Adenosine deaminase, activity

Acid-catalyzed matrices, kinetics of controlled release, 170-179 Active targeting, definition, 276 Adenosine deaminase, activity of polyethylene glycol modified enzymes, 98-99 Adjuvax... 

F9. Fujii, H., Miwa, S., Tani, K., Fujinami, N., and Asano, H., Overproduction of structurally normal enzyme in man Hereditary hemolytic anemia with increased red cell adenosine deaminase activity. Br. J. Haematol. 51,427-430 (1982). 

Singhal D, Ho NF and Anderson BD (1998) Absorption and Intestinal Metabolism of Purine Dideoxynucleosides and an Adenosine Deaminase-Activated Prodrug of 2/,3/-Dideoxyinosine in the Mesenteric Vein Cannulated Rat Ileum. J Pharm Sci 87 pp 569-577. 

H. Ford, M. Siddiqui, J.S. Driscoll, V.E. Marquez, J.A. Kelley, H. Mitsuya, T. Shirasaka, Lipophilic, acid-stable, adenosine deaminase-activated anti-HIV prodrugs for central nervous system delivery. 2. 6-Halo- and 6-alkoxy prodrugs of 2 -.beta.-fluoro-2, 3 -dideoxyinosine, J. Med. Chem. 38 (1995) 1189-1195. 

Pharmacokinetics Pegademase bovine is rapidly absorbed following intramuscular administration of Adagen, plasma adenosine deaminase activity generally normalizes after 2 to 3 weeks of weekly intramuscular injections. The half-life of pegademase is 48 to 72 hours. 

Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. Zavialov, A.V., Engstrom, A. (2005). Biochem J, 391, 51-57. 

Hog spleen acid DNase, as obtained by the above procedure, is completely free of contaminating phosphatase, exonuclease, and adenosine deaminase activities. The enzyme has a weak intrinsic hydrolytic activity on bis(p-nitrophenyl) phosphate and the p-nitrophenyl derivatives of deoxyribonucleoside 3 -phosphates (see Section III,D,3). 

The enzyme obtained by this purification procedure 11), when tested for contaminants under very stringent conditions, was found to be completely free from phosphatase, DNase, ribonuclease, and adenosine deaminase activities. 

Elgun S, Keskinege A, Kumbasar H (1999) Dipeptidyl peptidase IV and adenosine deaminase activity. Decrease in depression. Psychoneuroendocrinology 24 823-832... 

Nucleosides in Scheme 54 were evaluated for cytotoxicity, adenosine deaminase activity (83JMC1483), and activity against hepatitis B virus (91EUP409227). 

Johnson, M. D., Chen, J. and Anderson, B. D. (2002) Investigation of the mechanism of enhancement of central nervous system delivery of 2 -P-fluoro-2, 3 -dideoxyinosine via a blood-brain barrier adenosine deaminase-activated prodrug. Drug Metab. Dispos., 30, 191-198. 

Adenosine deaminase (ADA EC 3.5.4.4) is the enzyme of the purine metabolism that deaminates adenosine and l deoxyadenosme to inosine and 2 -deoxymosine, respectively. ADA deficiency, which leads to severe combined immunodeficiency disease (SCID), is associated with a decrease in RBC adenosine deaminase activity, without hemolysis. ADA deficiency will not be discussed here. 

Chottiner EG, Cloft HJ, Tartaglia AP, Mitchell BS. Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis. J Clin Invest 1987 79 1001-5. 

Loss of Adenosine Deaminase Activity Results in Severe... 

A deficiency in adenosine deaminase activity is associated with some forms of severe combined immunodeficiency (8CTD), an immunological disorder. Persons with the disorder have severe recurring infections, often leading to death at an early age. SCID is characterized by a loss of T cells, are crucial to the immune response (Section 33.5), Although the biochemical basis of the disorder is not clearly established, a lack of adenosine... 

Few detailed studies have been done on the purine salvage enzymes of procyclic African trypanosomes. Tb. gambiense has high levels of guanine deaminase and lacks adenine and adenosine deaminase activities (8). Tb. brucei, T.b. gambiense and T.b. rhodesiense convert allopurinol into aminopyrazolopyrimidine nucleotides and incorporates these into RNA (49). This indicates that HPRTase, succino-AMP synthetase, and succino-AMP lyase are present. At least three nucleoside cleavage activities are present (Berens, unpublished results) two are hydrolases, of which one is specific for purine ribonucleosides and the other is specific for purine deoxyribonucleosides. The third nucleoside cleavage activity is a methylthioadenosine/adenosine phosphorylase. The adenosine kinase is similar to that of L. donovani (Berens, unpublished results). 

In rat heart the control rate of adenylate deaminase activity was lower, and that of adenylate dephosphorylation higher than in lung. Most of the ammonia formed from adenylate was therefore due to adenosine deaminase activity. ATP stimulated adenylate deaminase to almost the same relative degree in heart as in lung, but due to a marked inhibition of dephosphorylation the total amoimt of ammonia formed was less in heart. These data also raise questions concerning the identity and substrate specificities of the enzyme(s) that dephosphorylate adenylate and inosinate. 

Adenosine deaminase (adenosine aminohydro-lase EC 3.5.4.4) catalyses the deamination of adenosine and deoxyadenosine. Thioglycollate-stimulated C57BL/6 mouse peritoneal macrophages contained high levels of adenosine deaminase activity (Chan 1979). In the presence of deoxycoformy-cin (1 pg/ml), a potent inhibitor of adenosine deaminase (Agarwal et al. 1977), thioglycoUate-stimulated mouse peritoneal macrophages excreted deoxyadenosine (Chan 1979). 

Mammalian tissues do not contain adenine deaminase, but specific enzymes able to deaminate adenosine and 5 -adenylic acid have been found in a variety of mammals. Adenosine deaminase activity has been detected in intestine, liver, spleen, brain, kidney, heart, and skeletal muscle. Adenosine deaminase has been partially purified from the intestinal mucosa. The enzyme has a great affinity for adenosine and deoxyadenosine and only low affinity for 2 -AMP and 3, 3 -cyclic AMP. Its activity is lost on dialysis. The enzyme acts optimally at pH 7. 

Human amniotic cells were considered as an alternative source of enzyme replacement. They do not express HLA antigens or microglobulin and consequently are not rejected when transplanted (5) They secrete many lysosomal storage enzymes and in addition appear to express significant adenosine deaminase activity. However, very little immune function was restored in S.Y. and none at all in K.A. after enzyme replacement therapy by red cell transfusions, and it was thought unlikely that they would have provided any further benefit. All three children have... 

Adenosine deaminase activity was determined using a modification of the spectrophotometric method of uric acid production as previously described (Cowan et al., 1982). 

At regular intervals the immune status of the patient was assessed as well as the serum content and the urinary excretion of purine- and pyrimidine metabolites according to methods described in detail previously (6,8,10). The (deoxy)ribonucleotide content of the erythrocytes was analyzed by HPLC Ul)- Perchloric acid extracts of freshly withdrawn blood were made according to Cohen et al. (2) with minor modifications. In order to analyze deoxyribo-nucleotides the neutralized perchloric acid extracts were treated with sodium periodate according to Garret and Santi (12). 2,3 Di-phosphoglycerate (2,3-DPG) in the erythrocytes was determined as previously described (13). Ecto-5 -nucleotidase on intact lymphocytes was determined as described(14). Adenosine deaminase activity of the lymphocytes was determined essentially according to van Laar-hoven et al. (15). 

It was, therefore, of interest to determine whether specific inhibition of adenosine deaminase activity vivo using the tight binding inhibitor, 2 -deoxycoformycin, interferred with the malaria parasites IE growth and development. 

Table 1 Adenosine Deaminase Activity in Malaria ( . Knowlesi) Infected Erythrocytes of Rhesus Monkeys...

Condition Adenosine deaminase activity (nanomoles/mln/mg. protein)... 

Uberti, J., Johnson, R.M., Talley, R., and Lightbody, J.J., 1976, Decreased lymphocyte adenosine deaminase activity in tumor patients. Cancer Res., 36 2046. 

R. Hirschhorn, Adenosine deaminase activity in chronic lymphocytic leukemia. Relationship to B- and T-cell subpopulations. J.Clin. Invest. 57 756 (1976). 

Fig. 1. Synthesis of 9-(p-bromoacetamidobenzyl)adenine, aflSnity labeling of lysine in adenosine deaminase active site, and acid hydrolysis of reagent amide bond (dotted line) to produce carboxymethylamino acids.

Adenosine deaminase (0.5-200 itM), purified from calf intestinal mucosa, in 0.2 M sodium phosphate at pH 8, containing 10% dimethyl sulfoxide (v/v), is treated at 37° in the dark with 9-(p-bromoacetamido-benzyl) adenine (0.01-5 mAf). The alkylating reagent is added dissolved in dimethyl sulfoxide. When necessary, the pH of the reaction mixture is maintained constant by addition of 1.0 A NaOH. At intervals 5-10 / samples are removed and diluted in 0.1 M sodium phosphate at pH 7.5 adenosine deaminase activity is measured. The enzyme activity is determined by the method of Kalckar with adenosine as substrate by following the decrease in absorbance at 265 nm in 0.1 Af sodium phosphate at pH 7.5. 

The hydrophobic portion of the reagent, but not adenine, appears to be essential for the alkylation of the adenosine deaminase active site since benzylbromoacetate irreversibly inactivates the enzyme whereas the site is inaccessible to haloacetate and its amide. Benzylbromoacetate and 9-(p-bromoacetamidobenzyl) adenine are only 4 and 2.5 more reactive, respectively, than bromoacetate toward 4-(p-nitrobenzyl)pyridine. The oxidation of ribose of purine riboside with periodic acid in order to produce carbonyl groups that may react with lysine residue destroys the inhibitory effectiveness of the nucleoside. ... 

Belle LP, Bitencourt PER, Abdalla FH, Bona KS de, Peres A, Maders LDK, Moretto MB (2013) Aqueous seed extract of Syzygium cumini inhibits the dipeptidyl peptidase IV and adenosine deaminase activities, but it does not change the CD26 expression in lymphocytes in vitro. J Physiol Biochem 69 119-124... 

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