Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ADENINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2005

Development of a simple and efficient method for assaying cytidine monophosphate sialic acid synthetase activity using an enzymatic reduced nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide converting system.

A new reliable method to assay the activity of cytidine monophosphate sialic acid (CMP-Sia) synthetase (CSS) has been developed. The activation of sialic acids (Sia) to CMP-Sia is a prerequisite for the de novo synthesis of sialoglycoconjugates. In vertebrates, CSS has been cloned from human, mouse, and rainbow trout, and the crystal structure has been resolved for the mouse enzyme. The mouse and rainbow trout enzyme have been compared with respect to substrate specificity, demonstrating that the mouse enzyme exhibits a pronounced specificity for N-acetylneuraminic acid (Neu5Ac), while the rainbow trout CSS is equally active with either of three Sia species, Neu5Ac, N-glycolylneuraminic acid (Neu5Gc), and deaminoneuraminic acid (KDN). However, molecular details that explain the pronounced substrate specificities are unknown. Understanding the catalytic mechanisms of these enzymes is of major importance, since CSSs play crucial roles in cellular sialylation patterns and thus are potential drug targets in a number of pathophysiological situations. The availability of the cDNAs and the obtained structural data enable rational approaches; however, these efforts are limited by the lack of a reliable high-throughput assay system. Here we describe a new assay system that allows product quantification in a reduced nicotinamide adenine dinucleotide (NADH)-dependent color reaction. The activation reaction catalyzed by CSS, CTP+Sia-->CMP-Sia+pyrophosphate, was evaluated by a consumption of Sia, which corresponds to that of NADH on the following two successive reactions: (i) Sia-->pyruvate+ManNAc (or Man), catalyzed by a sialic acid lyase (SAL), and (ii) pyruvate+NADH-->lactate+oxidized nicotinamide adenine dinucleotide (NAD+), catalyzed by a lactate dehydrogenase (LDH). Consumption of NADH can be photometrically monitored on a microtiter plate reader for a number of test samples at the same time. Furthermore, based on the quantification of CSS used in the SAL/LDH assay, relative activities toward Sia derivatives have been obtained. The preference of mouse CSS toward Neu5Ac and the ability of the rainbow trout enzyme to activate both KDN and Neu5Ac were confirmed. Thus, this simple and time-saving method is suitable for a systematic comparison of enzyme activity of structurally mutated enzymes based on the relative specific activity.

Animals↗
PubMed1979

Preparation of the enantiomeric forms of 9-(5-deoxy-alpha-threo-pent-4-enofuranosyl)adenine and 9-(3,5-dideoxy-beta-D-glycero-pent-4-enofuranosyl)adenine and in vitro antileukemic screening.

The preparation and use of 5-deoxy-5-iodo-1,2-O-isopropylidene-alpha-D-xylofuranose and 5-deoxy-5-iodo-1,2-O-isopropylidene-alpha-D-arabinofuranose in the synthesis of the L and D forms of 9-(5-deoxy-alpha-threo-pent-4-enofuranosyl)adenine, respectively, are described. The preparation of 9-(3,5-dideoxy-beta-D-glycero-pent-4-enofuranosyl)adenine (19) was accomplished from either 3,5-dideoxy-5-iodo-1,2-O-isopropylidene-alpha-D-erythro-pentofuranose or 3,5-dideoxy-5-iodo-1,2-O-isopropylidene-beta-L-threo-pentofuranose. In each case, acetolysis was performed to obtain the acetates which were condensed with 6-(benzamidochloromercuri)purine by the titanium tetrachloride method. Treatment with 1,5-diazabicyclo[5.4.0]undec-5-ene and removal of the blocking groups produced the desired nucleosides. Only 19 showed inhibitory activity toward leukemia L1210 in vitro.

Animals↗
PubMed1981

Syntheses of all singly labeled [N]adenines: Mass spectral fragmentation of adenine.

Syntheses of all five of the singly labeled [(15)N]adenines are now provided. The presence or absence of two-bond (15)N-(1)H spin couplings in their (1)H NMR spectra confirm the location of the isotope in each case. The fragmentation patterns in their mass spectra are indicative of the sequential losses of HCN units and of CH(2)N(2) from adenine upon electron impact.

Journal Article↗
PubMed1977

Genital Herpesvirus homonis infection in mice. II. Treatment with phosphonoacetic acid, adenine arabinoside, and adenine arabinoside 5'-monophosphate.

Genital infection of mice with Herpesvirus hominis type 2 provides an experimental model for screening potential antiviral chemotherapeutic agents before clinical trials in humans. Intravaginal treatment with phosphonoacetic acid (at a dose of 500 mg/kg in saline or as a 5% cream) initiated 3 hr after inoculation with H. hominis type 2 completely inhibited viral replication in the genital tract and prevented subsequent mortality. Although therapy initiated 24-72 hr after infection significantly reduced titers of virus in vaginal secretions from three- to 100-fold, most mice eventually died of encephalitis. Topical treatment with either adenine arabinoside or adenine arabinoside 5'-monophosphate at a dose of 500 mg/kg in saline or as a 10% cream failed to alter viral replication in the genital tract or to protect the mice from death due to encephalitis. Treatment by the intraperitoneal route with any of these three agents had no effect on local viral replication or final mortality.

Adenosine Monophosphate↗
PubMed1977

Affinity labeling of adenine nucleotide-related enzymes with reactive adenine nucleotide analogs. I. Affinity labeling of glyceraldehyde 3-phosphate dehydrogenase and myokinase with a reactive AMP analog.

Rabbit muscle glyceraldehyde 3-phosphate dehydrogenase (GPD) and myokinase (MK) were rapidly inactivated by a reactive AMP analog, N6-(p-bromoacetaminobenzyl)-AMP, under mild conditions. Complete inactivation was observed when 4 and 0.3 mol of the reagent with respect to enzyme were reacted with GPD and MK, respectively. The inactivation of both enzymes were favored at higher pH and the enzymes were protected by addition of adenine nucleotide substrate. Modified GPD or MK had no affinity for AMP-Sepharose, in contrast to the native enzymes. From these results, the inactivation of GPD and MK by the reactive AMP analog can be regarded as an affinity labeling. The posibility that the present AMP analog may be used as a general affinity labeling reagent for various adenine nucleotide-related enzymes is discussed based on the results obtained.

Adenosine Monophosphate↗
PubMed1977

The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine dinucleotide and pyridine-adenine dinucleotide.

We have studied the binding of the enzymatically active NAD+ analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apoenzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in the isomorphous enzyme-NADH-imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule.

Alcohol Oxidoreductases↗
PubMed1989

Stimulation of endogenous L-dopa biosynthesis--a new principle for the therapy of Parkinson's disease. The clinical effect of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotidephosphate (NADPH).

The coenzyme nicotinamide adenine dinucleotide (NADH) has been used as a novel medication in 161 Parkinson patients in an open label trial. In all but 18 patients (11.2%) an improvement in their disability was observed. 115 patients (71.4%) showed a very good (better than 30%) response, and 28 patients (17.4%) a moderate response up to 30%. The best results were obtained with a dose of 25 to 50 mg every second day by i.v. administration. Concomitantly with the improvement in disability, the urine HVA level increased significantly, indicating a stimulation of endogenous L-DOPA biosynthesis. 8 patients have been treated with nicotinamide adenine dinucleotidephosphate (NADPH), 5 of whom exhibited an improvement in their disability from 35 to 55%. The other 3 showed a moderate response of 20 to 25%. In all these patients an increase in the urine level of HVA was detected, reflecting elevated endogenous L-DOPA production.

Adult↗
PubMed1978

Alteration of mortality and pathogenesis of three experimental Herpesvirus hominis infections of mice with adenine arabinoside 5'-monophosphate, adenine arabinoside, and phosphonoacetic acid.

The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.

Animals↗
PubMed1974

Reduced nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate diaphorase activity in human polymorphonuclear leukocytes.

Total reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activities were examined in human neutrophils. Approximately two-thirds of each enzyme activity was located in the granule fraction with the remainder in the soluble. The activities in a 27,000 x g supernatant from a sonic extract of human polymorphonuclear leukocytes were characterized. Both NADH and NADPH diaphorase were insensitive to cyanide and azide and showed greater activity at acid pH. K(m) values for nitroblue tetrazolium were not markedly different (33 muM with NADH and 12 muM with NADPH), but there was a 40-fold difference in K(m) for the reduced pyridine nucleotides (10 muM with NADH and 400 muM for NADPH). Since the intracellular concentration of both nucleotides is estimated to be about 50 muM, it is much more likely, from a kinetic argument, that the respiratory burst of phagocytosis is intiated by the oxidation of NADH rather than of NADPH.

Azides↗
PubMed1973

Regulation of the nicotinamide adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenases of Saccharomyces cerevisiae.

Saccharomyces cerevisiae contains two distinct l-glutamate dehydrogenases. These enzymes are affected in a reciprocal fashion by growth on ammonia or dicarboxylic amino acids as the nitrogen source. The specific activity of the nicotinamide adenine dinucleotide phosphate (NADP) (anabolic) enzyme is highest in ammonia-grown cells and is reduced in cells grown on glutamate or aspartate. Conversely, the specific activity of the nicotinamide adenine dinucleotide (NAD) (catabolic) glutamate dehydrogenase is highest in cells grown on glutamate or aspartate and is much lower in cells grown on ammonia. The specific activity of both enzymes is very low in nitrogen-starved yeast. Addition of the ammonia analogue methylamine to the growth medium reduces the specific activity of the NAD-dependent enzyme and increases the specific activity of the NADP-dependent enzyme.

Amino Acids↗
PubMed2006

Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase.

Three methylated bases, 5-methylcytosine, N4-methylcytosine and N6-methyladenine (m6A), can be found in DNA. However, to date, only 5-methylcytosine has been detected in mammalian genomes. To reinvestigate the presence of m6A in mammalian DNA, we used a highly sensitive method capable of detecting one N6-methyldeoxyadenosine per million nucleosides. Our results suggest that the total mouse genome contains, if any, less than 10(3) m6A. Experiments were next performed on PRED28, a putative mammalian N6-DNA methyltransferase. The murine PRED28 encodes two alternatively spliced RNA. However, although recombinant PRED28 proteins are found in the nucleus, no evidence for an adenine-methyltransferase activity was detected.

Adenine↗
PubMedDate not supplied

[Metabolic mechanism of adenine nucleotide synthesis from exogenous adenine in corynebacteria].

The purpose of this work was to study the activity of the key enzymes of intermediate metabolism in cultures belonging to several genera of coryneform bacteria, either capable or incapable of producing adenylic nucleotides from exogenous adenine. The results are indicative of an increase in the activity of polyphosphate-dependent hexokinase by the stationary growth phase in corynebacteria; in contrast, the activity of the enzyme in coryneform bacteria (rhodococci) remained unchanged. The absence of transketolase activity in the producing strains seems to account for the overproduction of ribose-5-phosphate.

Actinomycetales↗
PubMed1997

Branch-site selection in a group II intron mediated by active recognition of the adenine amino group and steric exclusion of non-adenine functionalities.

The 2'-hydroxyl on a specific bulged adenosine is the nucleophile during the first step of splicing by group II introns. To understand the means by which the ribozyme core recognizes this adenosine, it was mutagenized and effects on catalytic activity were quantified. The results indicate that a low level of mutational variability is tolerated at the branch-site of group II introns, with no apparent loss of fidelity. Analyses of mutant and modified nucleotides at the branch-site reveal that adenine is recognized primarily through the N6 amino group and by steric exclusion of functionalities found on other bases. The mutational and single atom effects reported here contrast with those observed during spliceosomal processing, suggesting that there are important differences in adenosine recognition by the two systems.

Adenine↗
PubMed1988

The amino acid sequence of the eukaryotic DNA [N6-adenine]methyltransferase, M.CviBIII, has regions of similarity with the prokaryotic isoschizomer M.TaqI and other DNA [N6-adenine] methyltransferases.

The sequences of the genes coding for M.CviBIII (from virus NC-1A which infects a eukaryotic alga) [Narva et al., Nucleic Acids Res. 15 (1987) 9807-9823] and M.TaqI (from the bacterium Thermus aquaticus) [Slatko et al., Nucleic Acids Res. 15 (1987) 9781-9796] have been determined recently. Both enzymes methylate adenine in the sequence TCGA. We have compared the predicted amino acid sequences of these two methyltransferases (MTases), with each other and with ten other N6 A-MTases and find regions of similarity. M.CviBIII and M.TaqI were most closely related followed by M.PaeR7, whose recognition sequence (CTCGAG) contains the M.TaqI/M.CviBIII recognition sequence TCGA, and M.PstI, whose recognition sequence is CTGCAG. All of the N6-MTases contain the sequence Asp/Asn-Pro-Pro-Tyr (B-P-P-Y) referred to by Hattman et al. [J. Bacteriol. 164 (1985) 932-937] as region IV. The predicted secondary structure of this region forms a finger-like structure ('beta finger') containing a beta-pleated sheet (...XXXB), two beta-turns (P-P) followed by another beta-pleated sheet [Y/FXXX...].

Amino Acid Sequence↗
PubMed1984

Interaction of fluorescent adenine nucleotide derivatives with the ADP/ATP carrier in mitochondria. 1. Comparison of various 3'-O-ester adenine nucleotide derivatives.

Fluorescent 3'-O-acyl-substituted adenine nucleotide (dimethylamino)naphthoyl and trinitrophenyl groups were studied for binding to the ADP/ATP carrier in mitochondria and submitochondrial particles. The changes in fluorescence intensity and emission maximum are for the most part similar to those observed in nonaqueous solvents. The (dimethylamino)naphthoyl derivatives from a largely quenched aqueous state have a shortwave shift up to 85 nm and increase up to 90-fold (1,5 derivative), whereas the little quenched naphthoyl derivatives show a fluorescence decrease and the weakly fluorescent trinitrophenyl derivative shows only a small increase on binding. All derivatives are good inhibitors (K1 = 1-10 microM) of nucleotide transport. The fluorescence titrations have an apparent K1/2 = 2-7 microM. The fluorescence of the 1,5-DAN nucleotide is fully suppressed by bongkrekate but only partially suppressed by carboxyatractylate. The fluorescence response is much stronger in submitochondrial particles than in mitochondria. Both facts suggest fluorescent binding to the "m" state of the carrier site at the inner face of the membrane. 1,5-DAN-AMP shows a slightly more efficient binding than DAN-ADP or DAN-ATP.

Adenine Nucleotides↗
PubMed1970

Equilibrium relations between the cytoplasmic adenine nucleotide system and nicotinamide-adenine nucleotide system in rat liver.

1. The ratio [ATP]/[ADP][P(i)], as measured by direct determination of the three components in rat liver, was found in various nutritional states to have approximately the same value as the ratio [ATP]/[ADP][P(i)] calculated from the concentrations of lactate, pyruvate, glyceraldehyde phosphate and 3-phosphoglycerate on the assumption that lactate dehydrogenase, glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase are at near-equilibrium in the liver. This implies that the redox state of the NAD couple in the cytoplasm is linked to, and partially controlled by, the phosphorylation state of the adenine nucleotides. 2. The combined equilibrium constant of the glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate kinase reactions at 38 degrees C and I0.25, was found to be 5.9x10(-6). 3. The fall of the [NAD(+)]/[NADH] ratio in starvation and other situations is taken to be the consequence of a primary fall of the [ATP]/[ADP][HPO(4) (2-)] ratio.

Adenine Nucleotides↗
PubMed1970

The binding of dihydronicotinamide--adenine dinucleotide and pyridine-3-aldehyde--adenine dinucleotide by yeast alcohol dehydrogenase.

1. Yeast alcohol dehydrogenase has been found to react with NADH in the presence of acetamide to form a highly fluorescent ternary complex. Titration of the enzyme to form this complex has provided a method for the estimation of the number of binding sites on the enzyme. 2. The binding of NADH by the enzyme has been studied independently, with a modified form of equilibrium dialysis, by using gel filtration. 3. A third method, depending upon the formation of a ternary complex of enzyme, hydroxylamine and pyridine-3-aldehyde-adenine dinucleotide, has also been used to titrate the enzyme. 4. Values obtained with all three methods are substantially in agreement that only three coenzyme-binding sites are available. This is in contrast with the established fact that the enzyme is composed of four identical subunits.

Adenine Nucleotides↗
PubMed2002

Pharmacokinetic and antiretroviral activity in mice of oral [P(1),P(2)-bis[2-(adenin-9-yl)ethoxymethyl]phosphonate], a prodrug of 9-(2-phosphonylmethoxyethyl)adenine.

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is an antiviral drug with activity against herpes viruses, Epstein-Barr virus and retroviruses, including the human immunodeficiency virus. Unfortunately, oral PMEA administration, as required for long-term therapy, is hindered by its low bioavailability. In the present study, the synthesis, oral bioavailability and antiretroviral activity of a new prodrug of PMEA, consisting of two molecules of PMEA bound together by a P-O-P bond (Bis-PMEA), are reported. Pharmacokinetic experiments in mice showed that the oral bioavailabilities of PMEA following oral gavage of Bis-PMEA or PMEA (at a dose equivalent to 28 mg of PMEA/kg) were 50.8 and 13.5%, respectively. These results correlate with the antiviral efficacy of Bis-PMEA administered orally at a dose equivalent to 50 mg/kg of PMEA in C57 BL/6 mice infected with the retroviral complex LP-BM5. Oral treatment with Bis-PMEA proved to be more effective than oral treatment with PMEA given at equimolar doses. Moreover, oral Bis-PMEA was more effective than intraperitoneal PMEA (50 mg/kg) in reducing lymphoadenopathy, hypergammaglobulinaemia and lymph node proviral DNA content, overall in the first weeks post virus inoculation. Bis-PMEA thus appears to be an efficient oral prodrug of PMEA without significant toxicity, at least in this mouse model.

Adenine↗