alteration should lead to an elevated synthesis of nucleotides in cancer cells, might confer selective growth advantages to neoplastic tissues, and account, at least in part, for the difficulties encountered in the chemotherapy of human tumors, by using compounds affecting only the purine de novo biosynthesis.
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PMID:Purine salvage enzyme activities in normal and neoplastic human tissues. 212 39

Neplanocin A is a naturally occurring carbocyclic analog of adenosine which contains a cyclopentene moiety in place of ribose and has demonstrated antitumor and antimicrobial activity. This compound was highly toxic to Chinese hamster ovary (CHO) cells; the approximate minimum inhibitory concentration of neplanocin A for inhibition of clone formation was 0.1 microM. The toxicity of the agent was greatly reduced by prior treatment with adenosine deaminase. [3H]Uridine incorporation into perchloric acid insoluble material in growing cells was inhibited by neplanocin A more dramatically than that of [3H]thymidine or [3H]leucine. Treatment with the drug resulted in a marked depression of ATP pool levels. High pressure liquid chromatographic analysis of cellular nucleotide pools from cells treated with neplanocin A revealed the formation of an apparent drug metabolite (NpcTP) that eluted in the triphosphate region of the chromatographic profile. Treatment of NpcTP with alkaline phosphatase produced a nucleoside with properties similar to neplanocin A. An adenosine-kinase-deficient cell line formed little, if any, NpcTP but demonstrated only slight resistance to the agent. These observations suggest that neplanocin A was efficiently metabolized to the triphosphate level but that this metabolite was responsible for only a fraction of the observed toxicity.
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PMID:Metabolism and action of neplanocin A in Chinese hamster ovary cells. 240 84

9-[5'-(2-Oxo-1,3,2-oxazaphosphorinan-2-yl)-beta-D-arabinosyl]adeni ne (1c) and 9-[5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-beta-D-arabinosyl]adeni ne (1d) were synthesized by reaction of 9-[beta-D-arabinofuranosyl]adenine with phosphoryl chloride with 1-amino-3-propanol and 1,3-propanediol, respectively. 1c consisted of a mixture of diastereomers, while 1d was enantiomerically homogeneous. The structures of these compounds were established by spectral (1H NMR, MS, UV) and elemental analyses. Both 1c and 1d were resistant to degradation by 5'-nucleotidase, alkaline phosphatase, venom phosphodiesterase, crude snake venom, adenosine deaminase, and adenylate deaminase. Neither compound was significantly biotransformed by mouse hepatic microsomal preparations in the presence of an NADPH-generating system. Compound 1c was marginally effective at prolonging the life span of mice bearing P-388 leukemia; compound 1d, however, was inactive.
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PMID:Synthesis and biological evaluation of 9-[5'-(2-oxo-1,3,2-oxazaphosphorinan-2-yl)-beta-D-arabinosyl]ade nine and 9-[5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-beta-D-arabinosyl]ade nine: potential neutral precursors of 9-[beta-D-arabinofuranosyl]adenine 5'-monophosphate. 241 27

Fludarabine (9-beta-D-arabinofuranosyl 2-fluoro-adenine monophosphate) is a fluorinated analogue of adenine which is relatively resistant to deamination by adenosine deaminase. Phase I clinical trials disclosed significant antitumor activity in lymphoid malignancies. Fludarabine has been used in the treatment of CLL since March, 1985, at a dose of 25-30 mg/m2/day x 5 days each 3-4 weeks by short intravenous infusion. Sixty-eight previously treated patients with CLL are evaluable for response. The median age was 60 years, 50 were male the median number of prior chemotherapy regimens was 2, and the median time from initial chemotherapy to fludarabine was 45 months. Forty-three (63%) were Rai stages 3 and 4, 31 (46%) were Binet Stage C. Twenty patients (29%) obtained a complete remission (CR), defined as peripheral lymphocytes less than 4,000/microliters, no clinical evidence of disease, less than 30% of lymphocytes in the bone marrow (with no residual nodules), or a nodular partial remission, NPR (CR except for residual lymphoid nodules), and 19 (28%) a partial remission (less than 50% reduction in tumor in nodes, liver, spleen and bone marrow and greater than 1 log reduction in the lymphocyte count). The complete remission rate for the various involved sites were blood (69%), liver (52%), spleen (55%), and nodes (48%). The bone marrow was the least responsive site with 16% CR and 44% PR. The number of prior regimens did not have a significant response rate or survival. The serum albumin , alkaline phosphatase, platelet and hemoglobin level all were associated with survival from the start of fludarabine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fludarabine therapy in chronic lymphocytic leukemia (CLL). 246 94


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