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At least 19 recordsLinked to original sources
PubMed1978

Stabilization and solubilization of bovine corpus-luteum adenylate cyclase. The effects of guanosine triphosphate, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and Tris/hydrochloric acid concentration on enzyme activity.

1. Adenylate cyclase of the washed 600g sediment of bovine corpus-luteum homogenate is stimulated by p[NH]ppG (guanosine 5'-[beta,gamma-imido]triphosphate), the imido analogue of GTP, and to a lesser extent by GTP itself. Activation by p[NH]ppG is not reversed by extensive washing before assay, but can, however, be reversed by NaF. 2. Both p[NH]ppG and NaF stabilize the enzyme during incubation at 37 degrees C. NaF also causes an irreversible activation, but only of part of the potentially NaF-activatable adenylate cyclase; there are possibly two components of the adenylate cyclase system, which can be distinguished by their response to NaF. 3. Solubilization of the adenylate cyclase activity in the 600g sediment, by using the non-ionic detergent Lubrol-PX, gave variable yields. A relationship between the magnitude of NaF stimulation of the 600g-sediment enzyme and the yield of soluble activity derived from the sediment was recognized. The results suggest that the pre-existing state of the enzyme complex in vivo is reflected by the response in vitro to NaF and may determine the success with which activity can be solubilized. 4. The absolute yields of soluble activity could be increased by p[NH]ppG preactivation of the 600g sediment. During the development of the maximally active state by preincubation with p[NH]ppG the enzyme passes through a stage in which Lubrol solubilization is increased, but the maximally active state is itself less amenable to solubilization. p[NH]ppG activation causes the appearance of NaF-inhibited states, which appear to be preferentially solubilized by Lubrol-PX.

Adenylyl Cyclases↗
PubMed1973

Kinetics of phosphate incorporation into adenosine triphosphate and guanosine triphosphate in bacteria.

Escherichia coli cells were labeled with (33)PO(4) for several generations and then (32)PO(4) was added, samples were taken at various times, and adenosine triphosphate (ATP) and guanosine triphosphate (GTP) were purified from an acid extract. The ratio of (32)P/(33)P in each of the six phosphate species was determined and compared to the ratio expected at isotopic steady state. The rate constants of the simplest network of pools which could explain the data, and were consistent with metabolic pathways, were then calculated. In the range of times studied (30 to 3,000 s at 21.5 C) the following generalizations can be made. (i) The gamma-phosphate at ATP requires 2,200 s to achieve 50% of its final specific activity and behaves as if it were exchanging with another species 4.4 times as large, with this other species turning over in 540 s. (ii) The beta-phosphate of ATP and the gamma-phosphate of GTP are in equilibrium with the gamma-phosphate of ATP. (iii) The specific activity of the gamma-phosphate of GTP lags 66 s behind the gamma-phosphate of ATP. (iv) The alpha-phosphates of ATP and GTP have equal specific activities which lag far behind the other four phosphates. A single precursor pool with a turnover time of 416s fits the data best, although a fair fit can be obtained assuming several sequential precursor pools with much shorter turnover times. These findings are consistent with known biosynthetic pathways and the probable flows through them, including the relationship of nucleotide biosynthesis to ribonucleic acid synthesis and turnover.

Adenosine Triphosphate↗
PubMed2004

Kinetic properties of voltage-gated Na+ currents in rat muscular sympathetic neurons with and without adenosine triphosphate and guanosine triphosphate in intracellular solution.

Voltage-gated Na+ currents were recorded from anatomically identified postganglionic muscular sympathetic neurons without and with ATP and GTP in the intracellular solution. The main findings of the study were that cells without ATP and GTP in the intracellular solution express a higher amplitude and greater density of voltage-gated Na+ current, and their Na+ current activates faster and also inactivates faster time dependently. The current is also steady-state inactivated to a lesser degree and recovers from inactivation more slowly in cells without added ATP and GTP. These findings suggest that the presence of ATP and GTP, substrates for channel phosphorylation, changes the kinetic properties of Na+ currents.

Adenosine Triphosphate↗
PubMed1982

beta, gamma-Peroxy analogs of adenosine and guanosine triphosphate: synthesis and biological activity.

Extended analogs of adenosine triphosphate (ATP) and guanosine triphosphate (GTP), in which a peroxide bridge replaces the terminal bridge-oxygen of the triphosphate chain, have been synthesized. The ability of beta, gamma-peroxy-ATP to inhibit or substitute for ATP in representative enzyme systems and that of beta, gamma-peroxy-GTP, for FTP in protein synthesis was tested.

Adenosine Triphosphate↗
PubMed1995

Guanosine triphosphate cyclohydrolase I regulates nitric oxide synthesis in renal proximal tubules.

The synthesis of nitric oxide by proximal tubule-inducible nitric oxide synthase requires tetrahydrobiopterin as a cofactor. To determine whether tetrahydrobiopterin synthesis is required for nitric oxide production, nitrite release by mouse proximal tubule cells treated with 2,4-diamino-6-hydroxypyrimidine, an inhibitor of the rate-limiting enzyme in the de novo synthesis of tetrahydrobiopterin from guanosine triphosphate, guanosine triphosphate cyclohydrolase I, was measured. Treatment with lipopolysaccharide (0.1 micrograms/mL) and interferon-gamma (100 U/mL) for 12 h increased nitrite production from 2.7 +/- 0.2 to 25.4 +/- 1.3 nmol/mg of protein (P < 0.001; N = 9). 2,4-Diamino-6-hydroxypyrimidine (6 mM) reduced lipopolysaccharide/interferon-gamma-induced nitrite production by 53.1 +/- 3.4%. Sepiapterin, a substrate for tetrahydrobiopterin synthesis via the dihydrofolate reductase-dependent pterin salvage pathway, prevented the inhibition by 2,4-diamino-6-hydroxypyrimidine, an effect that was blocked by methotrexate. In conclusion, guanosine triphosphate cyclohydrolase I activity is required for cytokine-induced nitric oxide production by proximal tubular epithelium. The inhibition of guanosine triphosphate cyclohydrolase I could prove useful in the treatment of nitric oxide-mediated renal disorders.

Animals↗
PubMed2001

A novel method for the measurement of dissolved adenosine and guanosine triphosphate in aquatic habitats: applications to marine microbial ecology.

A novel method for the measurement of dissolved adenosine-5'-triphosphate and guanosine-5'-triphosphate (D-ATP and D-GTP, respectively) in marine and freshwater habitats was developed and applied to samples collected from the oligotrophic North Pacific Ocean. Both D-ATP and D-GTP are co-precipitated by authigenically formed Mg(OH)(2) and can be concentrated by factors greater than 200-fold, for subsequent measurement by the firefly luciferin-luciferase bioluminescence reaction. The detection limit for this method was 2-3 pmol ml(-1) of concentrated sample (equivalent to an in situ concentration of 10 pM) with a 5% precision at concentrations of 10 pmol ml(-1) or above.A significant positive correlation (P<0.001) was observed between particulate ATP (P-ATP) and D-ATP in water samples collected from Station ALOHA (22.75 degrees N, 158 degrees W; depth profiles 0-1000 m). The highest concentrations of dissolved nucleotides were found in the euphotic zone (0-175 m) below which the concentrations were low and relatively invariant. The dissolved nucleotide pools generally exceeded their corresponding particulate pools.Using radioisotopic tracer techniques and the new concentration method, turnover times for both particulate and dissolved nucleotides can be determined. The ability to measure concentrations and follow nucleotide tracers accurately in a very dilute environment provides a unique opportunity to address questions on microbial community metabolism, nutrient dynamics and energy flux.

Adenosine Triphosphate↗
PubMed1990

Human neutrophils contain a protein kinase C-like enzyme that utilizes guanosine triphosphate as a phosphate donor. Cofactor requirements, kinetics, and endogenous acceptor proteins.

Investigations of protein kinase C (PKC) activity have focussed on protein phosphorylation using adenosine triphosphate (ATP), not guanosine triphosphate (GTP), as the phosphate donor. In a continuing study of the enzymology of the PKC of human neutrophils, we wanted to determine if there might be protein kinases that do use GTP as a phosphate donor. Soluble extracts or detergent-extracted fractions of human neutrophils were used as enzyme sources. Phosphorylation of histone using [gamma-32P]-GTP was 31% as effective as [gamma-32P]-ATP. Phosphorylation with GTP depended on Ca2+, Mg2+, and phospholipid, just as the ATP, and the Ca2+ requirements were similar. In all cases, H-7, an inhibitor of ATP-supported PKC activity, blocked GTP-utilizing activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that similar endogenous proteins were phosphorylated with ATP or GTP. The apparent Km and Vmax for the enzyme(s) for both phosphate donors were identical, although these were modified by treatment with Triton X-100. GTP competitively inhibited use of ATP by PKC; however, low concentrations of ATP enhanced GTP-utilizing kinase activity in some cases. Non-hydrolyzable forms of ATP and other nucleotide triphosphates were inhibitory. Detergent treatment also markedly altered the number of proteins phosphorylated by either nucleotide. The major protein phosphorylated in the soluble or detergent extract was a single polypeptide band in the 34 Kd range. These studies are the first to explicitly examine the possible phosphorylation by neutrophil PKC using GTP and point to a potential alternative mode of enzyme activity. Since high concentrations of GTP are available within neutrophils, the ability of PKC or a PKC-like enzyme to use this nucleotide may have important ramifications in signal transduction.

Adenosine Triphosphate↗
PubMed1995

Interactions of tubulin with guanine nucleotides that have paclitaxel-like effects on tubulin assembly: 2',3'-dideoxyguanosine 5'-[alpha,beta-methylene]triphosphate, guanosine 5'-[alpha,beta-methylene]triphosphate, and 2',3'-dideoxyguanosine 5'-triphosphate.

Despite reduced affinity for the exchangeable nucleotide binding site of tubulin relative to GTP, 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) and guanosine 5'-[alpha, beta-methylene]triphosphate [pp(CH2)pG] are highly active in promoting tubulin assembly. Like the antimitotic drug paclitaxel, which interacts with the same part of the beta-tubulin molecule as exchangeable-site GTP, both analogs enhance nucleation reactions and promote formation hyperstable polymers. These observations led us to synthesize the doubly modified analog 2',3'-dideoxyguanosine 5'-[alpha, beta-methylene]triphosphate [pp(CH2)pddG]. We compared the effects of pp(CH2)pddG to those of ddGTP, pp(CH2)pG, and the three-cognate diphosphates in their interactions with tubulin. We found that pp(CH2)pddG was as active as ddGTP and pp(CH2)pG in supporting formation of polymer of increased stability, but that its affinity for the exchangeable site was lower than that of both singly modified analogs [relative affinities for the exchangeable site for pp(CH2)pddG:ddGTP:pp(CH2)-pG:GTP were 1:2.8:10:273]. There were significant differences in interactions of each of the three analogs with tubulin, and the behavior of pp(CH2)pddG was intermediate between that of ddGTP and that of pp(CH2)pG. Most importantly, under the reaction conditions studied, with heat-treated microtubule-associated proteins (MAPs) ddGTP-induced polymer consisted of short microtubules, while polymer formed with both pp(CH2)pddG and pp(CH2)pG consisted of short sheets. On the other hand, assembly without MAPs had a fivefold lower critical concentration for tubulin with ddGTP and pp(CH2)pddG (0.5 mg/ml) than with pp(CH2)pG (2.5 mg/ml). De novo assembly, which occurs readily with 2',3'-dideoxyguanosine 5'-diphosphate, was not observed with either alpha, beta-methylenediphosphate GDP analog.

Antineoplastic Agents↗
PubMed1987

Guanosine triphosphate cyclohydrolase I deficiency: early diagnosis by routine urine pteridine screening.

A deficiency of hepatic guanosine triphosphate cyclohydrolase I is reported in a 4-month-old infant in whom positive results on a Guthrie phenylketonuria test in the neonatal period were found. Because of the significantly elevated serum phenylalanine levels a diagnosis of classical phenylketonuria was made, and dietary therapy was started. Urinary pteridine screening for cofactor variants, however, revealed extremely low levels of both neopterin and biopterin. This suggested the possibility of guanosine triphosphate cyclohydrolase I deficiency and led to additional confirmatory assays. Repeat urine, serum, and CSF pteridine profiles, combined with tetrahydrobiopterin-loading studies and the assay of guanosine triphosphate cyclohydrolase I activity in a liver biopsy, confirmed the defect. It is significant to note that the diagnosis was made before the onset of major clinical symptoms. This case illustrates the need for routine cofactor variant screening of all infants in whom hyperphenylalaninemia is diagnosed in the neonatal period.

Aminohydrolases↗
PubMed1988

Regulation of guinea pig myometrial beta-adrenoreceptors by guanosine triphosphate and magnesium ion.

The effects of guanosine triphosphate (GTP) and magnesium on the interaction of 1-isoproterenol with beta-adrenoreceptors were studied in myometrial membranes from nonpregnant and late-pregnant (0.9 gestation, term 65 days) guinea pigs. The affinity of the beta-adrenoreceptor for 1-isoproterenol, as measured by inhibition of (-)125I-cyanopindolol binding, was increased by 10 mM MgCl2. The addition of 250 microM GTP reversed this process. In the presence of MgCl2, the competition curves could be resolved into two affinity states of the beta-adrenoreceptor, high and low, respectively. The ratio of the dissociation constant of the high-affinity state to that of the low-affinity state was significantly higher in late-pregnant than in the nonpregnant animals. In the presence of GTP, there was only one (low-affinity) state of the receptor detectable. In both groups of animals, the interaction between beta-adrenoreceptor agonists and myometrial beta-adrenoreceptors was positively modulated by MgCl2. This process was reversed by GTP. However, there appeared to be a differential regulation of the ability of the myometrial beta-adrenoreceptor to form a high-affinity state, depending on the reproductive state of the animal.

Animals↗