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:3.5.1.4 (deaminase)
5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of degradative enzymes and enzyme inhibitors were examined on the inhibitory actions of adenosine, AMP and ATP on atrial muscle and on the cholinergic responses of the ileum to transmural stimulation of the guinea-pig, in order to determine whether ATP responses are mediated by its breakdown products, AMP and adenosine. In both the atria and the ileum, adenosine deaminase reduced responses to ATP, although when combined with 5'-nucleotidase it had no further effect. In the atrium, the 5'-nucleotidase inhibitor, alpha,beta-methylene ADP (APCP), had no effect on its own, but prevented the potentiating effect of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) on responses to ATP. In the ileum, EHNA had no effect, but APCP potentiated responses to ATP. The enzyme 5'-AMP deaminase was shown to have a non-specific inhibitory effect on purine responses in both preparations. It is concluded for both preparations, that (1) the inhibitory responses to ATP are partly mediated by AMP and adenosine following the ectoenzymatic breakdown of ATP, and partly mediated by ATP itself, and (2) that AMP as well as adenosine can act directly on P1-purinoceptors. It is suggested that of the two breakdown products of ATP, AMP and adenosine, a larger proportion of the response is mediated by AMP in the ileum, whereas adenosine is the major mediator in the atrium.
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PMID:Stimulation of P1-purinoceptors by ATP depends partly on its conversion to AMP and adenosine and partly on direct action. 632 Dec 10

The concentration of insulin that produces half-maximal stimulation of glycolysis in stripped soleus muscle preparations is decreased from approximately 100-10 muunits/ml by the presence of adenosine deaminase in the incubation medium. This suggests that adenosine decreases insulin sensitivity. The effect of the deaminase is abolished by addition of the adenosine analogue, N6-phenylisopropyladenosine which is not metabolised by the deaminase. The effect of the deaminase in isolated soleus muscle is similar to that of a period of physical training of the rat.
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PMID:Effect of adenosine deaminase and an adenosine analogue on insulin sensitivity in soleus muscle of the rat. 634 99

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

To test the hypothesis that adenosine mediates striated muscle blood flow, the cremaster muscle microcirculation was exposed to a continuous superfusion (10-30 min) of either a control, adenosine deaminase (7 micrograms protein/ml), or theophylline (10(-5) M) solution before, during, and following twitch contraction. Small arteriolar diameter and (dual-slit) blood flow velocity were continuously measured for 3 min before and after 2 min of electrical stimulation at 10, 5, or 2 Hz. Estimated arteriolar volume flow was calculated at 10-s intervals. The peak and average arteriolar diameter, peak and average estimated volume flow, duration of the exercise evoked response, and the total estimated volume of blood delivered in the 3-min postexercise period were reduced by deaminase as a function of stimulus frequency relative to a paired control. Deaminase reduced total estimated blood flow by 44, 35, and 22% at 10, 5, and 2 Hz, respectively. Although theophylline was more damaging to the tissue at a dose that was equieffective with deaminase, it produced a consistent reduction in peak and average arteriolar diameter and estimated volume flow after 5-Hz exercise. If changes in small arteriolar diameter are proportional to tissue blood flow changes, then these observations support the hypothesis that adenosine contributes to contraction-induced hyperemia in skeletal muscle in free-flow conditions and that its regulatory contribution depends on the intensity of the metabolic stimulus. Alternatively, these data could implicate adenosine in exercise-induced capillary recruitment.
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PMID:Reduction of contraction-induced arteriolar vasodilation by adenosine deaminase or theophylline. 646 28

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

Serial-flow cytometric analysis of DNA content of T lymphoblasts (MOLT-4) and B lymphoblasts (MGL-8) was performed to correlate the cytotoxic properties of adenosine deaminase inhibition with alterations of DNA synthesis and disruptions of the cell cycle. The addition of deoxyadenosine up to 50 mumol/L potently decreased the growth of T lymphoblasts, and these changes were enhanced with the addition of 100 mumol/L homocysteine thiolactone. These conditions caused a virtual absence of cells from S and G2M phases after 24 hours. The DNA distribution was similar in cells cultured for 24 hours in 50 mumol/L deoxyguanosine or 2.5 mumol/L hydroxyurea. These observations suggested accumulation of cells in the G1 phase. T lymphoblasts cultured with up to 50 mumol/L adenosine had a substantial decrease in growth, which was not modified by the addition of homocysteine thiolactone. Cell cycle distributions of T lymphoblasts cultured for 24 to 48 hours under these conditions showed mild decreases in the G2M population. The addition of adenosine up to 50 mumol/L decreased the growth of B lymphoblasts, and these changes were enhanced by the addition of 100 mumol/L homocysteine thiolactone. These conditions induced mild decreases in the S-phase population in B lymphoblasts. The addition of deoxyadenosine, even with homocysteine thiolactone, did not modify growth in B lymphoblasts and the cell-cycle distributions were indistinguishable from distributions of control populations after 24 and 48 hours. The observations provide independent support for a reduction of DNA synthesis associated with cytotoxicity during adenosine-deaminase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered cell cycle distributions of cultured human lymphoblasts during cytotoxicity related to adenosine deaminase inhibition. 660 57

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
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PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22

An inherited deficiency of adenosine deaminase (Ado deaminase; adenosine aminohydrolase, EC 3.5.4.4) causes severe combined immunodeficiency disease in humans. A similar deficiency in purine nucleoside phosphorylase (Puo phosphorylase; purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) engenders a selective cellular immune deficit. To elucidate the possible metabolic basis for the contrasting immunologic phenotypes, we compared the toxicity toward mature resting human lymphocytes of the Ado deaminase substrates deoxyadenosine and adenosine and the Puo phosphorylase substrate deoxyguanosine. When Ado deaminase was inhibited, micromolar concentrations of deoxyadenosine progressively killed nondividing helper and suppressor-cytotoxic T cells, but not B cells. The toxicity required phosphorylation, with subsequent dATP formation. The deoxyadenosine analogs 2-chlorodeoxyadenosine, 2-fluorodeoxyadenosine, and adenine arabinonucleoside also killed resting T cells. Cell death was unrelated to inhibition of adenosylhomocysteinase (EC 3.3.1.1) but was preceded by a gradual decline in ATP levels. As much as 1 mM deoxyguanosine did not impair resting lymphocyte viability, despite the synthesis of dGTP. The combination of 200 microM adenosine plus 500 microM homocysteine thiolactone killed dividing lymphocytes but had no discernible toxic effect toward resting T cells, which accumulated adenosylhomocysteine over a 4-hr period but thereafter excreted the nucleoside into the culture medium. The different clinical syndromes associated with genetic deficiencies of Ado deaminase and Puo phosphorylase may be explained by the ability of dATP to kill mature resting T lymphocytes by depleting ATP levels.
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PMID:Possible metabolic basis for the different immunodeficient states associated with genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase. 680 16

Adenosine deaminase from Bacillus cereus is quite unstable, similarly to other bacterial deaminases, but it shows a peculiar stabilizing effect by some monovalent cations. These include K+, Li+, NH4+ and to a lesser extent Cs+. Maximal stabilization of the deaminase is exerted by K+ at concentrations higher than 20 mM. The enzyme can be rapidly inactivated by sulphydryl reagents such as p-hydroxymercuribenzoate. Since adenosine deaminase from B. cereus, in addition to monovalent cations, is stabilized also by dithiothreitol, a possible influence of monovalent cations on the reactivity of some sulphydryl groups on the enzyme has been suggested.
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PMID:Preliminary characterization of adenosine deaminase from Bacillus cereus. 681 69

Hereditary deficiency of the enzyme adenosie deaminase (adenosine aminohydrolase, EC 3.5.4.4) results in an immunodeficiency syndrome characterized by a marked reduction in circulating lymphocytes. We have administered 2'-deoxycoformycin, a potent inhibitor of adenosine deaminase, to a patient with a lymphoproliferative malignancy. The clinical consequences of pharmacologic inhibition of adenosine deaminase activity included an abrupt decrease in the lymphocyte count, abnormalities of renal and hepatic function, and hemolytic anemia. The plasma concentrations of adenosine and deoxyadenosine rose to peak values of 13 microM and 5 microM, respectively, and erythrocyte dATP levels increased to 110 pmol/10(6) cells over 9 days. There was a corresponding decrease in erythrocyte ATP levels from 128 to < 6 pmol/10(6) cells. A similar profound reductin in ATP occurred in the erythrocytes of a second patient. The rapid and unexpected depletion of ATP associated with dATP accumulation may account, at least in part, for the toxicity associated with 2'-deoxycoformycin administration. The inverse relationship of ATP and dATP raises major questions about the control of energy metabolism in erythrocytes.
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PMID:ATP depletion as a consequence of adenosine deaminase inhibition in man. 696 3


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