Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Loss of ATP accompanying accumulation of dATP has recently been reported to occur in the erythrocytes and lymphoblasts of patients with T lymphocytic leukemia during treatment with deoxycoformycin, an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) that causes the accumulation of deoxyadenosine. We have studied the mechanisms responsible for adenine ribonucleotide depletion in cultured human CEM T lymphoblastoid cells treated with deoxycoformycin and deoxyadenosine. Accumulation of dATP was accompanied by depletion of total soluble adenine ribonucleotides without change in the adenylate energy charge, by the route ATP --> AMP --> IMP --> inosine --> hypoxanthine; conversion of IMP to AMP and de novo purine synthesis were inhibited in these cells. ATP degradation did not occur in a mutant of CEM that was incapable of phosphorylating deoxyadenosine, or in a B cell line with very limited ability to accumulate dATP. We found that dATP and ATP were both able to stimulate markedly the deamination of AMP by lymphoblast AMP deaminase; dAMP was a poor substrate for this enzyme (K(m) = 2.4 mM, vs. 0.4 mM for AMP). Similarly, dATP as well as ATP caused marked activation of IMP dephosphorylation by a lymphoblast cytoplasmic nucleotidase. Inhibition of intracellular AMP deaminase with coformycin prevented degradation of adenine ribonucleotides without affecting dATP accumulation. We propose that ATP-dependent phosphorylation of deoxyadenosine generates ADP and AMP. Simultaneously, dATP accumulation stimulates deamination of AMP, but not dAMP, and the dephosphorylation of IMP to inosine. Coupling of AMP degradation to ATP utilization in deoxyadenosine phosphorylation maintains the adenylate energy charge despite net depletion of cellular ATP.
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PMID:Mechanism of deoxyadenosine-induced catabolism of adenine ribonucleotides in adenosine deaminase-inhibited human T lymphoblastoid cells. 628 40

AMP deaminase, 5'-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5'-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.
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PMID:AMP deaminase, 5'-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia. 628 39

Expression of the enzyme terminal deoxynucleotidyl transferase (TdT) was studied in human thymus during ontogeny and development. In five fetal thymus samples, the enzyme activity was barely detectable. At birth, the terminal transferase activity remained low. Maximum expression of the enzyme activity occurred between 10 and 40 mo of age. Analysis of six other enzyme activities, adenosine kinase, deoxyadenosine kinase, AMP deaminase, dAMP deaminase, 5' nucleotidase, and adenosine deaminase confirmed the normal status of the thymic tissue. A careful analysis of thymic architecture revealed that involution did not occur as a result of the disease process that necessitated cardiac surgery. By immunofluorescence, the TdT antigen was localized exclusively in the nucleus of cortical thymocytes. Protein immunoblotting studies indicated that human thymic terminal transferase exists as a single high m.w. species in individuals under 30 mo of age. Thereafter, a variant m.w. species is detectable. The increase in expression of this enzyme coincides with the increase observed in serum immunoglobulin levels during maturation and precedes the maximum development of the human thymus.
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PMID:Expression of terminal deoxynucleotidyl transferase in human thymus during ontogeny and development. 640 69

The mechanisms for cell toxicity with adenosine deaminase inhibition by 2'-deoxycoformycin (dCF) in non replicating lymphoid cells include S-adenosylhomocysteine (SAH) hydrolase inactivation and reduction of cellular ATP content. These postulates were explored in a patient with T-CLL receiving dCF with a resultant fall in peripheral blood lymphocytes from 740 X 10(9)/1 to 90 X 10(9)/1 over 15 d. In red cells there was complete inhibition of adenosine deaminase and SAH hydrolase activities, progressive deoxyadenosine triphosphate (dATP) accumulation and ATP depletion but no significant alteration in adenosine monophosphate (AMP) deaminase activity or distribution in purine intermediates from radioactive adenosine. In T-CLL lymphocytes, there was incomplete lymphoid SAH hydrolase inactivation, reduced AMP deaminase activity and progressive dATP accumulation. The limited decrease in lymphocyte ATP content was related more to dCF administration than dATP accumulation, nor accompanied by significant changes in the distribution of purine intermediates from adenosine. These findings suggest that ATP depletion with dCF therapy does not reflect AMP deaminase activity modulation nor is of critical importance for cell toxicity. The exact role for elevated cellular dATP content and SAH hydrolase inactivation in this toxicity remains to be established.
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PMID:The biochemical and clinical consequences of 2'-deoxycoformycin in T cell chronic lymphocytic leukaemia. 660 10

AMP deaminase and adenosine deaminase activities were assayed in the subcellular fractions of pig thyroid gland. AMP deaminase is localized in the cytosolic fraction; however, this enzyme showed remarkable tendency to bind with the subcellular particulate fractions. Adenosine deaminase is also localized in the cytosolic fraction but in contradistinction to AMP deaminase, adenosine deaminase under the same experimental conditions has no tendency of binding to subcellular particulate fractions. The significance of AMP deaminase binding to subcellular particulate fractions is discussed.
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PMID:Intracellular distribution of AMP deaminase in the pig thyroid gland. 673 76

Chromatography on phosphocellulose column revealed changes in the elution profile of 14 day-old chicken embryo and adult hen skeletal muscle AMP deaminase. In the presence of 5 mM potassium the enzyme from embryo muscle exhibited a sigmoid-shaped plot of the reaction rate versus substrate concentration. The increase of KCl concentration up to 100 mM diminished distinctly sigmoidicity of the plot. Micromolar concentrations of ADP or ATP activated, whereas GTP at the same concentrations inhibited the embryo and hen skeletal muscle AMP deaminase while 5 mM KCl was present in the incubation medium. 100 mM potassium concentration diminished the effect of ADP and ATP but not of GTP. Palmitoyl-CoA inhibited strongly the embryo skeletal muscle adenylate deaminase but had no effect on the activity of the hen enzyme. Alanine inhibited only the adult hen enzyme. The embryo and hen AMP deaminase differed also in the specificity to adenylate analogues and exhibited a different dAMP/AMP ratio. The data presented indicate that kinetic and regulatory properties of the two developmental forms of AMP deaminase are different.
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PMID:Regulatory properties of 14-day embryo and adult hen skeletal muscle AMP deaminase. 688 96

Adenylate deaminase (AMP deaminase; AMP aminohydrolase, EC 3.5.4.6), a tetrameric enzyme found at particularly high concentrations in skeletal muscle, has previously been shown to bind strongly to the subfragment-2-portion of myosin in vitro and to the ends of the A band in vivo. It is shown here that when adenylate deaminase is dialyzed with skeletal myosin during formation of synthetic filaments at pH 7.0 it decorates the filament at 14.3-nm intervals, presumably in the region of exposed backbone between crossbridge levels. Optical diffraction of the aggregates reveals both enhancement of reflections arising from underlying myosin organization and other reflections arising from adenylate deaminase arrangement on the filament surface. Adenylate deaminase can thus be used as a specific label in the study of myosin presence and organization.
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PMID:Adenylate deaminase binding to synthetic thick filaments of myosin. 693 63

AMP deaminase (adenylate deaminase; AMP aminohydrolase, EC 3.5.4.6), a large flat tetrameric enzyme found in skeletal muscle, binds strongly and specifically to the subfragment-2 region of rabbit skeletal muscle myosin. This allows its use as a structural probe in myosin and myosin rod aggregation studies. When mixed with a preparation of isolated native thick filaments, AMP deaminase decorates the entire filament backbone except for the central bare zone. Binding is particularly ordered in the banded region, where 11 stripes of about 43-nm spacing on either side of the bare zone have been observed in studies of isolated A-bands. No systematic absence of deaminase is seen here, indicating that the presence of the C-protein and H-protein bands does not make the binding site inaccessible to the tetramer. Optical diffraction patterns of the decorated filaments show the expected 42.9-nm periodicities and a reflection indexing at 28.6 nm. Because of the bulkiness of the tetramer relative to the number of available binding sites at each 14.3-nm interval along the filament shaft, the helix net is being sampled at a lower frequency than is the underlying myosin organization. As a result, reflections on layer lines other than orders of 42.9 nm are also observed (e.g., 57.2); these reflections strongly indicate a structure based on a 12/1 primitive helix. The results appear to eliminate the symmetric double two-fold and three-fold models of thick filament structure but are consistent with an asymmetric four-fold structure.
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PMID:Structural studies of isolated native thick filaments from rabbit psoas muscle with AMP deaminase decoration. 695 10

1. The breakdown of the adenine nucleotide pool provoked by the replacement of the O(2)/CO(2) gas phase by N(2)/CO(2) was studied in isolated rat hepatocytes with the purpose of defining the pathway of the catabolism of AMP in anoxic conditions. 2. Approx. 40% of the adenine nucleotide pool was lost after 40-60 min of anoxia. In hepatocytes from fed rats there was a slow disappearance of ATP. This is explained by the presence of glycogen stores, allowing the generation of ATP by anaerobic glycolysis. In hepatocytes from 24h-starved rats, ATP almost completely disappeared within 5 min, and was partly replaced by an accumulation of AMP. This indicates that another mechanism protects the adenine nucleotide pool in the starved state. In both conditions, the loss of adenine nucleotides was mainly accounted for by an accumulation of uric acid, owing to the oxygen-dependence of urate oxidase. 3. Incubation of the hepatocytes before the suppression of O(2) with coformycin at concentrations known to inhibit selectively adenosine deaminase did not result in an accumulation of adenosine and did not influence the formation of uric acid. This indicates that the degradation of AMP does not proceed by way of 5'-nucleotidase under these conditions. In the presence of coformycin at concentrations which are inhibitory to AMP deaminase, however, the formation of uric acid was nearly suppressed, demonstrating that the initial degradation of AMP was catalysed by the latter enzyme. 4. The accumulation of AMP in the starved state can be explained by the pronounced decrease in ATP, the major stimulator of AMP deaminase, and the enhanced increase in P(i), one of its physiological inhibitors. The modifications of these effectors can also explain the increased inhibition of the cytoplasmic 5'-nucleotidase, shown by the accumulation of IMP in the absence of coformycin, in hepatocytes from starved rats. 5. Reoxygenation of the hepatocytes after 20 min of anoxia induced a prompt regeneration of ATP, which reached concentrations equal to the pre-existing concentration of AMP. 6. No explanation was found for the accumulation of IMP observed after preincubation of the hepatocytes with 0.1mum-coformycin, since the activities of the IMP-metabolizing enzymes were not influenced by this inosine analogue.
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PMID:The pathway of adenine nucleotide catabolism and its control in isolated rat hepatocytes subjected to anoxia. 708 1

1. Activity of glutamate dehydrogenase and adenylate deaminase were measured in the livers of carnivores (animals characterised by intake of a high dietary protein). 2. Animals studied (ferret, cat, dog, hedgehog, rat, hamster, mouse, cow, pig and rabbit) were kept on their natural diet. 3. Glutamate dehydrogenase activity showed no variation between carnivores and non-carnivores. 4. Adenylate deaminase activity was significantly higher in carnivores than in non-carnivores. 5. In carnivores, adenylate deaminase might be the rate limiting enzyme in the terminal deamination of L-amino acids. 6. Elevation of adenylate deaminase might be due to the acidogenic effect of the diet.
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PMID:Activity of adenylate deaminase and glutamate dehydrogenase in the liver: species and dietary variation. 708 16


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