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At least 19 recordsLinked to original sources
PubMed1979

Effect of diabetes and fasting on the uridine triphosphate content and uridine kinase activity of rat cardiac and skeletal muscle.

The influence of diabetes and starvation on uracil nucleotide metabolism in muscle was studied. It was found that the uridine triphosphate (UTP) content of heart and diaphragm muscle was decreased in fasted and streptozotocin-diabetic rats and that insulin treatment of diabetic animals restored the UTP concentration to normal levels. The ATP content of heart tissue was not altered under these conditions. It was also demonstrated that hemidiaphragms from streptozotocin-diabetic rats synthesized less UTP from uridine in vitro than hemidiaphragms from normal animals. Uridine kinase activity of extracts of cardiac and skeletal muscle from fasted and diabetic rats was lower than the activity found in extracts from control animals. It was concluded that uracil nucleotide synthesis by the salvage pathway is decreased in experimental diabetes and fasting.

Animals↗
PubMedDate not supplied

Prolonged contraction of isolated human and canine cerebral arteries induced by uridine 5'-triphosphate.

Uridine 5'-triphosphate (UTP) induced long-lasting contractions of isolated human brain arteries; contractions without decrement were observed for periods of up to 20-24 hours at which time the tissues were relaxed in a dose-dependent manner by theophylline. In some vessels, rhythmic oscillations accompanied the prolonged elevation in tension. In canine middle cerebral arteries, UTP produced dose related contractions within the dose range of 1.7 X 10(-6) to 1.7 X 10(-4) M; these responses were unaffected by methysergide 2.8 X 10(-7) M, phenoxybenzamine 2.9 X 10(-5) M or indomethacin 9.8 X 10(-6) M, suggesting that the UTP mechanism of action is probably independent of tryptaminergic or alpha adrenergic receptor activation, or of prostaglandin biosynthesis. The ability of UTP to produce prolonged contraction of cerebral vessels, thus, provides an in vitro preparation in which it is possible to study some of the basic mechanisms that are associated with cerebral vasospasm.

Animals↗
PubMed1977

Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping.

A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells.

Animals↗
PubMed1975

Reversible dissociation of a carbamoyl phosphate synthase-aspartate transcarbamoylase-dihydroorotase complex from ovarian eggs of Rana catesbeiana: effect of uridine triphosphate and other modifiers.

Glutamine-dependent carbanoyl phosphate synthase [ATP6carbamate phosphotransgerase (dephosphorylating), EC 2.7.2.9], aspartate transcarbamoylase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3), are copurified as a high-molicular-weight complex from extracts of unfertilized eggs of Rana catesbeiana. UTP is required to maintain the integrity of the complex during the last two purification steps. Removal of the nucleotide results in dissociation of the complex. Based on sedimentation behavior in glycerol gradients, the dissociated carbamoyl phosphate synthase has an apparent molecular weight of 260,000 +/- 20,000 and that of dihydroorotase is estimated at 280,000 +/- 20,000. Aspartate transcarbamoylase is broadly distributed over the gradient. The addition of ATP, 5-phosphoribosyl-1-pyrophosphate, Mg++, or inorganic phosphate to the dossociated complex results in the appearance of a peak of aspartate transcarbamoylase activity with an apparent molecular weight of 110,000 +/- 10,000. Icubation of a mixture of the dissociated enzymes with UTP and Mg++ leads to their reassociation into the high-molecular-weight complex.

Amidohydrolases↗
PubMedDate not supplied

[Metabolism of uridine triphosphate in rat liver].

Thiamin - a predecessor of transketolase coenzyme is shown to cause an increase in the intensity of labelled 14C orotic acid incorporation into UDP and UTP of the rat liver though the time of UTP exchange remains unchanged. Taking into account the data obtained, an assumption is advanced that the biosynthesis of pentoses in the pentosophosphate way of carbohydrates transformation in the rat liver proceeds in its non-oxidative branch with transketolase and transaldolase participating in the process.

Animals↗
PubMed1992

The L protein of vesicular stomatitis virus transcription complexes is specifically photolabelled by 5-azido-uridine 5'-triphosphate, an analogue of the RNA polymerase substrate uridine 5'-triphosphate.

A photoactive nucleotide analogue of UTP, 5-azido-uridine 5'-triphosphate (5-N3UTP), has been demonstrated to interact with the RNA polymerase of the vesicular stomatitis virus (VSV) transcription complex. Kinetic studies indicated that 5-N3UTP served as an efficient replacement for UTP in in vitro polymerase reactions. The Km for the azido analogue was 27 microM and that of the natural substrate, UTP, was 7 microM. Photolysis of [gamma-32P]5-N3UTP in the presence of VSV transcription complexes resulted in selective radio-labelling of the L protein. This photolabelling was saturable with an apparent Kd of 28 microM. The L protein was protected from [gamma-32P]5-N3UTP-mediated photolabelling by competing natural substrates (UTP, CTP, ATP, GTP). The stoichiometry of photoprobe incorporation into the transcription complex was close to unity with respect to the L protein. These data provide evidence that the nucleotide-binding domain of the VSV RNA polymerase contains amino acid residues of the L protein.

Affinity Labels↗
PubMed1977

The reduction of uridine 5'-diphosphate and uridine 5'-triphosphate in some transplantable rat hepatomas.

The reduction of uridine 5'-diphosphate (UDP) and uridine 5'-triphosphate (UTP) has been studied in normal adult rat liver, the Dunning hepatoma, and Morris 5123D and 7793 hepatomas. A new paper chromatographic method that separates and quantitates all the major products of the reduction and hydrolysis or other reactions of the substrate has been devised. All of the above tissues were able to reduce UDP and UTP at relatively slow rates ranging from 0.25 nmole of deoxycompound formed (deoxyuridine 5'-triphosphate) per mg protein per hr for liver to 3.5 nmoles deoxyuridine 5'-triphosphate for the Morris 7793 hepatoma when UTP was the substrate. In general, UTP was a better substrate than UDP. The method may also be used to measure cytidine 5'-diphosphate (CDP) reduction, and under the same conditions, the reduction of CDP proceeded at about 6 times the rate of UTP reduction in the Dunning hepatoma. Like CDP reduction, the reduction of UTP was strongly modulated by ATP. Reduction of UTP was insignificant with no ATP or 1.5 micronmoles ATP added to the reaction mixture and was maximal with 0.25 micronmole. The reduction of UTP was inhibited by deoxyuridine 5'-monophosphate, deoxythymidine 5'-triphosphate, deoxycytidine 5'-triphosphate, and deoxyribose 1'-phosphate. The effects of deoxyadenosine 5'-triphosphate varied, depending on its concentration in the reaction medium and whether UDP or UTP was a substrate. However, hydroxyurea did not inhibit reduction of UDP or UTP at concentrations that strongly inhibited CPD reduction. All of the tissues were able to hydrolyze [alpha-32P]deoxyuridine 5'-triphosphate readily to the diphosphate and monophosphate. It is suggested that the enzyme that reduces UTP or UDP may be different in these tissues from the enzyme that reduces CDP.

Animals↗
PubMed1975

Showdomycin, a nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase.

Showdomycin [2-(beta-D-ribofuranosyl)maleimide] is a nucleoside antibiotic containing a maleimide ring and which is structurally related to uridine. Showdomycin inhibited rat brain (Na+ + K+)-ATPase irreversibly by an apparently bimolecular reaction with a rate constant of about 11.01-mol- minus 1-min- minus 1. Micromolar concentrations of ATP protected against this inhibition but uridine triphosphate or uridine were much less effective. In the presence of K+, 100 MUM ATP was unable to protect against inhibition by showdomycin. These observations show that showdomycin inhibits (Na+ + K+)-ATPase by reacting with a specific chemical group or groups at the nucleotide-binding site on this enzyme. Inhibition by showdomycin appears to be more selective for this site than that due to tetrathionate or N-ethylmaleimide. Since tetrathionate is a specific reactant for sulfhydryl groups it appears likely that the reactive groups are sulfhydryl groups. The data thus show that showdomycin is a relatively selective nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase and inhibiton is likely due to the reaction of showdomycin with sulfhydryl group(s) at the nucleotide-binding site on this enzyme.

Adenosine Triphosphatases↗
PubMed1976

Isolation of a transcriptionally active chromosome from chloroplasts of Euglena gracilis.

A transcriptionally active chromosome has been isolated in highly purified form from choroplasts of Euglena gracilis, It contains chloroplast DNA, DNA-dependent RNA polymerase, and other proteins. Transcription occurs at low levels of endogenous DNA, and is indifferent to high levels of exogenous DNA. RNA chain elongation continues for several hours in vitro, and RNA chain initiation, determined by [gamma-32P]ATP incorporation, is continuous for at least 1 h in vitro. Maximal rates for RNA synthesis require only a divalent cation and the four ribonucleoside triphosphates. Apparent Km values for adenosine triphosphate, cytidine triphosphate, guanosine triphosphate, and uridine triphosphate are 4.0, 0.6, 2.5, and 2.3 muM, respectively. As would be expected for a DNA-dependent RNA polymerase, RNA synthesis is inhibited by actinomycin D. However, rifampicin and streptolydigin, inhibitors of procaryotic RNA synthesis, and alpha-amanitin, an inhibitor of eucaryotic nuclear RNA polymerases II and III, do not inhibt the RNA synthesis reaction. Heparin, which is a potent inhibitor of the initiation of RNA synthesis by a nontemplate bound RNA polymerase, also does not inhibit RNA synthesis. Isolation of transcriptionally active chromosomes should prove to be a useful method to study the mechanism of selective RNA transcription of eucaryotic chromosomes.

Aminoglycosides↗
PubMed1975

p-Aminobenzoate-p-aminobenzoate.

p-Aminobenzoate (PABA) synthase from Bacillus subtilis is an aggregate composed of two nonidentical subunits and has the following properties. (i) In crude extracts this enzyme catalyzes the formation of PABA in the presence of chorismate and either glutamine (amidotransferase) or ammonia (aminase). The amidotransferase activity is about 5- to 10-fold higher than the aminase activity and is stable for at least 1 week when frozen at -70 C. (II) Although no divalent cation requirement could be demonstrated with crude extracts, 2 mM ethylene-diaminetetraacetic acid completely inhibits both activities. (iii) After ammonium sulfate fractionation both the aminase and amidotransferase activities require Mg2+ and guanosine in addition to the substrates indicated above for optimal activity. The guanosine requirement can be replaced by guanosine 5'-monophosphate, guanosine 5'-diphosphate, and guanosine 5'-triphosphate but not by guanine, adenosine 5'-triphosphate, uridine 5'-triphosphate, cytidine 5'-triphosphate, thymidine 5'-triphosphate, inorganic phosphate, and phosphoribosylpyrophosphate. Furthermore, at a pH above 7.4 or below 6.4 activity is rapidly lost a 4 C, or -60 C. (IV) The enzyme is composed of two non-identical subunits, designated subunit A and subunit X. Subunit A has an estimated molecular weight of 31,000, whereas subunit X has an estimated molecular weight of 19,000. Subunit A has aminase activity but no amidotransferase activity; a mutation at the pabA locus results in the loss of PABA synthase activity. Subunit X, which is also a component of the anthranilate synthase complex, has no PABA synthase activity itself but complexes with subunit A to give an AX aggregate that can use glutamine as a substrate. (v) The molecular weight of the AX complex has been estimated at 50,000, suggesting a 1:1 ratio of subunits. (vi) The enzyme is readily associated and dissociated.

Aminobenzoates↗
PubMed1977

DNA synthesis inpermeable mouse ascites sarcoma cells.

DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-mercaptoethanol (pH 8.0). DNA-synthetic activity in the permeable cells was highly dependent on four deoxyribonucleoside triphosphates, adenosine triphosphates, Mg2+, and a proper ionic environment. The activity was stimulated about 50% by the addition of an appropriate concentration of cytidine triphosphate, guanosine triphosphate, and uridine triphosphate in an assay mixture containing adenosine triphosphate and four deoxyribonucleoside triphosphates. DNA synthesis was confined to the nucleus and was sensitive to N-ethylmaleimide and DNase. The activity assayed by the permeable cell system correlated closely with the DNA-replicating activity assayed by [3H]deoxythymidine incorporation in intact cells. The close correlation between DNA synthesis in vitro and in vivo was further confirmed in cultured sarcoma cells synchronized with DNA synthesis. Analysis of the DNA synthesized in vitro by alkaline cesium sulfate density gradient centrifugation showed that over half the DNA synthesized in permeable cells was due to elongation of strands initiated in vivo. The permeable cell system appears to be a useful method for examining DNA replication of cells in suspensions.

Animals↗
PubMed1977

Biological effects of inhibition of guanine nucleotide synthesis by mycophenolic acid in cultured neuroblastoma cells.

Mycophenolic acid, an inhibitor of inosinate dehydrogenase, had cytostatic and cytotoxic effects on cultured neuroblastoma cells. Proliferation was inhibited by 50% when cells were incubated with 0.07 micrometerM mycophenolic acid, and cell viability was reduced by 83% when cells were treated with 10 micrometerM mycophenolic acid for 24 hr. Treatment of monolayer cultures with mycophenolic acid reduced intracellular concentrations of guanosine triphosphate by 70% within 3 hr, whereas cytidine triphosphate and uridine triphosphate concentrations were significantly elevated, and adenosine triphosphate concentrations were increased only slightly. Reduction of cellular guanine nucleotides had differential effects on rates of macromolecular synthesis: incorporation of radioactive thymidine into acid-insoluble material was inhibited by mycophenolic acid to a much greater extent than was that of adenosine and leucine. Although proliferation of neuroblastoma cells was inhibited, differentiation, as judged by formation of neuronlike processes in serum-free medium, was unaffected by decreased intracellular concentrations of guanosine triphosphate.

Adenosine Triphosphate↗