Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A modified Gilman assay was used to determine the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) in rapidly filtered cells and in the culture filtrates of Pseudomonas aeruginosa, Escherichia coli K-12, and Bacteroides fragilis. In P. aeruginosa cultures, levels of cAMP in the filtrate increased with the culture absorbance (3.5 to 19.8 X 10(-9) M) but did not vary significantly with the carbon source used to support growth. Intracellular concentrations (0.8 to 3.2 X 10(-5) M) were substantially higher and did not vary appreciably during growth or with carbon source. Sodium cAMP (5 mM) failed to reverse the catabolite repression of inducible glucose-6-phosphate dehydrogenase (EC 1.1.1.49) synthesis caused by the addition of 10 mM succinate. Exogenous cAMP also had no discernible effect on the catabolite repression control of inducible mannitol dehydrogenase (EC 1.1.1.67). P. aeruginosa was found to contain both soluble cAMP phosphodiesterase (EC 3.1.4.17) and membrane-associated adenylate cyclase (EC 4.6.1.1) activity, and these were compared to the activities detected in crude extracts of E. coli. B. fragilis crude cell extracts contain neither of these enzyme activities, and little or no cAMP was detected in cells or culture filtrates of this anaerobic bacterium.
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PMID:Cyclic adenosine 3',5'-monophosphate levels and activities of adenylate cyclase and cyclic adenosine 3',5'-monophosphate phosphodiesterase in Pseudomonas and Bacteroides. 18 75

Neuroblastoma adenylate cyclase is activated by 2-chloroadenosine, prostaglandin E1, and 5'-guanylylimidodiphosphate [GMP-P(NH)P]. However, the process of activation by the first two compounds is different from that induced by the third. Prostaglandin E1 and 2-chloroadenosine activation is rapid, producing elevated activities which are constant throughout a 20-min assay. In contrast, GMP-P(NH)P activation is slow and although the activity is elevated within 1 min, it continues to increase for up to 12 min before attaining a maximal constant value. Activation is more rapid when either prostaglandin E1 or 2-chloroadenosine is present with GMP-P(NH)P. Activation of the enzyme by GMP-P(NH)P appears to be retarded by endogenous nucleotides as suggested by the following observations: (a) if the enzyme is incubated at 30 degrees with 5 mM MgCl2 for 5 to 7 min, GMP-P(NH)P then produces maximal activation without a detect able lag; (b) if, during this incubation, nucleotides, a nucleotide regenerating system, or EDTA (instead of MgCl2) are present, subsequent GMP-P(NH)P activation is slow; and (c) in the assays which contain a nucleotide regenerating systm and MgATP as substrate, the Km for GMP-P(NH)P is 6 +/- 2 muM. However, in the assays using MgAMP-P(NH)P as substrate but no nucleotide regenerating system, the Km is 0.5 +/- 0.2 muM. GPD and GTP do not replace GMP-P(NH)P as an enzyme activator in any of our assays systems, and in fact, are potent inhibitors of GMP-P(NH)P enzyme activation. Prostaglandin E1 and 2-chloradensine do not alter significantly the Km for GMP-P(NH)P but do decrease the ensyme's sensitivity of GDP. Proposed is a hysteretic model of neuroblastoma adenylate cyclase, which shows the enzyme responding slowly to rapid changes in GMP-P(NH)P concentration due to the slow displacement of the tightly bound endogenous guanine nucleotides by GMP-P(NH)P. Additionally, prostaglandin E1 and 2-chloroadenosine increase the rate of GMP-P(NH)P activation by decreasing the enzyme's affinity for these endogenous guanine nucleotides.
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PMID:Neuroblastoma adenylate cyclase. Role of 2-chloroadenosine, prostaglandin E1, and guanine nucleotides in regulation of activity. 93 91

Male mice of 7 different strains were injected i.p. with 400 mg/kg of butylated hydroxytoluene (BHT). 2 and 4 days later, the incorporation of thymidine into pulmonary DNA was significantly increased in all treated animals and this was accompanied by an increase in lung weight and pulmonary DNA. Thymidine kinase activity and DNA polymerase activity were enhanced in the lungs of BHT-treated animals and maximum activity of these enzymes appeared to precede maximum thymidine incorporation by 24 h. 3 days after BHT a good correlation was found between administered dose and thymidine kinase activity. Measuring the activity of this enzyme might serve as a convenient biochemical marker to follow and to quantitate BHT-produced cell proliferation in lung. The concentrations of cyclic AMP and the activity of adenylate cyclase were not altered by BHT on days 1-9 after administration. BHT produced also some dose-dependent, time-dependent increases in the activities of pulmonary 5'-nucleotidase and glucose-6-phosphate dehydrogenase (G6PDH), but had little effect on isocitric dehydrogenase (ICDH), pyruvate kinase (PK) and lactic dehydrogenase (LDH).
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PMID:Biochemical paramters of BHT-induced cell growth in mouse lung. 124 55

The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.
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PMID:Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters. 171 81

In continuation of earlier studies on murine neoplastic liver lesions, we characterized by histochemical methods the phenotype of hepatocellular adenomas and carcinomas induced by single injections of diethylnitrosamine (1.25, 2.5, or 5.0 micrograms/g of body weight) in 15-day-old C57BL/6 x male C3H F1 mice. The hepatocellular adenomas were composed predominantly of basophilic cells but stored excessive amounts of fat and glycogen in large portions of the tumors. Irrespective of the carcinogenic dose, the adenomas showed a consistent histochemical pattern. Glycogen synthase and phosphorylase were highly active in the hepatocytes that stored glycogen. In cells poor in, or free of, this polysaccharide, these enzymes were only moderately active or even inactive. In glycogen-storing parts of the adenomas, the activity of adenylate cyclase was reduced compared with normal liver parenchyma, but in fat-storing portions it was elevated. In a few adenomas, uniform increase in adenylate cyclase activity could be encountered. The levels of ATPase, acid phosphatase, and glucose-6-phosphatase were either increased or decreased. Glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase showed an increased activity in all adenomas compared with preneoplastic foci, which in turn exhibited a higher glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activity than the surrounding parenchyma or the liver of untreated controls. The hepatocellular carcinomas showed remarkable histochemical changes compared with adenomas. The levels of fat and glycogen and the activities of glycogen synthase, phosphorylase, and in most cases also that of glucose-6-phosphate dehydrogenase, were reduced significantly. In contrast, adenylate cyclase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase, and also alkaline phosphatase showed a striking elevation in developing carcinomas. Similar, although more pronounced, histochemical changes were seen in the advanced hepatocellular carcinomas. These observations indicated that progression from adenomas to hepatocellular carcinomas was associated with a change in the activity of several enzymes involved in cell membrane function, glycogen metabolism, the oxidative pentose phosphate pathway, and glycolysis.
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PMID:Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine. 184 80

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
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PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Chronic administration of the estrogen 17 beta-estradiol induces kidney tumors in male Syrian hamsters within 6 months of initial exposure. Although these tumors have previously been studied histologically and histochemically and have been postulated to be derived from proximal tubular and/or interstitial cells, there exists no unambiguous evidence for an epithelial or mesenchymal origin. To elucidate the histogenesis of these neoplasms, kidney sections of hamsters treated with estradiol for 4, 5, and 6 months and age-matched untreated controls were investigated histologically and histochemically. Proliferating foci were observed in kidneys exposed to estradiol for 5 and 6 months. They consisted of clusters of spindle-shaped cells forming solid blocks, cords, or branches located between tubules. These foci were judged to be precursors of larger tumors identified in the latter treatment group. The histological and histochemical profile of foci and tumors matched closely. These lesions were marked by very high activities of alkaline phosphatase, adenyl cyclase, and glucose 6-phosphate dehydrogenase. In contrast, glycogen content and activities of glucose 6-phosphatase, succinate dehydrogenase, and gamma-glutamyl transpeptidase were low or absent. Immunofluorescence of the intermediate filaments revealed that foci and tumors solely expressed vimentin and desmin but not cytokeratin. The morphology, enzyme histochemical pattern, and immunofluorescence strongly support a mesenchymal origin of the estradiol-induced hamster kidney tumors studied. The neoplasms were probably derived from vascular smooth muscle cells of a cell subtype particularly sensitive to hormonal stimulation and transformation.
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PMID:Histochemical analysis of the development of estradiol-induced kidney tumors in male Syrian hamsters. 244 29

In the fully grown Bufo arenarum oocyte, carbohydrate breakdown during the autumn-winter season is accomplished mainly through the glycolytic pathway followed by the Krebs cycle. During the breeding season (spring-summer), carbohydrates are used mainly through the pentose phosphate cycle and through the variant of the Krebs cycle known as the glutamic aspartic cycle. The metabolism operating in the oocytes was determined using the following parameters: 1) the capacity of isolated mitochondria to oxidize citrate and fumarate; 2) the enzymatic activities of phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G-6-PDH); and 3) citrate and ATP compartmentalization. The present paper shows that follicle-stimulating hormone (FSH) would be one of the factors responsible for summer metabolism, since ovary fractions obtained from winter specimens treated with the hormone acquired the metabolic characteristics corresponding to oocytes obtained from breeding-season animals. From dose-response, and response in the function of time curves, it could be assumed that the optimum doses and times were 0.1 micrograms FSH/ml of incubation medium and 30 min treatment, respectively. The metabolic effect of FSH upon oocytes could be mediated by the adenylate cyclase-cAMP system, since treatment of ovaric fractions with cAMP 10(-3) M reproduced the effects obtained with the hormone. In addition, 0.02 mg/ml tetracycline proved to block the effect of FSH. A direct metabolic action of FSH on body cavity oocytes (without follicle cells) was observed when submitting these oocytes to the same hormonal treatment.
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PMID:Effect of follicle-stimulating hormone on metabolism and maturation in Bufo arenarum oocytes. 250 14

In a stop-experiment using the hepatocarcinogen N-nitrosomorpholine, as well as glycogenotic and related lesions, hepatocellular foci with a different histochemical pattern were identified. The outstanding features of these hepatic foci, which may progress to hepatocellular adenoma, were increased activities of mitochondrial glycerol-3-phosphate dehydrogenase (mG3PD), glycogen synthase, pyruvate kinase and glucose-6-phosphatase detected by enzyme histochemistry. Since no decrease in activity of any of the enzymes examined were seen in these foci, compared with normal liver, the term enzymatically hyperactive focus (EHF) is proposed for this type of lesion. Only at the stage of overtly nodular growth did these lesions exhibit some of the characteristic changes seen in nodules developing from glycogenotic foci, namely elevated activities of glucose-6-phosphate dehydrogenase, gamma-glutamyl transferase and glutathione-S-transferase P as well as decreased activities of adenosine-triphosphatase, glucose-6-phosphatase and adenylate cyclase. Some of these enzymes have been used widely in morphometric studies as markers for preneoplastic and neoplastic lesions. The inability to detect early EHF may lead to an underestimation of preneoplastic liver lesions in quantitative studies. Although there are apparent differences in the histochemical patterns of glycogen storing foci and early EHF, these differences tend to disappear during progression to overtly neoplastic lesions. In studies comparing the phenotypic alterations in different types of preneoplastic hepatic lesions, the recognition of EHF may contribute to the distinction of obligatory from facultative phenomena during transformation.
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PMID:Unusual histochemical pattern in preneoplastic hepatic foci characterized by hyperactivity of several enzymes. 256 54

Nucleoside diphosphokinase (NDK) of human platelets has been purified by chromatography on Blue Sepharose CL-6B gel (purification factor of 950) and shown to be free of adenylate kinase, ATPase and adenylate cyclase. The molecular weight was 70,000 with subunits of 17,000. The pH optimum was 8.0 Km values for ATP and dTDP were determined in two ways using the pyruvate kinase-lactate dehydrogenase coupled enzyme assay. Values of 0.38 and 0.20 mM were obtained for ATP and 0.29 and 0.21 mM for dTDP. Km values for ADP (0.024 mM) and GTP (0.12 mM) were determined with the hexokinase-glucose-6-phosphate dehydrogenase coupled enzyme assay. These values are in agreement with those reported for NDK from other sources. Theophylline, which inhibits the NDK activity of intact platelets and platelet membrane preparations and inhibits the ADP-induced shape change of platelets, was shown to be a competitive inhibitor of both the free and phosphorylated forms of NDK with competitive inhibition constants (Kic) of 9.3 and 9.6 mM respectively. Papaverine, another cAMP phosphodiesterase inhibitor, which also inhibits the ADP-induced shape change of platelets, had no inhibitory effect on platelet NDK. It was concluded that the inhibitory effect of theophylline on the activity of the purified enzyme was due to the structural similarity between the methylxanthine and the adenine moiety of ADP.
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PMID:Isolation and kinetic studies of nucleoside diphosphokinase from human platelets and effects of cAMP phosphodiesterase inhibitors. 302 50


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