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PubMed1968

Biochemical energetics of simulated platelet plug formation. Effect of thrombin, adenosine diphosphate, and epinephrine on intra- and extracellular adenine nucleotide kinetics.

Washed human platelets were incubated in a modified Ringer's solution, pH 7.1, at 37 degrees C for 1 hr. Intracellular basal levels for glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and orthophosphate were 31.1, 2.52, 1.39, 0.36, and 1.2 mumoles/ml of platelets, respectively. Extracellular ATP, ADP, and AMP remained fairly constant and represented 4, 2, and 4% of total adenine nucleotide content. Total adenine nucleotide content remained unchanged during the period of control incubation. Glycogen depletion was 17.8 mumoles/ml at the end of 1 hr; lactate production was 20.7 mumoles/ml per hr. In the presence of glucose, lactate production increased 100%, and glycogen depletion was spared 13%. Approximately 55% of glucose or glycogen fuel was converted to lactate. The agglutinating agents, thrombin, ADP, and epinephrine, resulted in increased glycogen depletion and lactate production both in the presence and absence of glucose. The effect of thrombin was greater than epinephrine. The effect of epinephrine was greater than ADP. All three agglutinating agents resulted in loss of high energy phosphates (net decline in adenine nucleotides) with release of adenine nucleotides into the extracellular environment. The effect of thrombin was greater than ADP. The effect of ADP was greater than epinephrine. In experiments with ADP addition, significant quantities of ADP were converted to AMP extracellularly. In experiments with thrombin and epinephrine appreciable quantities of extracellular orthophosphate were taken up by plateletes and could not be accounted for by changes in intracellular orthophosphate or adenine nucleotide. Sufficient ADP was released during exposure to thrombin and epinephrine to account for platelet agglutination. Changes in intracellular adenine nucleotides and orthophosphate could be correlated with the activation of regulator glycogenolytic and glycolytic enzymes.

Adenine Nucleotides↗

PubMed1981

Increased adenine nucleotide turnover in duchenne muscular dystrophy.

To investigate a possible disorder of adenine nucleotide turnover in Duchenne muscular dystrophy, we evaluated 15 patients with mild Duchenne muscular dystrophy, eight patients with severe muscular dystrophy, seven patients with other neuromuscular disorders, and eight patients with hypogammaglobulinemia but no muscle disease. The serum urate concentration was similar in all four groups. Base line urinary purine excretion was elevated in all patients with neuromuscular disease with values of 1.72 +/- 0.15, 2.37 +/- 0.22, 2.49 +/- 0.35, and 2.60 +/- 0.48 mumoles/100 ml glomerular filtration for control subjects, mild Duchenne muscular dystrophy, severe disease, and other neuromuscular diseases, respectively. Adenine nucleotide pool turnover was measured by labeling with [8-14C]adenine and then 5 days later administering intravenous fructose. Five-day cumulative mean radioactivity excretion was elevated in mild and severe Duchenne muscular dystrophy with excretion values of 11.4 +/- 0.7 and 11.5 +/- 1.1% of administered radioactivity, respectively, as compared to 9.0 +/- 0.9% of administered radioactivity for control subjects. After intravenous fructose infusion, patients with Duchenne muscular dystrophy had a less than normal rise in serum urate concentration, a normal increase of urinary urinary purine excretion, and a greater than normal elevation of urinary radioactivity excretion and urinary purine specific activity. Patients with other neuromuscular diseases had virtually no rise in plasma urate concentration, less than normal increase in urinary total purine excretion, and a greater than normal increase of urinary radioactivity excretion and urinary specific activity. These observations suggest that there is an increased rate of adenine nucleotide turnover in Duchenne muscular dystrophy. In patients with other neuromuscular disease an increased rate of adenine nucleotide turnover resembled the abnormality expected from a diminished adenine nucleotide pool.

Adenine Nucleotides↗

PubMedDate not supplied

Adenine nucleotide N-glycosidase activity of the A-chain of cinnamomin characterized by 1H-nuclear magnetic resonance.

Plant ribosome-inactivating proteins specifically cleave an N-glycosidic bond of a unique adenosine in the largest ribosomal RNA, releasing an adenine from ribosomes of different sources. Here, 1H-nuclear magnetic resonance is used to analyze the enzymatic products of the A-chain of cinnamomin, a type-II ribosome-inactivating protein (RIP) acting on the nucleotides in situ. The enzymatic activities of the RIP on nine nucleotides are compared. Cinnamomin A-chain can cleave the N-glycosidic bond and release an adenine base from adenine nucleotides except 5'-ATP; however, it cannot act on 5'-GMP, 5'-CMP, and 5'-UMP. The A-chain in the mixture of cinnamomin A- and B-chain exhibits higher activity toward adenine nucleotides than the A-chain alone does, suggesting that the B-chain can conformationally stabilize the A-chain. Intact cinnamomin also exhibits lower activity toward adenine nucleotides. However, cinnamomin B-chain and heat-denatured intact cinnamomin cannot hydrolyze all the tested nucleotides. We conclude that hydrolysis of the N-C glycosidic bond of nucleotide compounds by cinnamomin A-chain has a base preference, and the negatively charged phosphate group(s) reduces the recognition ability of the A-chain to adenine nucleotide.

Adenine Nucleotides↗

PubMed1989

Adenine uptake cells in the rat kidney with remarks on the expression of Ia antigen.

The patterns of [14C] adenine ([14C]A) incorporation into DNA by proliferative cells in the kidney were studied by the autoradiographic technique. It was revealed that, after 3 daily injections of [14C]A (1 microCi/g body weight each), a portion of the glomerular cells and a few fibroblastoid cells in the cortical intexstitium incorporated [14C]A into DNA to a remarkable extent. Such cells also incorporated [3H]thymidine, but to a lesser extent. The cells which incorporate [14C]A to a particularly great extent (adenine uptake cells) also occur in other tissues. Such cells are confined to a few cell types of either the macrophage or fibroblast or reticulum cell lines. This fact suggests that the adenine uptake cells observed in the glomerulus are also of a similar cell line and most likely mesangial cells. By immunohistochemical examination for Ia antigen, adenine uptake cells are divided into Ia-positive and Ia-negative types. The present examination showed that the major portion of adenine uptake cells in the glomerulus are Ia-negative, and it is suggested that these cells are analogous to the Ia-negative macrophages in the lung. This suggestion is supported by the fact that, in the glomerulus, colloidal carbon uptake cells (macrophage-like cells) are present in fairly large numbers. The Ia-positive cells seem to be of the same cell line as the adenine uptake cells that express Ia antigen in other tissues, such as septal fibroblasts in the lung.

Adenine↗

PubMed1977

Adenine metabolism in man. 1. After intravenous and peroral administration.

The basal plasma concentration of adenine and its renal excretion was studied in two men. For its analysis partly new chromatographic techniques were developed. The plasma concentration varied around 70 nmol/l; the renal excretion rate was, as reported earlier by other investigators, around 10 nmol/min. Loadings, intravenously during about 3 h and orally, both with about 30 nmol adenine per kg body mass revealed that most of the adenine was metabolized to nucleotide form. In the experiments with intravenous administration of adenine only about 2% of the given dose appeared in the urine as adenine and somewhat less as the easily precipitable metabolite 2,8-dihydroxyadenine. In the peroral loads, with higher plasma adenine concentrations, the ratios of the renally excreted two compounds were one to a few per cent higher.

Adenine↗

PubMed2001

The effect of sodium fluoride on the adenine nucleotide pool in erythrocytes of Wistar rats.

The effect of sodium fluoride on the content of adenine nucleotides, adenine nucleotide pool and energy potential of erythrocytes was studied in male Wistar rats, depending on the dose and time of exposure. Sodium fluoride was administered for 4 and 8 weeks at 4 or 16 ppm through a gastric tube. The concentration of fluorine in serum, ATP, ADP and AMP content in blood and erythrocytes, adenine nucleotide pool and energy potential of erythrocytes were calculated. The results were expressed in SI units and compared statistically with Student's t-test (Statgraphics v. 5.0 software). A significant reduction in the content of ATP and ADP and an increase in the content of AMP in erythrocytes was found after 4 weeks of exposure to 4 or 16 ppm NaF. The adenine nucleotide pool and energy potential were reduced with the smaller dose. After 8 weeks, the ADP content remained significantly reduced with the smaller dose, while the greater dose was associated with a higher energy potential of the cells. Correlations between serum concentration of fluorine, content of adenine nucleotides and adenine nucleotide pool in erythrocytes were noted in all study groups.

Adenine Nucleotides↗

PubMed2002

Behavior of adenine in Na-montmorillonite exposed to gamma radiation: implications to chemical evolution studies.

Adenine is an important compound in biological systems, such as genetic and energy utilization processes. Adenine is readily formed in prebiotic conditions. Its synthesis and stability in environmental conditions are of paramount importance in chemical evolution processes. Clay minerals might have played an important role in the early Earth. Clays are known to have a high affinity for organic compounds, and they may provide protection to adsorbed molecules against high-energy radiation. The purpose of this work is to testthese assumptions. We study the stability of adenine under irradiation, in aqueous solution and also adsorbed in a clay mineral. The recovery of adenine after a gamma irradiation was higher in the system containing clay in relation to a system without clay. Results show that adenine is readily adsorbed in the clay, and that the clay act as surface protector toward the degradation of adenine by the radiation.

Adenine↗

PubMedDate not supplied

Radiation-induced effect of adenine (vitamin B4) on mitomycin C activity. In vitro experiments.

The radiation-induced biological behavior of adenine (vitamin B4) was investigated in vitro under various conditions, implementing breast cancer cells (MCF-7 line) as a model. In aerated media (46% OH and 54% O2*-) at pH=7.4, adenine at low concentration (2 micromol) acted as an efficient radiation-protecting agent. At higher concentration, however, it inhibited cytostatic properties with regard to cancer cells. This double-track activity is based on its chemical structure. Similar features of adenine were also observed in air-free (46% OH, 44% e- aq, 10% H) as well as in media saturated with N2O (90% OH, 10% H), but with different efficiencies. In the presence of mitomycin C (MMC), adenine retained its double-track behavior. Hence, adenine and MMC compete for the e- aq, but the electronically excited adenine molecules can transfer electrons to MMC, leading to the additional formation of active MMC-. By implementation of formate for the conversion of OH and H into the transient *COO-, which subsequently transfers electron to MMC, a highest efficiency of MMC- was obtained.

Adenine↗

PubMed1990

Brief intermittent reperfusion during renal ischemia: effects on adenine nucleotides, oxidant stress, and the severity of renal failure.

The purpose of this study was to assess how brief periods of intermittent reperfusion (IR) imposed during a renal ischemic insult affect adenine nucleotide/catabolite concentrations, oxidant stress, and the severity of ischemic acute renal failure (IARF). Rats were subjected to 35 minutes of renal pedicle occlusion with or without brief IR periods (total less than or equal to 3 minutes). Adenine nucleotides and their catabolites were measured at the end of ischemia and at 30 minutes of the recovery period. Oxidant stress in the recovery phase was assessed by non-protein-bound sulfhydryl and malondialdehyde (MDA) concentrations. The severity of IARF was quantified at 24 hours by degrees of azotemia and histologic damage. Although IR had no significant impact on end-ischemic ATP concentrations, it did induce profound adenine nucleotide catabolite depletion; the sum of adenosine, inosine, inosine monophosphate, hypoxanthine, and xanthine fell by 78%, compared with control ischemia values (p less than 0.001). The pattern of IR affected the degree of catabolite depletion: dividing a single 3-minute IR period into two 1 1/2-minute segments increased catabolite loss by 45% without affecting adenine nucleotide content. Although adenine nucleotide catabolites can be resynthesized to ATP, IR did not worsen postischemic adenine nucleotide recovery. IR augmented postischemic sulfhydryl depletion by 8% (p less than 0.02). However, lipid peroxidation (as assessed by MDA) did not result and the severity of IARF was not adversely affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1986

Control of mitochondrial content of adenine nucleotides by submicromolar calcium concentrations and its relationship to hormonal effects.

Rat liver mitochondria were incubated at 30 degrees C with 4 mM ATP in a medium similar in electrolyte composition to that of hepatic cytosol. Under these conditions, a net increase in mitochondrial adenine nucleotides was observed that was dependent on the concentration of free Ca2+ [( Ca2+]) in the incubation medium. At 0.2 microM [Ca2+] or less, there was no demonstrable uptake of adenine nucleotides; at 0.4 microM [Ca2+], or greater, net uptake occurred. The calcium-dependent accumulation of nucleotides by mitochondria required Mg2+ in the incubation medium and was insensitive to carboxyatractyloside. The uptake of adenine nucleotides was enhanced by the addition of antimycin A or antimycin A together with oligomycin. Accumulation of nucleotides appeared to be associated with a small increase in mean mitochondrial volume, but the membrane potential was not affected. No uptake or loss of NAD-NADH by mitochondria was detected. Ruthenium red failed to inhibit the calcium-dependent uptake of adenine nucleotides by the mitochondria, indicating that stimulation of this process by Ca2+ does not involve transport of the cation into mitochondria by the Ca2+ uniporter. Because glucagon acts to elevate cytosolic [Ca2+] from approximately 0.2 microM to 0.6 microM, the same range affecting nucleotide uptake, it is proposed that the increase in mitochondrial adenine nucleotides that follows treatment with glucagon is mediated by the rise in cytosolic [Ca2+] produced by the hormone. This hypothesis was supported by the observation that epinephrine and A23187, agents that raise cytosolic [Ca2+], increased the content of mitochondrial adenine nucleotides in isolated hepatocytes. Furthermore, cells, incubated under calcium-depleting conditions, had a diminished response to glucagon.

Adenine Nucleotides↗

PubMed1987

Response of the wild type and low xanthine dehydrogenase strains of Drosophila melanogaster to adenine resistance selection.

Survival rates of two Drosophila melanogaster strains, the Oregon R Wild Type (WT), and a mutant that was Low Xanthine Dehydrogenase (LXD), grown for six generations in control and in adenine-supplemented media, were determined. Although adenine was toxic to both strains, it was less toxic to the LXD strain. Uric acid levels indicated that WT Drosophila melanogaster was less able to metabolize adenine through the detoxification pathway. Male flies of both strains appeared to be more susceptible to adenine toxicity than were female. The results demonstrate that the adenine resistant strain may possess an enzyme pattern to minimize the toxic effect of adenine.

Adenine↗

PubMed1985

[Characteristics of adenosine activity on adenine nucleotide metabolism of rat thymocytes].

The effects of adenosine on adenine nucleotide metabolism in [14C]adenine-labeled rat thymocytes were studied. It was shown that adenosine increases the intracellular pool of adenine nucleotides, predominantly ATP, which is accompanied by marked acceleration of their catabolism and a release of labeled products (especially inosine, hypoxanthine and adenosine) from the thymocytes. The effect of adenosine depends on its concentration and manifests itself already at 10(-6) M. 2-Deoxycoformycin partly relieves the effect of adenosine on adenine nucleotide metabolism. Exogenous deoxyadenosine, inosine, hypoxanthine and adenine, unlike adenosine, do not significantly affect the adenine nucleotide catabolism and the label release from the cells. All the effectors under study strongly increase inosine transport from the thymocytes, and inhibit, with the exception of adenosine, the hypoxanthine release from the cells.

Adenine Nucleotides↗

PubMed1985

Effects of inosine on cardiac adenine nucleotide metabolism in rats.

Inosine was administered as a continuous intravenous infusion (100 mg/kg per hr) in rats treated with isoproterenol (25 mg/kg, s.c.). After 24 hr, the isoproterenol-induced decline in myocardial ATP and total adenine nucleotides was attenuated by inosine. Infusion of ribose (100 mg/kg per hr) had a similar cardioprotective influence. The effect of inosine may have been due to the incorporation into cardiac adenine nucleotides of the degradation products of inosine, either of the ribose moiety via the de novo synthesis pathway or of hypoxanthine via the salvage pathway utilizing 5-phosphoribosyl-1-pyrophosphate. To decide this, [8-(14)C]inosine was injected intravenously 4 hr after administration of isoproterenol. Its incorporation into myocardial adenine nucleotides was enhanced. Furthermore, the effect of inosine on the de novo synthesis of adenine nucleotides in normal and isoproterenol-stimulated hearts was studied and compared to that of ribose. The normal rate was attenuated and the isoproterenol-elicited increase was reduced by inosine. In contrast, ribose stimulated adenine nucleotide biosynthesis in the control rat heart and potentiated the isoproterenol-induced enhancement. These results indicate that the effect of inosine is not due to the metabolism of ribose-1-phosphate via the pentose phosphate and the de novo synthesis pathways, but rather to the 5-phosphoribosyl-1-pyrophosphate-dependent salvage of hypoxanthine. Obviously, this pathway is of such a magnitude that the isoproterenol-evoked decline in myocardial adenine nucleotide levels is attenuated.

Adenine Nucleotides↗

PubMed1979

Adenine cycle in hepatopancreocytes of Helix pomatia (Gastropoda).

Intact hepatopancreocytes were obtained from hibernating or active purinotelic snails, H. pomatia (Gastropoda). When incubated with [14C]glycine or [14C]formate, they synthesized de novo purine compounds, including also adenylates, adenosine and adenine. Hepatopancreocytes resynthesized also adenylates and other purine compounds from [3H]adenine or from [3H]adenosine split by the H. pomatia cell enzyme to adenine; the resynthesis of ADP+ATP was proportional to adenine concentration. Thus all reactions of the postulated adenine cycle: AMP leads to adenosine leads to adenine leads to AMP occur in the intact hepatopancreocytes; this cycle could probably be responsible for maintenance of the high level of adenylates during winter sleep.

Adenine↗

PubMedDate not supplied

[Adenine effect on the biosynthesis of 5'-inosinic acid by the mutant Brevibacterium ammoniagenes 225-5].

The effect of a temperature rise from 28 to 37 degrees C on the biosynthesis of 5'-inosine acid (IMP) by the mutant Brevibacterium ammoniagenes 225-5 was studied. The inhibitory effect of increased temperature on the IMP biosynthesis was dependent on the adenine concentration. The study of IMP synthesis on the media with different adenine concentrations showed that adenine controlled not only the synthesis of purines de novo but also, to a larger extent, so-called salvage IMP synthesis from hypoxanthine. The effect of increased temperature was identical to that of excessive adenine. Temperature rise as well as increase in adenine concentration intensified metabolic processes (increased the level of glucose consumption and the rate of nucleic acid synthesis) and restored in part cell permeability. This was indicated by the release of protein and ribose-5-phosphate into the culture fluid, and by the change in cell morphology. An optimal adenine concentration may be altered either way in response to the changes in other fermentation conditions, i.e. inoculum amount, aeration, and addition of histidine.

Adenine↗

PubMed1997

[Deamination of adenine and adenosine in staphylococci].

Deaminations of adenine and adenosine by pattern strains of 24 staphylococcal species, were tested. During 3 hours of incubation of the suspensions of 8 staphylococci with adenine the liberation of ammonia occurred. The same staphylococci accumulated ammonia in the incubation medium with adenosine. The Staphylococcus intermedius PCM 2405 strain as opposite to the Staphylococcus aureus 536 strain in the media with adenine or adenosine accumulated hypoxanthine or inosine, respectively and ammonia. These results indicated that adenine deaminase (adenase) and adenosine deaminase activities were associated with the cells of the Staphylococcus intermedius PCM 2405 strain. Staphylococci were heterogeneous within three species groups with respect to adenine and adenosine deaminations. Adenine and adenosine determinations were absent in staphylococci belonging to the Staphylococcus simulans species group.

Adenine↗

PubMed1992

Contrast in adenine uptake by chicken and rabbit erythrocytes in vitro.

1. Relative to rabbit erythrocytes, chicken red blood cells exhibit a much greater capacity to utilize [3H]adenine for nucleotide synthesis in vitro, even at 5 degrees C and in the absence of added inorganic phosphate. 2. This difference is largely due to a higher concentration of phosphoribosylpyrophosphate and greater activity of adenine phosphoribosyltransferase in the avian cells. 3. The capacity of avian erythrocytes for utilization of guanine and hypoxanthine is several fold less than that of adenine. 4. The data are consistent with lower activity for hypoxanthine/guanine phosphoribosyltransferase than for adenine phosphoribosyltransferase in intact chicken erythrocytes. 5. The results indicate that reutilization of adenine by chicken erythrocytes may be physiologically significant.

Adenine↗

PubMedDate not supplied

A randomized study of the effects of adenine arabinoside 5'-monophosphate (short or long courses) and lymphoblastoid interferon on hepatitis B virus replication.

A previous randomized controlled study has shown a 30% rate of HBe antigen/antibody seroconversion within 1 year of a month course of adenine arabinoside-5'-monophosphate; no seroconversion occurred in the control group. In this study of patients derived from the same population, 45 hepatitis B virus carriers with chronic liver disease were randomized to receive either a short (4-week) course of adenine arabinoside-5'-monophosphate, a long (7 to 8-week) course of adenine arabinoside-5'-monophosphate or a 12-week course of lymphoblastoid interferon. Long-lasting suppression of hepatitis B virus replication with disappearance of serum hepatitis B virus DNA and clearance of HBeAg occurred within 12 months of treatment in four patients who received the short course of adenine arabinoside-5'-monophosphate and in five who received interferon. Of the nine responders, four also lost HBsAg. A response to antiviral therapy was accompanied by clinical and biochemical evidence of improvement in liver disease. None of the patients who received a long course of adenine arabinoside-5'-monophosphate responded. Peripheral neuropathy and myalgia were the most serious adverse effect affecting three recipients of the short course of adenine arabinoside-5'-monophosphate and eight recipients of the long course. Thrice weekly administration of interferon was well-tolerated. Further studies to identify the characteristics of the "responder patients" and large-scale controlled trials of antiviral therapy in these subgroups are indicated.

Adult↗