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:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mixed adrenergic agonist epinephrine, at a 10 microM concentration, stimulated cyclic AMP production and glycerol release in the epididymal adipose tissue of ob/ob male mice. These effects when tested, respectively, after 7 min in the presence and after 60 min in the absence of theophylline were, however, 7- and 5-fold lower than in lean controls. The alpha-adrenergic blocker phentolamine and adenosine deaminase (which destroys extracellular adenosine) did not restore a normal lipolytic response to epinephrine in the adipose tissue of ob/ob mice. These data provide indirect evidence against a hyperactive mechanism in the coupling of alpha-adrenergic receptors and adenosine receptors to Ni, the guanine nucleotide-binding inhibitory component of adenylate cyclase, as the cause of reduced lipolysis in the adipose tissue of ob/ob mice.
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PMID:Indirect evidence against a contribution of the guanine nucleotide-binding inhibitory component of adenylate cyclase to impaired lipolysis in the epididymal adipose tissue of congenitally obese (ob/ob) mice. 299 42

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 micrograms/ml) caused a two-to threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N6-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase. Pretreatment of adipocytes with pertussis toxin (5 micrograms/ml) for 180 min resulted in a five- to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment. The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.
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PMID:Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms. 299 84

Using the flask-incubated fat cell system, alterations in glycerol release (lipolysis) and cAMP accumulation were determined after incubation with isoproterenol or forskolin. These agents caused concentration-dependent increases in both cAMP accumulation and lipolysis. The maximum responses to forskolin for each variable were greater than the corresponding responses to isoproterenol. The maximum responses to isoproterenol for both cAMP accumulation and glycerol release were increased by the presence of either adenosine deaminase or theophylline. Under these conditions, high concentrations of isoproterenol continued to increase cAMP accumulation while having no further effect on lipolysis. These results support the concept that the maximum response to isoproterenol alone was limited by the accumulation of cAMP within the cells. The maximum response to isoproterenol in the presence of either theophylline or adenosine deaminase (and to forskolin) was limited by some step in the lipolytic process distal to cAMP accumulation. The relationships between cAMP levels and lipolysis for isoproterenol and forskolin were found to be different. A 6-fold increase in cAMP levels was sufficient to maximally increase lipolysis with isoproterenol, whereas the maximum lipolytic response to forskolin was associated with a 20-fold increase in cAMP levels. A plot of log cAMP vs. glycerol release resulted in linear relationships for both drugs. The slope of the line for isoproterenol was significantly greater than that for forskolin. At any given concentration of cAMP the corresponding lipolytic response was greater for isoproterenol than for forskolin.
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PMID:Relationships between cyclic AMP levels and lipolysis in fat cells after isoproterenol and forskolin stimulation. 301 46

alpha 2 and beta-adrenergic binding and action were studied in subcutaneous adipocytes from the gluteal region in females and males. The beta-selective antagonist [3H]dihydroalprenolol and the alpha 2-selective antagonist [3H]yohimbine were used to identify the beta- and the alpha 2-receptor, respectively. The biological effects mediated by these receptors were determined by measuring the glycerol release induced by isoproterenol (beta-receptor agonist) and by clonidine (alpha 2-receptor agonist). The study consisted of health volunteers (eighteen females and fifteen males). Compared to men the alpha 2-receptor binding was increased by 73% (P less than 0.01) in adipocytes from females. From Scatchard analysis it was determined that the increased binding was due to an increased receptor number (438 v. 262 fmol mg-1 protein, P less than 0.001) with unaltered Kd (1.18 v. 1.35 nmol l-1, P greater than 0.05). This increased alpha 2-receptor binding in female and adipocytes was associated with a significantly increased sensitivity (P less than 0.05) and maximal antilipolytic effect of clonidine (P less than 0.05). The beta-receptor binding was similar in adipocytes from females and males. However, isoproterenol was significantly more lipolytic in female adipocytes (P less than 0.01). Since the combination of theophylline and adenosine deaminase also was significantly more lipolytic in female adipocytes the enhanced effect of isoproterenol then seemed to be due to mechanisms not directly related to the hormone-beta-receptor binding. Finally, the mixed beta- and alpha 2-receptor agonist, adrenaline showed biphasic effects on lipolysis, with stimulatory effect at low concentrations (less than 500 nmol l-1) and pronounced inhibitory effect at higher concentrations (greater than 1 mumol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased alpha 2- but similar beta-adrenergic receptor activities in subcutaneous gluteal adipocytes from females compared with males. 301 1

Adipocytes incubated with adenosine deaminase (ADA) showed: (1) increased amounts of fatty acids in the medium; (2) increased glucose incorporation into acylglycerol glycerol; (3) decreased glucose incorporation into acylglycerol fatty acids; (4) a co-ordinate decrease in the sensitivity of lipolysis and glucose incorporation into acylglycerol to insulin; (5) similar effects on glucose incorporations in perifused and normal incubations. The decrease in fatty acid synthesis by perfusion was found to be dependent on the presence of insulin or fatty acids, and independent of the effects of ADA. The significance of the effects of perifusion, ADA and insulin are discussed in relation to effects of fatty acids.
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PMID:The response of adipocyte glucose metabolism and fatty acid release to adenosine deaminase, insulin and perifusion. Investigation of intermediary metabolism by perifusion. 304 1

Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) from Bacillus cereus NCIB 8122 has been purified to electrophoretic homogeneity by ammonium sulfate precipitation, gel filtration through Sephadex G-100, DEAE-Sephadex A-50 chromatography and ion-exchange HPLC on DEAE-Polyol. The enzyme activity is stabilized (at temperatures from 0 degrees C to 40 degrees C) by 50 mM NH4+ or K+, while it is irreversibly lost in the absence of these or a few other monovalent cations. Glycerol (24% by volume) helps the cation in stabilizing the enzyme activity above 40 degrees C, but also exerts per se a noticeable protecting effect at room temperature. B. cereus adenosine deaminase displays the following properties: Mr on Sephadex G-200, 68,000; Mr in SDS-polyacrylamide gel electrophoresis, 53,700; optimal pH-stability (in the presence of 50 mM KCl) over the range 8-11 at 4 degrees C, and maximal catalytic activity at 30 degrees C between pH 7 and 10; Km for adenosine around 50 microM over the same pH range and Km for 2'-deoxyadenosine around 400 microM.
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PMID:Purification, stability and kinetic properties of highly purified adenosine deaminase from Bacillus cereus NCIB 8122. 309 80

The influence of prolonged energy restriction (1250 kJ for 4 weeks) on insulin's antilipolytic action was investigated in abdominal adipocytes of obese subjects. An attempt was made to discriminate between dietary influences per se and indirect influences caused by changes in the concentration or action of adenosine. Prolonged energy restriction resulted in about a 3.5-fold increase in basal lipolytic rate which was associated with a corresponding increase in maximal response to insulin. Both these effects could be mimicked by adenosine deaminase (1.6 micrograms/ml) which increased glycerol release of adipocytes from fed donors to levels normally seen during starvation suggesting that the improvement of lipolytic responsiveness to insulin during energy restriction was an apparent one only, due to the fact that glycerol release was increased. To identify dietary influences that selectively affect insulin action the effects of insulin were compared with those of other antilipolytic agents in the presence of adenosine deaminase. Maximally effective concentrations of prostaglandin E2, clonidine and N6-phenylisopropyladenosine almost completely suppressed glycerol release before and during starvation. The extent of inhibition produced by these latter compounds was therefore related to basal activity by the same linear relationship in all experimental settings. By contrast insulin only partially depressed glycerol release and the relationships between basal activity and response to maximal concentrations of insulin were significantly different before and during starvation (P less than or equal to 0.01) in the presence of adenosine deaminase indicating that starvation selectively influences insulin action via mechanisms that are unrelated to the effects of other antilipolytic compounds. It is concluded that the main effect of energy restriction on insulin's antilipolytic action is an apparent one which is secondary increased lipolytic activity. Direct dietary effects on insulin action became apparent upon removal of endogenous adenosine. These tend to limit the maximal response to insulin and may be due to changes at the post-binding level but could also reflect an intrinsic property of insulin's antilipolytic action.
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PMID:Antilipolytic action of insulin in abdominal adipocytes of obese subjects before and during energy restriction. Influence of adenosine deaminase. 330 11

Weight-maintaining fat-rich, "prudent," carbohydrate-rich, as well as energy-restricted diets (300 kcal/d) were fed in succession for 7 d to 12 healthy males of ideal body weight under metabolic ward conditions. At the end of each period isolated fat cells were prepared from subcutaneous abdominal adipose tissue and incubated in vitro in the absence or presence of adenosine deaminase, either alone or in combination with various lipolytic or antilipolytic hormones and agents. Variations in total energy intake and dietary composition had characteristic and specific effects on fat cell lipolysis in vitro. High carbohydrate and prudent diets resulted in low rates of nonstimulated glycerol release and impaired insulin action in the presence of adenosine deaminase (320 mU/ml). High-fat and energy restricted diets were characterized by high rates of nonstimulated glycerol release. Sensitivity of antilipolysis to insulin and prostaglandin E2 was 10 to 200 times lower respectively on energy-restricted than on fat-rich diets. The effects of alpha 2- and beta-adrenergic catecholamines and of N6-phenylisopropyladenosine were not affected by the preceding diets.
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PMID:Influences of variation in total energy intake and dietary composition on regulation of fat cell lipolysis in ideal-weight subjects. 330 2

The mechanisms responsible for the large increases of intracellular ATP levels seen after isolated rabbit proximal tubules are treated with exogenous adenine nucleotides were studied. Exogenous ATP was rapidly degraded via adenosine as far as hypoxanthine. Degradation of AMP to adenosine was substantially inhibited by beta-glycerol phosphate. In studies of the ability of individual exogenous purines to increase intracellular ATP levels, single large doses of adenosine were less effective than equimolar doses of exogenous ATP but were substantially more effective than exogenous inosine or hypoxanthine. Exogenous guanine derived compounds increased only cell GTP. Incremental delivery of smaller doses of adenosine to maintain medium levels greater than 5 microM or inhibition of adenosine deaminase with erythro-9-[3-(2-hydroxynonyl)]adenine or 2'-deoxycoformicin enhanced the nucleoside's effectiveness. However, the initial increase of cell ATP was still greater after treatment with exogenous ATP than after adenosine and, in the presence of adenosine deaminase inhibition, larger increases of cell ATP were produced by 50 microM adenosine than by 250 microM adenosine. These observations are most consistent with substrate inhibition of adenosine kinase by adenosine. Furthermore, the adenosine kinase inhibitor, 5-iodotubercidin, prevented the increases of cell ATP resulting from exogenous adenosine or exogenous ATP. These studies demonstrate how the differential uptake and utilization characteristics of nucleosides and bases can fully account for the increases of intracellular nucleotides produced in isolated tubules by exogenous purines.
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PMID:Modulation of cell nucleotide levels of isolated kidney tubules. 334 10

The effects of adenosine and of some products of its metabolic degradation on lipolysis were studied in rat fat cells isolated from epididymal adipose tissue. Basal glycerol release was not affected by adenosine and by uric acid, but it was significantly increased by inosine (1-100 microM) and by hypoxanthine (10-100 microM). Adenosine was more effective than inosine in antagonizing the lipolytic response of fat cells to theophylline. Also hypoxanthine and uric acid exerted a very potent, noncompetitive antagonism towards theophylline. Norepinephrine-induced lipolysis was inhibited by adenosine, hypoxanthine and uric acid approximately to the same extent, while inosine was ineffective at this level. Adenosine deaminase (0.5 U/ml) increased basal as well as theophylline- and norepinephrine-induced lipolysis. Moreover, adenosine deaminase enhanced the lipolytic rate in cells incubated with low (0.1, 1 microM) and, to a lesser extent, with high (10, 100 microM) inosine concentrations. These results suggest that inosine is the adenosine metabolite that may accumulate in the incubation medium following fat cell treatment with adenosine deaminase, thus contributing to the stimulatory effects of this enzyme on lipolysis.
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PMID:A reexamination of the effects induced by adenosine and its degradation products on rat fat cell lipolysis. 340 Dec 55


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