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 883 records · Page 49Linked to original sources
PubMed1984

Randomized controlled trial of adenine arabinoside monophosphate for chronic type B hepatitis.

Twenty patients with chronic type B hepatitis were entered into a randomized, controlled study of adenine arabinoside monophosphate. Before entry, all patients were documented to have stable levels of hepatitis B surface antigen, hepatitis B e antigen, serum hepatitis B virus deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity. Ten patients received adenine arabinoside monophosphate and 10 received no treatment. The two groups were well matched with respect to age, sex, known duration of hepatitis B surface antigen, presence of symptoms, serum aminotransferase levels, and hepatic histopathology. During the 4 wk of therapy, serum levels of hepatitis B virus fell dramatically. However, serum hepatitis B virus-deoxynbonucleic acid or deoxyribonucleic acid polymerase activity, or both, remained detectable, and levels of hepatitis B virus invariably rose once therapy was stopped. From 2 to 9 mo after therapy, 4 of the 10 treated patients became hepatitis B e antigen or hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase negative, or both, and the results of routine serum biochemical tests improved. However, 2 of these 4 patients later relapsed. In the control group, 2 patients became seronegative for hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase and manifested improvement in serum biochemical results by 18-24 mo after randomization. Thus, long-term improvements in clinical and serologic features of disease occurred in 20% of both treated and control patients. Side effects of adenine arabinoside monophosphate therapy were common, and 3 patients developed a severe and prolonged neuropathic pain syndrome. These results suggest that a 4-wk course of adenine arabinoside monophosphate therapy does not induce an increased rate of long-term remissions in chronic type B hepatitis.

Adult↗
PubMed1983

Creatine kinase of heart mitochondria: no changes in its kinetic properties after inhibition of the adenine nucleotide translocator.

The kinetic properties of heart mitochondrial creatine kinase were measured with and without inhibitors of the adenine nucleotide translocator. No significant differences were observed suggesting that mitochondrial creatine kinase is not acting together with the adenine nucleotide translocator as a functional multienzyme complex. Adenine nucleotides from the bulk phase are able to enter the active center of creatine kinase without the necessity of transport via the adenine nucleotide translocator.

Animals↗
PubMed1977

Reversible inhibition of adenine nucleotide translocation by long chain acyl-CoA esters in bovine heart mitochondria and inverted submitochondrial particles. Comparison with atractylate and bongkrekic acid.

Isolated beef heart mitochondria incubated with atractylate and oleoyl coenzyme A at concentrations below 5 micrometer produced an immediate and significant inhibition of adenine nucleotide translocation, whereas inhibition by bongkrekic acid, which required preincubation with the mitochondria, was less rapid and a concentration of 50 micrometer was required for maximum effect. In sonicated submitochondrial particles, which are inverted with the inner face of the membrane exposed, the adenine nucleotide translocase was much more sensitive to inhibition by bongkrekic acid but was now insensitive to atractylate. The characteristics of the inhibition of the adenine nucleotide translocase by oleoyl-CoA were similar qualitatively and quantitatively in isolated mitochondria and "inside out" submitochondrial particles. Thus, in contrast to both atractylate and bongkrekic acid which bind to the membrane asymmetrically, long chain acyl-CoA esters have the capacity to bind and inhibit the adenine nucleotide translocase from both sides of the inner mitochondrial membrane.

Adenosine Triphosphate↗
PubMed1994

A mutational analysis of the two motifs common to adenine methyltransferases.

All methyltransferases that use S-adenosyl methionine as the methyl group donor contain a sequence similar to (D/E/S)XFXGXG which has been postulated to form part of the cofactor binding site. In N6-adenine DNA methyltransferases there is a second motif, (D/N)PP(Y/F), which has been proposed to play a role similar to the catalytically essential PC motif conserved in all C5-cytosine DNA methyltransferases. We have made a series of amino acid changes in these two motifs in the EcoKI N6-adenine DNA methyltransferase. The mutant enzymes have been purified to homogeneity and characterized by physical biochemical methods. The first G is the most conserved residue in motif I. Changing this G to D completely abolished S-adenosyl methionine binding, but left enzyme structure and DNA target recognition unaltered, thus documenting the S-adenosyl methionine binding function of motif I in N6-adenine methyltransferases. Substitution of the N with D, or F with either G or C, in motif II abolished enzyme activity, but left S-adenosyl methionine and DNA binding unaltered. Changes of F to Y or W resulted in partial enzyme activity, implying that an aromatic residue is important for methylation. The substitution of W for F greatly enhanced UV-induced cross-linking between the enzyme and S-adenosyl methionine, suggesting that the aromatic residue is close in space to the methyl-group donor.

Adenine↗
PubMed1994

Selective determination of adenine-containing compounds by capillary electrophoresis with laser-induced fluorescence detection.

Capillary electrophoresis coupled with laser-induced fluorescence detection provides a selective analysis of mixtures of adenine-containing compounds (adenine, adenosine, cAMP, AMP, ADP, and ATP) that are derivatized using chloroacetaldehyde as a fluorogenic reagent. The components can be detected with linear response over the concentration range of 10(-4) to 10(-9) M, and the detection limit corresponds to 5 to 10 x 10(-19) mol for each nucleotide. Analysis is achieved in less than 10 min with high separation efficiencies (up to 400,000 theoretical plates) and shows good reproducibility for migration times (0.5 to 1.0%) and peak heights (2.8 to 7.7%). To demonstrate the rapid analysis of small-volume samples, the adenine-containing compounds present in an oocyte from Xenopus laevis are determined.

Adenine↗
PubMed1977

Effect of triiodothyronine on the biosynthesis of adenine nucleotides and proteins in the rat heart.

1) During the development of myocardial hypertrophy induced by 3,3',5-triiodo-L-thyronine the enhancement of de novo synthesis of adenine nucleotides occurs very early and precedes the increase of protein synthesis. In this respect there is a striking parallelism with other types of cardiac hypertrophy. 2) The acceleration of adenine nucleotide synthesis under these experimental conditions seems to be due to a greater availability of cardiac 5-phosphoribosyl-1-pyrophosphate. 3) The triiodothyronine-induced enhancement of adenine nucleotide synthesis can be attenuated by beta-receptor-blocking agents.

Adenine↗
PubMed1981

Characterization of the biochemical basis of a complete deficiency of the adenine phosphoribosyl transferase (APRT).

In order to study the biochemical basis of a complete deficiency of adenine phosphoribosyl transferase (APRT) the enzyme was purified to homogeneity, its properties were characterized, and antibodies raised. The enzyme is indirectly involved in adenine uptake. Apparently, by forming AMP the internal concentration of adenine is kept low allowing it diffusion. The same APRT is present in various tissues as was revealed by antibody inactivations employing anti-erythrocyte APRT as well as by direct enzyme assays in cells from the APRT deficient patient. In vitro cultured fibroblasts derived from this patient had less than 0.02% enzyme activity. No cross-reacting material was found in erythrocytes obtained from an APRT deficient child.

Adenine↗
PubMed1975

A potent depressant action of adenine derivatives on cerebral cortical neurones.

Adenosine and several adenine nucleotides depress the excitability of cerebral cortical neurones, including identified Betz cells. Cyclic 3',5'-adenosine monophosphate was a less effective depressant than various other adenine nucleotides, including cyclic 2',3'-adenosine monophosphate. Adenine and inosine had only weak depressant activity. An initial excitant action of ATP was observed on several neurones. This was succeeded by a depressant effect when the application of ATP was terminated.

Adenine↗
PubMed1984

Sensitive fluorimetry of adenine-containing compounds with high-performance liquid chromatography.

A definitive method to determine adenine compounds simultaneously was established by introducing a new fluorescent reagent into high-performance liquid chromatography. Bromoacetaldehyde was the best reagent among the haloacetaldehydes examined. A quantitative reaction was obtained even for unstable ADP and ATP. A high resolution of adenine nucleotides was obtained using a column of Hitachi gel No. 3012-N. The method was applied to the measurement of cyclic AMP in urine, and ADP and ATP in brain and blood. Further, the sensitivity of the method was increased by a new fluorescence spectrophotometer constructed for micro-HPLC. Femtomole amounts of the adenine nucleotides were clearly separated.

Acetaldehyde↗
PubMed1983

Complete deficiency of adenine phosphoribosyl transferase: report of a new family.

We report a case of 2,8-dihydroxyadenine urinary lithiasis with complete deficiency of adenine phosphoribosyl transferase. Adenine phosphoribosyl transferase activities in the erythrocytes, lymphocytes and granulocytes of the patient's family also were determined. The propositus and her younger brother were homozygotes for adenine phosphoribosyl transferase deficiency and her parents were heterozygotes. This is the third family with this disease to be reported.

Adenine↗
PubMed1997

Purification and characterization of adenine phosphoribosyltransferase from Saccharomyces cerevisiae.

Adenine phosphoribosyltransferase (APRT) from Saccharomyces cerevisiae was purified approximately 1500-fold. The enzyme catalyzes the Mg-dependent condensation of adenine and 5-phosphoribosylpyrophosphate (PRPP) to yield AMP. The purification procedure included anion exchange chromatography, chromatofocusing and gel filtration. Elution of the enzyme from the chromatofocusing column indicated a pI value of 4.7. The molecular mass for the native enzyme was 50 kDa; however, upon electrophoresis under denaturing conditions two bands of apparent molecular mass of 29 and 20 kDa were observed. We have previously reported the presence of two separate coding sequences for APRT, APT1 and APT2 in S. cerevisiae. The appearance of two bands under denaturing conditions suggests that, unlike other APRTs, this enzyme could form heterodimers. This may be the basis for substrate specificity differences between this enzyme and other APRTs. Substrate kinetics and product inhibition patterns are consistent with a ping-pong mechanism. The Km for adenine and PRPP were 6 microM and 15 microM, respectively and the Vmax was 15 micromol/min. These kinetic constants are comparable to the constants of APRT from other organisms.

Adenine↗
PubMed2004

Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis.

In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is present in all tissues and provides the only known mechanism for the metabolic salvage of adenine resulting from the polyamine biosynthesis pathway or from dietary sources. In humans, APRT deficiency results in serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA) precipitation in the renal interstitium. To address the molecular basis of DHA-urolithiasis, the recombinant human APRT was crystallized in complex with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction data extended to 2.1 A resolution led to a final crystallographic R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of nine beta-strands and six alpha-helices, and the active site pocket opens slightly to accommodate the AMP product. The core of APRT is similar to that of other phosphoribosyltransferases (PRTases), although the adenine-binding domain is quite different. Structural comparisons between the human APRT and other "type I" PRTases of known structure revealed several important features of the biochemistry of PRTases. We propose that the residues located at positions corresponding to Leu159 and Ala131 in hAPRT are responsible for the base specificities of type I PRTases. The comparative analysis shown here also provides structural information for the mechanism by which mutations in the human APRT lead to DHA-urolithiasis.

Adenine↗
PubMed2006

N6-methyl-adenine: an epigenetic signal for DNA-protein interactions.

N(6)-methyl-adenine is found in the genomes of bacteria, archaea, protists and fungi. Most bacterial DNA adenine methyltransferases are part of restriction-modification systems. Certain groups of Proteobacteria also harbour solitary DNA adenine methyltransferases that provide signals for DNA-protein interactions. In gamma-proteobacteria, Dam methylation regulates chromosome replication, nucleoid segregation, DNA repair, transposition of insertion elements and transcription of specific genes. In Salmonella, Haemophilus, Yersinia and Vibrio species and in pathogenic Escherichia coli, Dam methylation is required for virulence. In alpha-proteobacteria, CcrM methylation regulates the cell cycle in Caulobacter, Rhizobium and Agrobacterium, and has a role in Brucella abortus infection.

Adenine↗
PubMed1965

THE EFFECTS OF ADENINE NUCLEOTIDES ON PYRUVATE METABOLISM IN RAT LIVER.

1. The effects of adenine nucleotides on pyruvate metabolism by isolated liver cells and isolated mitochondria have been investigated. The amount of pyruvate carboxylated has been estimated by determining the tricarboxylic acid-cycle intermediates, glutamate and aspartate accumulating in the incubation medium. The extent of pyruvate oxidation has been assessed by measuring oxygen uptake and the yield of (14)CO(2) from [1-(14)C]pyruvate and [2-(14)C]pyruvate. 2. When catalytic amounts of adenine nucleotides (1-2mm) were added to suspensions of isolated liver cells incubated with pyruvate an ATP:ADP ratio greater than 6:1 was maintained. Both pyruvate oxidation to acetyl-CoA and the oxidation of acetyl-CoA through the tricarboxylic acid cycle were stimulated but pyruvate carboxylation was not affected. The production of acetyl-CoA exceeded the capacity of the cells for the oxidation of acetyl-CoA and the excess was converted into ketone bodies. 3. If a low ATP:ADP ratio was maintained in isolated cells or mitochondria by incubating them with dinitrophenol or hexokinase, pyruvate carboxylation was grossly inhibited, oxygen uptake depressed and ketone-body formation stimulated. Measurement of oxaloacetate concentrations confirmed that under these conditions oxaloacetate was rate-limiting for the oxidation of acetyl-CoA via the tricarboxylic acid cycle. The inclusion in the incubation medium of fumarate (1.25mm) completely prevented the ketogenic action of dinitrophenol or hexokinase. 4. When ADP (5mm) was added to a suspension of isolated liver cells incubated with pyruvate an actual ADP concentration of about 1mm was attained. This brought about effects on pyruvate metabolism similar to those obtained with dinitrophenol or hexokinase. 5. These results support the concept that the relative concentrations of adenine nucleotides within the liver cell may play a role in governing the rates of pyruvate oxidation and carboxylation. In addition, they provide further evidence that the availability of oxaloacetate in the liver cell can play a key role in determining whether acetyl-CoA arising from pyruvate is oxidized through the tricarboxylic acid cycle or converted into ketone bodies.

Acetoacetates↗
PubMed1971

The limitation of glycolysis in adenine-deficient Escherichia coli.

1. In many instances, there was no change in the rate of oxygen consumption per cell when adenine was withdrawn from purine auxotrophs of Escherichia coli and Salmonella typhimurium. 2. However, adenine deficiency inhibited the metabolism of glucose, mannitol or glycerol in a purA(-) strain, in purB(-) or purH(-) strains in the absence of histidine and in purB(-) mutants supplied with hypoxanthine. These are all instances where reactions occur to consume adenine nucleotides. 3. The inhibition of glucose oxidation is accompanied by the accumulation of fructose 1,6-diphosphate and dihydroxyacetone phosphate. 4. Insufficiency of ADP for phosphoglycerate kinase is the most probable cause of the inhibition.

Acetone↗
PubMed1986

Stimulation of glycogenolysis by adenine nucleotides in the perfused rat liver.

Infusion of adenine nucleotides and adenosine into perfused rat livers resulted in stimulation of hepatic glycogenolysis, transient increases in the effluent perfusate [3-hydroxybutyrate]/[acetoacetate] ratio, and increased portal vein pressure. In livers perfused with buffer containing 50 microM-Ca2+, transient efflux of Ca2+ was seen on stimulation of the liver with adenine nucleotides or adenosine. ADP was the most potent of the nucleotides, stimulating glucose output at concentrations as low as 0.15 microM, with half-maximal stimulation at approx. 1 microM, and ATP was slightly less potent, half-maximal stimulation requiring 4 microM-ATP. AMP and adenosine were much less effective, doses giving half-maximal stimulation being 40 and 20 microM respectively. Non-hydrolysed ATP analogues were much less effective than ATP in promoting changes in hepatic metabolism. ITP, GTP and GDP caused similar changes in hepatic metabolism to ATP, but were 10-20 times less potent than ATP. In livers perfused at low (7 microM) Ca2+, infusion of phenylephrine before ATP desensitized hepatic responses to ATP. Repeated infusions of ATP in such low-Ca2+-perfused livers caused homologous desensitization of ATP responses, and also desensitized subsequent Ca2+-dependent responses to phenylephrine. A short infusion of Ca2+ (1.25 mM) after phenylephrine infusion restored subsequent responses to ATP, indicating that, during perfusion with buffer containing 7 microM-Ca2+, ATP and phenylephrine deplete the same pool of intracellular Ca2+, which can be rapidly replenished in the presence of extracellular Ca2+. Measurement of cyclic AMP in freeze-clamped liver tissue demonstrated that adenosine (150 microM) significantly increased hepatic cyclic AMP, whereas ATP (15 microM) was without effect. It is concluded that ATP and ADP stimulate hepatic glycogenolysis via P2-purinergic receptors, through a Ca2+-dependent mechanism similar to that in alpha-adrenergic stimulation of hepatic tissue. However, adenosine stimulates glycogenolysis via P1-purinoreceptors and/or uptake into the cell, at least partially through a mechanism involving increase in cyclic AMP. Further, the hepatic response to adenine nucleotides may be significant in regulating hepatic glucose output in physiological and pathophysiological states.

Adenine↗
PubMed1990

Cleavage of the bacteriophage P1 packaging site (pac) is regulated by adenine methylation.

The packaging of bacteriophage PI DNA is initiated when the phage packaging site (pac) is recognized and cleaved and continues until the phage head is full. We have previously shown that pac is a 162-base-pair segment of P1 DNA that contains seven DNA adenine methyltransferase methylation sites (5'-GATC). We show here that cleavage of pac is methylation sensitive. Both in vivo and in vitro experiments indicate that methylated pac is cleavable, whereas unmethylated pac is not. Moreover, DNA isolated from P1 phage and containing an uncut pac site was a poor substrate for in vitro cleavage until it was methylated by the Escherichia coli DNA adenine methyltransferase. Comparison of that uncut pac DNA with other viral DNA fragments by digestion with methylation-sensitive restriction enzymes indicated that the uncut pac DNA was preferentially undermethylated. In contrast, virion DNA containing a cut pac site was not undermethylated. We believe these results indicate that pac cleavage is regulated by adenine methylation during the phage lytic cycle.

Adenine↗
PubMed1996

Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis.

Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis.

Adenine↗