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

The existence of nonadrenergic, noncholinergic nerve components in the autonomic nervous system is now well established. They are strongly represented in the gastrointestinal tract of all vertebrates and have been identified in a variety of other organs, including lung, trachea, bladder, esophagus, eye, seminal vesicles, and possibly parts of the vascular and central nervous systems. Their ultrastructural identification and transmission properties are known and their physiological role is beginning to be understood, at least in the gastrointestinal tract. Evidence that ATP is the transmitter released from nonadrenergic, noncholinergic (purinergic) nerves includes: (a) synthesis and storage of ATP in nerves; (b) release of ATP from the nerves when they are stimulated; (c) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (d) the presence of Mg-activated ATPase, 5'nucleotidase, and adenosine deaminase, enzymes, which inactivate ATP; (e) drugs (including 2-substituted imidazolines, 2,2'-pyridylisatogen and dipyridamole), that produce similar blocking or potentiating effects on the response to exogenously applied atp and nerve stimulation.
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PMID:Purine nucleotides. 1 17

Experiments over the past decade have revealed a third component in the autonomic nervous system which is neither adrenergic nor cholinergic. These nerves are strongly represented in the gastrointestinal tract of a wide range of vertebrate species and have also been identified in lung, trachea, retractor penis, bladder, oesophagus, eye, seminal vesicle and in some parts of the cardiovascular system and brain. Evidence has been presented that the principal active substance released by these nerves in the gut is a purine nucleotide, probably ATP, and they have therefore been termed 'purinergic'. The evidence includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) mimicry by exogenously applied ATP of the action of nerve-released transmitter; (4) the presence of Mg2+-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) the similar blocking and potentiating effects produced by drugs on the responses to exogenously applied ATP and nerve stimulation. A tentative model for the synthesis, storage, release and inactivation of ATP during purinergic nerve transmission is proposed. Some properties of purinergic receptors are described.
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PMID:The purinergic nerve hypothesis. 2 31

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.
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PMID:The breakdown of adenine nucleotides in glucose-depleted human red cells. 4 52

1. The adenosine deaminase has an approximate molecular weight of 130,000-140,000 and the composition of two polypeptide units (mol. wt about 68,000) is suggested, by means of SDS disc electrophoresis. 2. Both the alpha (Vm/Km) and beta (Vm) parameters were varied with pH and temperature. RSS (relative substrate specificity) adenosine and deoxyadenosine values for alpha and beta were 1.2 and 1.1, respectively. 3. Adenine, 2'-, 3', 5'-AMP, 5'-deoxyAMP, ADP and ATP were not deaminated by the enzyme. 4. Inhibition by Mg2+ was found in reaction with adenosine at pH 8 but not with deoxyadenosine at the same pH. Mn2+, which did not affect the reaction rate at pH 4 and 5, showed competitive inhibitory effects at pH 6, 7 and 8.
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PMID:Purification and properties of the adenosine deaminase from the midgut gland of a marine bivalved mollusc, Atrina spp. 4 29

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.
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PMID:Partial purification and properties of rat-heart adenosine kinase. 7 32

Conversion of adenosine to inosine is decreased in adenosine deaminase (ADA)-deficient fibroblasts at all concentrations of adenosine tested. Adenosine is not differentially toxic to ADA-deficient fibroblasts except at very high (5 X 10(-4) -1 X 10(-3) M) adenosine levels. Conversion of [14C] adenosine to GTP is not decreased in ADA-deficient cells compared with control cell strains. Adenosine conversion to ATP is the same as that in mutant cells except at high nonphysiologic concentrations, at which it is slightly decreased in ADA-deficient fibroblasts. This effect is probably not related to the biochemical pathology of ADA-deficient lymphocytes in vivo. Uridine, a pyrimidine compound, "rescues" control cells from the effects of adenosine toxicity, as previously reported, but it has no protective effect on ADA-deficient fibroblasts. This suggests that uridine will have no therapeutic role in the treatment of the ADA-deficient form of severe combined immunodeficiency (SCID) disease.
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PMID:Purine dysfunction in cells from patients with adenosine deaminase deficiency. 13 30

Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in "receptive relaxation" of the stomach, "descending inhibition" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of "large opaque vesicles," which can be distinguished from the "large granular vesicles" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The "rebound contraction" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type.
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PMID:Comparative studies of purinergic nerves. 17 88

The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established.
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PMID:Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate. 18 3

Effects of adenosine and some of its derivatives on beef protein kinase activity were investigated in vitro. Adenosine rapidly inhibited protein kinase activity in a dose-dependent manner. Significant inhibition occurred with 10 muM and half-maximal inhibition at 100 muM adenosine. Inhibition was almost complete with 5 mM adenosine. Inhibition was similar whether protein kinase activity was assayed with or without cyclic AMP. The inhibition by adenosine was reversed by increasing the concentration of ATP and Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP. Addition of adenosine deaminase to the incubation medium prevented the inhibition induced by adenosine. Intact 1 and N6 positions of adenosine were important for the inhibition since their modification was associated with loss of inhibition. Modification of the 8 position of adenosine decreased, but did not abolish, the inhibition. The 2 and 3 position of ribose did not seem to be critical since 2- and 3-deoxyadenosine produced inhibition similar to that of adenosine.
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PMID:Effects of adenosine and its derivatives on protein kinase activity of beef thyroid. 18 58

A cyclic AMP-adenosine binding protein from mouse liver has been purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis in the absence and presence of sodium dodecyl sulfate and by analytical ultracentrifugation. The binding protein had a Stokes radium of 48 A based on gel chromatography. Both the purified binding protein and the binding activity in fresh cytosol sedimented as 9 S on sucrose gradient centrifugation. The homogeneous protein had a sedimentation coefficient (S20, w) of 8.8 x 10-13 s, as calculated from sedimentation velocity experiments. By use of the Stokes radius and S20, w', the molecular weight was calculated to be 180,000. The protein was composed of polypeptides having the same molecular weight of 45,000 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thus appeared to consist of four subunits of equal size. The isoelectric point, pI = 5.7. The binding capacity for cyclic AMP increased by preincubating the receptor protein in the presence of Mg2+ ATP. This process, tentatively termed activation, was studied in some detail and was shown not be be be accompanied by dissociation, aggregation, or phosphorylation of the binding protein. Cyclic AMP was bound to the protein with an apparent dissociation constant (Kd) of 1.5 x 10-7 M. The binding of cyclic AMP was competitively inhibited by adenosine, AMP, ADP, and ATP whose inhibition constants were 8 x 10-7 M, 1.2X 10-6 M, 1.5 X 10-6 M, and higher than 5 x 10-6 M respectively. A hyperbolic Scatchard plot was obtained for the binding of adenosine to the activated binding protein, indicating more than one site for adenosine. The binding of adenosine to the site with the highest affinity (Kd=2 x 10-7 M) for this nucleoside was not suppressed by excess cyclic AMP and was thus different from the aforementioned cyclic AMP binding site. Cyclic GMP, GMP, guanosine, cyclic IMP, IMP, and inosine did not inhibit the binding of either cyclic AMP or adenosine. The binding protein had no cyclic AMP phosphodiesterase, adenosine deaminase, phosphofructokinase, or protein kinase activities, nor does it inhibit the catalytic subunit of the cyclic AMP-dependent protein kinase.
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PMID:An adenosine 3':5'-monophosphate-adenosine binding protein from mouse liver. 18 23


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