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:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic 5'-nucleotidase, acting preferentially on IMP, GMP and their deoxyderivatives, can also behave as a phosphotransferase, operating a transfer of phosphate from a nucleoside monophosphate donor to a nucleoside acceptor which, besides a natural nucleoside, can be also an analog. The enzyme activity is stimulated by ADP, ATP and 2,3-bisphosphoglycerate (BPG). The concentration of effector required to attain half maximal activation (A0.5) for the bisphosphorylated compound is in the millimolar range, so that BPG seems to act as a physiological activator of 5'-nucleotidase only in erythrocytes. However, the combination of BPG and ADP brings about a significant increase of their respective affinity for the enzyme, lowering their A0.5 values approx. 4-times. The observation that BPG favors the phosphotransferase more than the hydrolase activity of 5'-nucleotidase stands for a key role of this metabolite in the regulation of the processes of activation of purine pro-drugs, in which this enzyme is involved.
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PMID:Synergistic action of ADP and 2,3-bisphosphoglycerate on the modulation of cytosolic 5'-nucleotidase. 864 38

AMP-deaminase (AMPDA) catalyzes the deamination of AMP to IMP and ammonia. Being an integral enzyme of the purine nucleotide cycle (PNC), AMPDA participates in catalytic deamination of amino acids and provides their involvement in a carbohydrate metabolism, fumarate being one of the end products of PNC. Since AMPDA competes with 5'-nucleotidase for AMP, it is responsible for regulation of a physiologically important active product of purine nucleotide metabolism, such as adenosine. Thus, this enzyme plays an important role in determining the physiological state of the organism in normal conditions as well as under the influence of some environmental factors and in some pathologies. The review sums up the information concerning the AMPDA participation in PNC operation in animal tissues, coding genes and enzyme activity regulation by various effectors, including, reversible phosphorylation and binding to myofibrils and myosin. Special attention is being given to a possible relationship of AMPDA activity deficiency to some neuromuscular pathologies.
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PMID:[Functional role and properties of AMP-deaminase]. 871 92

Cytosolic 5'-nucleotidase preferentially catalysing the hydrolysis of IMP, GMP and their deoxy derivatives, and endowed with phosphotransferase activity, was purified from calf thymus and its reaction mechanism was studied. In the presence of [32P]IMP, ATP and MgCl2, a covalent enzyme-phosphate intermediate was trapped by mixing with an SDS solution. Heart or acid treatment of the enzyme before incubation with radiolabelled substrate prevented formation of the intermediate. Furthermore, on the basis of studies on the kinetic parameters of the enzyme as function of pH, and of experiments on thiol oxidation and photo-oxidation, we suggest the involvement of cysteine and histidine residue(s) in the reaction mechanism.
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PMID:Mechanism of the reaction catalysed by cytosolic 5'-nucleotidase/phosphotransferase: formation of a phosphorylated intermediate. 876 Mar 65

A readily soluble 5'-nucleotidase was purified 1,800-fold from rat brain 105,000-g supernatant. The enzyme showed similarity to the 5'-nucleotidase ectoenzyme of plasma membranes. It exhibited a low Km for AMP, which was preferred over IMP as substrate. It was inhibited by free ATP and ADP and by alpha,beta-methylene ADP. The enzyme appeared to be a glycoprotein on the basis of its interaction with concanavalin A. It contained a phosphatidylinositol moiety because treatment with phosphatidylinositol-specific phospholipase C increased its hydrophilicity. A single subunit of Mr = 54,300 +/- 800 was observed, which is appreciably smaller than published values for the 5'-nucleotidase ectoenzyme or for other low- Km "soluble" 5'-nucleotidases. The soluble 5'-nucleotidase showed an elution profile on AMP-Sepharose affinity chromatography or on Mono Q ion-exchange chromatography different from that of the brain ectoenzyme. Forty-two percent of the soluble 5'-nucleotidase in brain 105,000-g supernatant did not bind to a Mono Q ion-exchange column because of its interaction with a soluble factor. This factor could be removed by chromatography on concanavalin A-Sepharose. The factor had the novel property of increasing the sensitivity of the purified soluble 5'-nucleotidase toward the inhibitor ATP by 20-fold. This factor was also able to increase the inhibition of brain 5'-nucleotidase ectoenzyme by ATP.
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PMID:A low-Km 5'-nucleotidase from rat brain cytosolic fraction: purification, kinetic properties, and description of regulation by a novel factor that increases sensitivity to inhibition by ATP and ADP. 876 9

AICA (5-amino-4-imidazolecarboxamide)-riboside is taken up by isolated rat hepatocytes and converted by adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) into AICAR (ZMP), an intermediate of the de novo synthesis of purine nucleotides. We investigated if, in these cells, a cycle analogous to the adenosine-AMP substrate cycle operates between AICAriboside and ZMP. When 50 microM ITu, an inhibitor of adenosine kinase, was added to hepatocytes that had metabolized AICAriboside for 30 min, the concentration of ZMP decreased immediately. This was mirrored by a reincrease of AICAriboside. Rates of the ITu-induced decrease of ZMP and the increase of AICAriboside, calculated at different concentrations of ZMP, were first order, up to the highest concentration of ZMP (approx. 5 mumol/g of cells). Dephosphorylation of ZMP added to crude cytosolic extracts of rat liver displayed hyperbolic kinetics, with a Vmax of 0.65 mumol/min per g protein and an apparent Km of 5 mM, and was markedly inhibited by Pi, an inhibitor of IMP-GMP 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5). We conclude that hepatocyte ZMP is continuously dephosphorylated, most likely by IMP-GMP 5'-nucleotidase, into AICAriboside, which is rephosphorylated into ZMP by adenosine kinase. Substrate cycling was also shown to occur between other nucleoside analogs and their phosphorylated counterparts.
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PMID:Substrate cycling between 5-amino-4-imidazolecarboxamide riboside and its monophosphate in isolated rat hepatocytes. 883 18

Intracellular AMP hydrolysis probably produces sufficient adenosine in ischemic heart to exert physiological activity. Because data on adenosine-producing systems in human heart are scarce, we measured 1) formation of adenosine (catabolites) in ischemic human heart slices and 2) cytoplasmic 5'-nucleotidase activity in human left ventricle. We also measured the latter in rat ventricle and cardiomyocytes. During the first 5 min of incubation, adenosine production in slices (n = 5) equaled 26 +/- 10 (SD) nmol.min-1.g wet wt-1, and total AMP content was 0.81 +/- 0.46 mM. Cytoplasmic IMP-preferring 5'-nucleotidase activity in homogenates of human heart (N-II, 167 +/- 78 mU/g, n = 23) was significantly higher than that of the AMP-preferring one (N-I, 107 +/- 61 mU/g, n = 24). Both isozymes were two to three times more active in rat heart than in human heart. Rat cardiomyocytes contained comparable amounts of the two 5'-nucleotidases. Kinetics of N-I isolated from explanted human heart displayed features similar to the enzyme from animal heart, with a Michaelis constant of 1.5 mM under maximally stimulated conditions. This form can provide the amount of adenosine found in ischemic slices. In conclusion, human heart shows lower cytosolic 5'-nucleotidase activities than rat heart. Nevertheless, cytosolic 5'-nucleotidase activity in human heart can easily account for adenosine formation during ischemia.
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PMID:Soluble forms of 5'-nucleotidase in rat and human heart. 896 93

The metabolism of purine nucleotides was studied in human peripheral blood lymphocytes from healthy subjects and patients with B-cell chronic lymphocytic leukemia. Nucleotide content was determined by HPLC. The rate of de novo synthesis of purine nucleotides was measured kinetically by following the incorporation of 14C-formate into the nucleotides of a lymphocyte suspension. The patterns of the main enzymes involved in purine nucleotide metabolism (those of the salvage pathway and catabolism) were estimated by a radiochemical method. Although the data expressed in relation to cells and protein showed some discrepancies, several common differences were evident in both cases. The main differences were an increase in NAD and IMP, a sharp decrease in 5'-nucleotidase activities and in total guanylate content and synthesis, and an increase in the A/G ratio in lymphocytes of patients with respect to controls. The changes in these parameters in CLL indicate an imbalance in purine metabolism and may play a specific role in the biology of the leukemia cell. They are also potential biochemical markers of lymphoid malignancies and may be useful in chemotherapic applications.
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PMID:Purine nucleotide metabolism: specific aspects in chronic lymphocytic leukemia lymphocytes. 919 62

Adenylosuccinase catalyses two reactions in purine metabolism: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) into aminoimidazole carboxamide ribotide (AICAR) along the de novo synthesis of purine nucleotides, and the conversion of adenylosuccinate (S-AMP) into AMP in the conversion of IMP into AMP. The hallmarks of adenylosuccinase deficiency are the presence of succinylaminoimidazole carboxamide riboside (SAICAriboside) and succinyladenosine (S-Ado) in body fluids. These normally undetectable succinylpurines are the products of the dephosphorylation, by cytosolic 5'-nucleotidase, of the two substrates of adenylosuccinase. The clinical picture of the enzyme deficiency is markedly heterogeneous with, as a rule, a profound, but nevertheless variable degree of psychomotor delay, often convulsions and/or autistic features, sometimes growth retardation and muscular dystrophy. The diagnostic tests that can be used for diagnosis, the enzyme and gene defects that have been identified, and the hypotheses that have been put forward to explain the pathophysiology of the disorder are reviewed.
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PMID:Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. 921 Nov 92

Human seminal plasma contains two enzyme activities both capable of dephosphorylating all nucleoside 5-monophosphates with different efficiency and specificity. Broad-spectrum soluble 5'-nucleotidase is the object of this paper which deals with the definition of the response of this enzyme to effectors, some physiological and others not naturally occurring. The enzyme did not show any product regulation as all the nucleosides tested caused a moderate effect on the hydrolysis of the substrates. Theophylline and other xanthine derivatives had no effect on enzyme activity, whereas glycerate 2,3-bisphosphate, like other soluble 5'-nucleotidases, caused a stimulation of the enzyme, especially toward CMP and UMP. 5-Deoxy-5-isobutylthiadenosine resulted in no inhibition of the hydrolysis of AMP and IMP. The enzyme was affected neither by monovanadate nor by decavanadate, whereas it was strongly inhibited by Ap5 A. Variations in adenylate energy charge did not cause any alteration of the enzyme activity toward AMP and only a slight decrease of the hydrolysis of IMP. These regulatory properties, distinct from those of other soluble 5'-nucleotidases, show that this form, newly isolated from human seminal plasma, is subject to an almost unique, tissue-specific regulation.
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PMID:Human seminal plasma soluble 5'-nucleotidase: regulatory aspects of the dephosphorylation of nucleoside 5'-monophosphates. 923 3

A unifying hypothesis is presented postulating an apocrine release of several seminal proteins which mix and reaggregate in seminal fluid, thereby eventually forming particles designated either as "prostasomes", "vesiculosomes" or "seminosomes". The term "aposomes" should be restricted to the blebs released from secretory cells in the rat dorsal prostate and coagulating gland. Three different proteins present in human seminosomes along with the respective antibodies have been used to identify the localization, function and hypothetical interaction with spermatozoa. The proteins were (1) seminal vesicle-derived fibronectin, (2) prostate-derived 5'-nucleotidase and (3) a hitherto unidentified 100 kD membrane protein from epididymis, seminal vesicle and prostate. I. Fibronectin is an extracellular matrix protein which is also secreted from the seminal vesicles participating in the formation of the seminal clot. Immunofluorescence and immunoelectron microscopy revealed a relatively broad distribution pattern of fibronectin immunoreactivity on spermatozoa from different donors. Adding a fibronectin antiserum at a moderate dilution to vital spermatozoa in vitro resulted in a significant increase in sperm motility. Purified plasma fibronectin added at various concentrations to a vital sperm preparation was found to inhibit sperm motility in a dose-dependent manner. Measurement of calcium fluxes in individual sperm in the presence of fibronectin showed a significant increase. These findings point to a possible post-testicular regulatory function of seminal fibronectin. 2.5'-Nucleotidase (5'-NT) is an enzyme that hydrolyzes nucleotides such as AMP or IMP into inorganic phosphate and the respective nucleoside. The highest amount and activity of 5'-nucleotidase was present in glandular cells of the prostate; much less was detected in seminal vesicles and epididymis. On spermatozoa, the enzyme was localized on the outer leaflet of the plasma membrane covering the acrosomal region. Addition of purified enzyme to an in vitro incubation system of spermatozoa had no effect on sperm motility. A slight reduction of overall motility, however, was observed after addition of 5'-NT antibody to the spermatozoa. When 5'-nucleotidase inhibitors and adenosine channel antagonists were added to the sperm incubation system, a clear-cut inhibition of sperm motility occurred in a dose-dependent manner. This result is interpreted as indicating a significant role of ecto-5'-nucleotidase in the regulation of sperm motility. 3. A polyvalent antiserum against native human prostasomes recognized antigens in the range of 10-14 kD and of approximately 100 kD, respectively, in seminal fluid and prostate homogenates. Immunohistochemical studies revealed the presence of respective antigens in the epididymis, seminal vesicles and the prostate. Immunoelectron microscopy of ultracryo-sections showed labeling both of the apical plasma membrane in the prostate, as well as intraluminal secretory particles indicating the apocrine i.e. plasma-membrane bounded release of these particles. The secretory elements are termed "seminosomes". An affinity-purified fraction within the antiserum recognizes a 100 kD protein which is present both in the apical plasma membrane of the male genital glands, but also in the sperm head and principal piece of human spermatozoa. Incubation of spermatozoa with seminosomes and the respective purified antiserum had no effect on sperm motility. This is in contradistinction to former reports on motility increase induced by the so-called prostasomes.
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PMID:The role of apocrine released proteins in the post-testicular regulation of human sperm function. 936 95


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