Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1) The rate of 2,3-bisphosphoglycerate breakdown is independent of pH value. 2) The adenine nucleotide pattern at alkaline pH values with its characteristic lowering of ATP and the accompanying accumulation of fructose-1,6-bisphosphate is caused by a relative excess of the activity of the hexokinase-phosphofructokinase system as compared wity pyruvate kinase. 3) The breakdown of adenine nucleotides proceeds via AMP mainly through phosphatase and not via AMP deaminase. 4) The constancy of the sum of nucleotides as long as glucose is present is postulated to be due to resynthesis via adenosine kinase which competes successfully with adenosine deaminase. 5) A procedure is given to calculate ATPase activity of glucose-depleted red cells. The results indicate that the ATPase activity is less at lower pH values and declines with time. An ATPase with a high Km for ATP is postulated. 6) During glucose depletion ATP production is mostly derived from the breakdown of 2,3-bisphosphoglycerate and the supply from the pentose phosphate pool both of which proceed at a constant rate. The contribution of pentose phosphate from the breakdown of adenine nucleotides amounts to 40% of the lactate formed at pH 6.8 and is about twice the lactate at pH 8.1.
 ...
PMID:The breakdown of adenine nucleotides in glucose-depleted human red cells. 4 52

The activity of myocardial adenosine kinase (E.N. 2.7.1.20) in a number of species was assayed. Rat heart contained the highest specific activity. From this source adenosine kinase was purified in a simple way 80-fold, until it was free of adenosine deaminase activity. A molecular weight of about 39 000 was measured. NSC 113939 (1), NSC 113940 and 8-azaadenosine inhibited myocardial adenosine kinase. Dipyridamole stimulated the enzyme at high adenosine levels, and inhibited at low substrate concentrations. A number of divalent cations could (partially) substitute for Mg2+. The optimal concentration of MgCl2 or MnCl2 was about 0.5 mM; concentrations exceeding 1 mM inhibited severely. An apparent Km for ATP of 0.1 mM was measured, whereas an apparent Km for adenosine of 0.5 muM was was found. The latter increased to 3.3 muM, when dipyridamole was added. Replacement of ATP by GTB or ITP increased the activity, and UTP and CTP were inferior as a phosphate donor.
 ...
PMID:Partial purification and properties of rat-heart adenosine kinase. 7 32

Adenosine kinase (EN 2.7.1.20) from rat and dog heart was purified until it was devoid of adenosine deaminase activity. A stimulation of adenosine kinase activity by dipyridamole was observed when the enzyme was assayed under optimal conditions. At low substrate concentrations adenosine kinase was inhibited by the drug. It increased the Km for adenosine sevenfold. The effects of dipyridamole were Mg2+-dependent. The adenosine-sparing action of dipyridamole at low substrate concentrations is in keeping with the vasodilatory action of the drug.
 ...
PMID:Dipyridamole affects myocardial adenosine kinase activity. 9 42

Activities of adenosine deaminase, adenosine kinase and purine nucleoside phosphorylase were determined in extracts prepared from human skin fibroblast strains derived from 7 normal newborn males and 4 normal adult males. All strains were harvested between passages 9 and 12. Adenosine deaminase activity in adult strains, 40.80 +/- 1.76 (mean +/- S.E.) nanomoles/min per mg protein, was almost twice the activity in neonatal strains, 22.40 +/- 3.02. This difference was significant at the 99.5% confidence level. Moreover, there was no overlap between the adult and neonatal activities. In contrast, adenosine kinase and purine nucleoside phosphorylase activities did not differ with the age of the donor.
 ...
PMID:Adenosine deaminase activity in human diploid skin fibroblasts varies with the age of the donor. 10 69

Activities of adenosine deaminase (ADA), adenosine kinase (AK), adenine phosphoribosyltransferase (APRT), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and purine nucleoside phosphorylase (PNP), all enzymes of the purine interconversion system, were determined in lymphocytes of 25 patients with chronic lymphatic leukemia (CLL) and in 23 controls. A statistically significant decrease of PNP activities and a reduction of ADA activities at borderline levels were found in the patients, whereas for the other enzymes assayed no deviation from normal values was observed.
 ...
PMID:Enzymes of the purine interconversion system in chronic lymphatic leukemia: decreased purine nucleoside phosphorylase and adenosine deaminase activity. 11 97

Adenosine is involved in the regulation of coronary blood flow, but its mechanism of action is not clear. The present investigation is an attempt to understand the mechanism(s) of uptake of adenosine in dispersed chick embryonic cardiac cells and its relationship to the adenosine hypothesis. Adenosine is readily taken up by these cardiac cells, and a small fraction is incorporated into adenine nucleotides, whereas a major fraction is deaminated to inosine. The mechanism of uptake is different in 12- to 15-day-old chick embryos compared to 16- to 22-day-old embryos. The younger embryo heart cells show the incorporation of adenosine into adenine mononucleotides of the incubation medium as well as all the adenine nucleotides of the cells, whereas the older embryo heart cells show incorporation of adenosine only into the adenine nucleotides of the cells. The isolated cells used in the present study do not leak any significant amounts of adenosine kinase and/or nucleotides, and free adenosine was not found in the cells, even with extracellular concentrations as high as 1 mM. The absence of free adenosine in isolated dispersed cells reflects the activities of adenosine kinase and adenosine deaminase and is compatible with the adenosine hypothesis for the regulation of coronary blood flow.
 ...
PMID:Uptake of adenosine by dispersed chich embryonic cardiac cells. 16 91

Purine metabolism and reutilization pathways were studied as they applied to normal and leukemic leukocytes. The enzyme activities were expressed in terms of the quantity of protein extracted and per 10(10) cells. Whereas the protein extracted and the enzyme activities from normal lymphocytes were relatively constant, considerable variation was noted in cases of chronic lymphocytic leukemia (CLL). This variability in the properties of the leukemic cells suggests that the difference may be useful in the subclassification of the leukemias. The studies of the complete enzyme system were done with 300 million cells. The extraction of 350,000 normal lymphocytes/mul gave a soluble protein concentration of 1.46+/-0.16 mg protein per ml, and the yield from the same number of CLL lymphocytes varied between 0.72 and 8.32 mg protein per ml. The 5'-nucleotidase activity gave an inverse correlation with the amount of extractable protein. In individual cases of CLL, the protein concentrations and the 5'-nucleotidase activities were found on either side of the normal values. In most cases, the adenosine deaminase of CLL lymphocytic cell extracts was lower than normal, and the adenosine kinase was higher; in the CLL cells, these two enzymes gave a positive correlation with one another. Little or no difference was observed in the activities of the purine nucleoside phosphorylases in extracts of normal or leukemic lymphocytes and granulocytes. The hypoxanthine-guanine and adenine phosphoribosyltransferase activities increased in the leukemic granulocytes but almost always showed a decrease in the CLL lymphocytes when compared with the normal cells. Most of the leukemic cells had greater than normal activities of the enzymes synthesizing phosphoribosyl pyrophosphate when tested with the purines. The total nucleotide produced from adenine and guanine with adenine- and hypoxanthine-guanine phosphoribosyltransferase was about equal in normal and leukemic lymphocytes, but the proportion of the adenosine 5'-triphosphate in the product was much greater with the leukemic cells. This suggested that the ribosyltransferase activities were the same in both types of cells, but the nucleoside kinases and the nucleoside diphosphate kinases were more active in the leukemic cells. Inosine monophosphate dehydrogenase was less active than normal in the CLL cell extracts and was not directly related to the amount of inosine monophosphate generated from hypoxanthine.
 ...
PMID:Purine metabolic cycle in normal and leukemic leukocytes. 18 45

A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a "permease" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.
 ...
PMID:Computer simulation of ischemic rat heart purine metabolism. I. Model construction. 19 89

Mutants deficient in adenosine kinase or adenine phosphoribosyltransferase activities were selected from the WI-L2 line of human lymphoblasts. The adenosine kinase-deficient mutant was still as sensitive as its parent to growth inhibition caused by adenosine deaminase was inhibited. Similarly, the adenine phosphoribosyltransferase mutant remained sensitive to growth inhibition caused by adenine. Thus, the toxicity of adenine and adenosine to human lymphoblasts is not mediated by nucleotides to which they may be converted.
 ...
PMID:Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes. 19

Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have shown that through the action of specific kinases, nucleosides can be "trapped" intracellularly in the form of 5'-phosphates. We therefore measured the ability of newborn human tissues to phosphorylate adenosine and deoxyadenosine, the substrate of adenosine deaminase, and also inosine, deoxyinosine, guanosine, and deoxyguanosine, the substrates of purine nucleoside phosphorylase. Substantial activities of adenosine kinase were found in all tissues studied, while guanosine and inosine kinases were detected in none. However, the ability to phosphorylate deoxyadenosine, deoxyinosine, and deoxyguanosine was largely confined to lymphocytes. Adenosine deaminase, but not purine nucleoside phosphorylase, showed a similar lymphoid predominance. Other experiments showed that deoxyadenosine, deoxyinosine, and deoxyguanosine were toxic to human lymphoid cells. The toxicity of deoxyadenosine was reversed by the addition of deoxycytidine, but not uridine, to the culture medium. Based upon these and other experiments, we propose that in adenosine deaminase and purine nucleoside phosphorylase deficiency, toxic deoxyribonucleosides produced by many tissues are selectively trapped in lymphocytes by phosphorylating enzyme(s).
 ...
PMID:Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s). 20 60


1 2 3 4 5 6 7 8 9 10 Next >>