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PubMed1993

Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training.

The effect of high-intensity intermittent training on the adenine nucleotide content of skeletal muscle was studied. Eleven male subjects (group A) performed high-intensity intermittent training on a cycle ergometer three times per week for 6 wk, followed by 1 wk of the same kind of training with two sessions per day. Nine males (group B) exclusively performed 1 wk of training with two sessions per day. In group A, skeletal muscle total adenine nucleotide (TAN) levels decreased from 25.1 +/- 0.7 (SE) to 22.0 +/- 0.6 mmol/kg dry wt over the 6-wk period (P < 0.01). The subsequent intensive week did not further alter TAN levels. In group B, the intensive week of training reduced TAN levels from 25.1 +/- 0.5 to 19.4 +/- 0.6 mmol/kg dry wt (P < 0.001). The decrease was sustained 72 h after training (P < 0.001). During the intensive week, there was no change in plasma creatine kinase activity in either group A or group B. The plasma activity was, however, higher in group B than in group A on days 4 and 7 of the intensive week (P < 0.05). The results from this study indicate that high-intensity intermittent exercise causes a decrease in resting levels of skeletal muscle adenine nucleotide without a concomitant indication of muscle damage. A training-induced adaptation appears to occur with training by which a further loss of adenine nucleotides is prevented despite an increased training dose.

Adenine Nucleotides↗
PubMed2001

Influence of ribose on adenine salvage after intense muscle contractions.

The influence of ribose supplementation on skeletal muscle adenine salvage rates during recovery from intense contractions and subsequent muscle performance was evaluated using an adult rat perfused hindquarter preparation. Three minutes of tetanic contractions (60 tetani/min) decreased ATP content in the calf muscles by approximately 50% and produced an equimolar increase in IMP. Effective recovery of muscle ATP 1 h after contractions was due to reamination of IMP via the purine nucleotide cycle and was complete in the red gastrocnemius but incomplete in the white gastrocnemius muscle section. Adenine salvage rates in recovering muscle averaged 45 +/- 4, 49 +/- 5, and 30 +/- 3 nmol. h(-1). g(-1) for plantaris, red gastrocnemius, and white gastrocnemius muscle, respectively, which were not different from values in corresponding nonstimulated muscle sections. Adenine salvage rates increased five- to sevenfold by perfusion with approximately 4 mM ribose (212 +/- 17, 192 +/- 9, and 215 +/- 14 nmol. h(-1). g(-1) in resting muscle sections, respectively). These high rates were sustained in recovering muscle, except for a small (approximately 20%) but significant (P < 0.001) decrease in the white gastrocnemius muscle. Ribose supplementation did not affect subsequent muscle force production after 60 min of recovery. These data indicate that adenine salvage rates were essentially unaltered during recovery from intense contractions.

Adenine↗
PubMed1979

Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart.

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.

Adenine Nucleotides↗
PubMed1968

Suppression of glycine-15N incorporation into urinary uric acid by adenine-8-13C in normal and gouty subjects.

Adenine inhibited the de novo synthesis of purines in both normal and gouty man as shown by inhibition of the incorporation of glycine-(15)N into urinary uric acid without altering the incorporation of glycine-(15)N into urinary creatinine. The diminished purine synthesis did not result in a diminution in the 24 hr excretion of uric acid. This observation was explainable in part by the prompt conversion of adenine to uric acid. In addition to this direct conversion, adenine-8-(13)C provided a slow and prolonged contribution to urinary uric acid.A feedback inhibition of purine synthesis by nucleotides derived from adenine provides the best interpretation of these results.

Adenine Nucleotides↗
PubMed1985

Chronic allopurinol and adenine therapy in Duchenne muscular dystrophy: effects on muscle function, nucleotide degradation, and muscle ATP and ADP content.

Prompted by the controversy on the efficacy of allopurinol in Duchenne muscular dystrophy and by our observations of an abnormal adenine nucleotide turnover in this disease, we conducted an 18 month, double-blind clinical trial with allopurinol and adenine in 14 Duchenne boys paired according to age and functional activity. Detailed clinical evaluation was performed trimonthly. Muscle ATP and ADP content was measured before and after 1 year of treatment. The effect of therapy on adenine nucleotide turnover was determined. No significant difference was observed between the treated and placebo groups, but both showed a significant deterioration (p less than 0.05) in most clinical parameters. Muscle ATP was reduced in Duchenne dystrophy (p less than 0.02) but did not change with therapy, and no correction of the abnormal adenine nucleotide degradation was observed.

Adenine Nucleotides↗
PubMed2000

Correlation between adenine nucleotide-induced cyclic AMP elevation and extracellular adenosine formation in NG108-15 cells.

We previously demonstrated that extracellular adenine nucleotides induced cyclic AMP elevation in NG108-15 cells. This response was resistant to adenosine deaminase (ADA) and the ecto-5'-nucleotidase (CD73) inhibitor alpha,beta-methylene ADP (alpha,beta-MeADP), but was inhibited by both P1- and P2-receptor antagonists. In the present study, we investigated the relationship between adenine nucleotide-induced cyclic AMP elevation and extracellular adenosine formation. ATP, AMP and beta,gamma-methylene ATP (beta,gamma-MeATP) were time-dependently metabolized to adenosine in NG108-15 cells. Adenosine formations from ATP, AMP and beta,gamma-MeATP were not affected by alpha,beta-MeADP, but suppressed by the P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). A close correlation between extracellular adenosine formation and cyclic AMP increasing effects were obtained with several adenine nucleotide agonists in NG108-15 cells as well as their parent cell line C6Bu-1 and N18TG-2 cells, all of which possess functional adenosine A2 receptors. When NG108-15 cells were incubated with [3H]ATP or [3H]AMP in the presence of ADA, [3H]adenosine was found to distribute dominantly on the cell surface. NG108-15 cells expressed mRNA for the ecto-ATPase and nucleotide pyrophosphatase, but not for CD73. These results suggest that local adenosine formation by an ecto-enzyme distinct from CD73 is involved in adenine nucleotide-induced cyclic AMP formation in NG108-15 cells.

Adenine Nucleotides↗
PubMed2001

Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats.

To discover the role of the kidney in tryptophan degradation, especially tryptophan to niacin, rat kidneys were injured by feeding a diet containing a large amount of adenine. The kidney contains very high activity of aminocarboxymuconate-semialdehyde decarboxylase (ACMSD), which leads tryptophan into the glutaric acid pathway and then the TCA cycle, but not to the niacin pathway. On the other hand, kidneys contain significant activity of quinolinate phosphoribosyltransferase (QPRT), which leads tryptophan into the niacin pathway. The ACMSD activity in kidneys were significantly lower in the adenine group than in the control group, while the QPRT activity was almost the same, however, the formations of niacin and its compounds such as N1-methylnicotinamide and its pyridones did not increase, and therefore, the conversion ratio of tryptophan to niacin was lower in the adenine group than in the control group. The contents of NAD and NADP in liver, kidney, and blood were also lower in the adenine group. The decreased levels of niacin and the related compounds were consistent with the changes in the enzyme activities involved in the tryptophan-niacin metabolism in liver. It was concluded from these results that the conversion of tryptophan to niacin is due to only the liver enzymes and that the role of the kidney would be extremely low.

3-Hydroxyanthranilic Acid↗
PubMed1975

Mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. Proton nuclear magnetic resonance studies of the binding of adenine nucleosides and substrate to ethanolamine ammonia-lyase.

Proton NMR spectroscopy was used to study the binding of adenosine, 5'-deoxyadenosine, adenine, and ethanolamine to the adenosylcobalamin-dependent enzyme ethanolamine ammonia-lyase. Broadening of ligand resonances in the presence of ethanolamine ammonia-lyase indicated that adenosine, 5'-deoxyadenosine, and ethanolamine all formed complexes with the enzyme (KD(mM) = 3.5, 3.0, and 2.5 respectively). The methyl group of enzyme-bound 5'-deoxyadenosine rotated at a rate exceeding 10(7) revolutions/s. Adenine did not appear to bind to the enzyme. Rates of dissociation of nucleosides from the enzyme were fast on the NMR time scale, precluding measurements of rate constants for the binding reaction. The departure of ethanolamine was slow, however, permitting their determination. The values for these rate constants were: k1 = 4.4 times 10(5) M-1 S-1; k-1 = 1.1 times 10(3) S-1. Addition of 1 mol of cyanocobalamin/mol of active sites led to narrowing of the enzyme-broadened ligand resonances. With 5'-deoxyadenosine, linewidths still exceeded those of the free ligand, indicating that binding to enzyme was weakened but not abolished. The KD for this nucleoside in the presence of CNCbl was 8.0 mM. With ethanolamine and adenosine, however, linewidths reverted to values characteristic of the unbound ligand, indicating either that CNCbl greatly lowered the rate of dissociation of the ligand or displaced the ligand from the enzyme. A decision between these two possibilities could not be made from the data at hand, although analogy with the situation obtaining with 5'-deoxyadenosine suggests that adenosine is displaced from the enzyme by CNCbl. 5'-Deoxyadenosine inhibited catalytic activity of the enzyme, competing with adenosylcobalamin (Ki = 2.7 mM). Adenosine had no effect, despite NMR evidence indicating that it formed a complex with free enzyme. These experiments showed that ethanolamine ammonia-lyase possesses binding sites for adenine nucleosides, a class of compounds chemically related to the Cobeta-ligand of the cofactor, as well as for ethanolamine. Binding to the enzyme has now been demonstrated for all three categories of low molecular weight compounds thought to be involved in the reaction; namely, substrate (ethanolamine), corrin, and adenine nucleoside.

Adenine↗
PubMed1975

Comparison of tritiated hypoxanthine, adenine and adenosine for purine-salvage incorporation into nucleic acids of the malarial parasite, Plasmodium berghei.

This study was accomplished to examine the relative importance of different metabolic precursors of nucleic acid synthesis in the malarial parasite, P. berghei. Three possible pathways for incorporation of Adenine (type) compounds exist: 1) incorporation via hypoxanthine, 2) via adenine, or 3) via adenosine. The parasitized cell and erythrocyte-free malarial parasite were both examined because of possible metabolic differences that could be encountered. Hypoxanthine was clearly the best precursor at both levels with extra-incorporation in the presence of allopurinol (10(-4)M), which protects oxidative metabolism of hypoxanthine. Adenosine was less efficient in its incorporation into nucleic acids at both levels. Adenine was clearly the poorest precursor being extremely less efficient compared to hypoxanthine 1/50 at parasitized cell level and 1/100 at the free parasite level. At both levels adenine seemed to be slightly more efficient in the presence of allopurinol and this appeared to be a similar to the incorporation via adenosine with allopurinol. In both cases, part of the incorporation could be coming via conversion to hypoxanthine because allopurinol protects oxidation of hypoxanthine via inhibition of xanthine oxidase. With the prior observation of Manandhar and Van Dyke that adenosine is converted to hypoxanthine outside or on the surface of the malarial parasite one is lead to conclude that of the three pathways the hypoxanthine pathway is probably the major and possibly the almost totally important pathway making hypoxanthine's uptake and/or conversion to inosine monophosphate a key event of metabolic and chemotherapeutic importance.

Adenine↗
PubMed1975

Inhibitory effects of adenine nucleotide analogs on the isolated guinea-pig taenia coli.

The inhibitory actions of adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine and 16 adenine nucleotide and nucleoside analogs on the isolated guinea-pig taenia coli preparation were compared with those of adenosine triphosphate (ATP). Responses were quantitated as magnitude of maximal relaxation, time taken to reach maximal relaxation and activity relative to that of ATP. Inhibitory responses induced by the 5'-di- and triphosphates of 2-chloroadenosine and 2-methylthioadenosine resembled those elicited by ADP and ATP, but the 2-substituted analogs were markedly more potent. AMP and adenosine were less active than ATP; their activities were enhanced by 2-chloro substitution but not by 2-methylthio substitution. 2-Methylthio-AMP and 2-methylthioadenosine were the only analogs which did not elicit maximal relaxation of the taenia coli. 6'-Deoxyhomoadenosine 6'-phosphonic acid was inactive. Adenine nucleotide analogs in which the polyphosphate moiety was modified had steeper log dose-response curves than ATP and induced greater maximal responses than ATP. Analogs in which the polyphosphate alpha, beta-anhydride oxygen was replaced by methylene took up to 5 times longer than ATP to cause maximal relaxation. Other analogs with modified or unmodified polyphosphate side chains caused rapid relaxation of the taenia coli. There was no apparent correlation between relative activity and time to reach maximal response. The findings obtained indicate that di- or triphosphate groupings are of prime importance in binding adenine nucleotides to the putative smooth muscle receptor which mediates their inhibitory responses, and that hydrolysis of the terminal phosphates of adenosine 5'-polyphosphates is not a requirement for inhibitory activity. Reasons for the distinctive inhibitory actions of the phosphate-modified adenine nucleotide analogs are considered.

Adenine Nucleotides↗
PubMed1978

Heart phosphofructokinase. Allosteric kinetics following affinity labeling modification of the enzyme by 8-[m-(m-fluorosulfonylbenzamido) benzylthio] adenine.

An adenine analog 8-[m-(m-fluorosulfonylbenzamido)benzylthio]adenine (FSB-adenine) reacts covalently with sheep heart phosphofructokinase. Under conditions optimal for allosteric kinetics the modified enzyme is less sensitive to inhibition by ATP and insensitive to activation by AMP, cyclic AMP, and ADP. The concentration of fructose-6-P necessary for half-maximal activity is markedly decreased, while the cooperativity to the same substrate is not changed under the same conditions. The modified enzyme is more stable at pH 6.5 when compared with the native enzyme. Changes in the allosteric kinetics of the enzyme are proportional to the extent of modification reaching maximal effect when 3.2 mol of the reagent were bound/mol of tetrameric enzyme. Affinity labeling of the enzyme by the adenine derivative does not affect significantly the catalytic site. This is evidenced by the demonstration that under assay conditions optimal for Michaelian kinetics neither the Km for ATP nor for fructose-6-P is significantly changed following chemical modification. Maximal activity of the modified enzyme was 60% of the native enzyme. ADP gives the best protection, while AMP gives less protection against modification by the reagent. ATP slows the rate of the reaction and causes a slight decrease in maximum binding of the reagent to the enzyme. Modification of the enzyme caused a marked reduction of AMP and ADP binding. The evidence indicates that the modified site is a nucleotide mono- and diphosphate activation site.

Adenine↗
PubMed1992

Modulation of anti-Thy1 nephritis in the rat by adenine nucleotides. Evidence for an anti-inflammatory role for nucleotidases.

Extracellular adenine nucleotides are considered mediators of inflammation because they modulate functions of neutrophils and platelets. Until now, this role for adenine nucleotides has not been studied in vivo. In particular in the rat kidney, where ATP- and ADPase activity is present in the glomerular basement membrane, studies about the role of nucleotides may increase our understanding of the dynamics of glomerulonephritis (GN). Therefore, we examined effects of adenine derivatives ATP gamma S, ADP beta S and 2chloro-adenosine (2chloro-ADO) in vitro and during anti-Thy1 GN. The in vitro results show that ADP beta S and ATP gamma S are not degraded by glomerular nucleotidases but, on the other hand do stimulate O2- production of peritoneal exudate cells (PEC). In contrast, 2chloro-ADO significantly inhibits O2- production of peritoneal exudate cells. For in vivo studies rats were rendered nephritic by intravenous injection of monoclonal anti-Thy1 IgG (5 mg/kg body weight). Subsequently, rats were treated with saline (group 1, N = 10), 2chloro-ADO (group 2, N = 10), ADP beta S (group 3, N = 10) or ATP gamma S (group 4, N = 10). All analogs (10 mg/kg body weight) were administered both at t = 0 and t = 12 hour. After 24 hours, rats were sacrificed and kidneys were examined histochemically. In an additional group of nephritic rats (N = 5) proteinuria was studied after 2-chloro-ADO treatment. Results show increased intraglomerular platelet aggregation in nephritic rats treated with ADP beta S, whereas 2chloro-ADO inhibits aggregation significantly as compared with nephritic rats receiving saline. The percentage of granulocytes producing O2- is significantly increased in glomeruli after treatment of nephritic rats with ATP gamma S, whereas cell influx itself is not changed. In contrast, 2chloro-ADO inhibits intraglomerular O2- production, which is associated with the complete inhibition of proteinuria in the early phase of anti-Thy1 GN. These data demonstrate significant pro-inflammatory activities of extracellular adenine nucleotides during anti-Thy1 GN suggesting an anti-inflammatory role for glomerular ATP/ADPase, which in concert with 5' nucleotidase converts ATP and ADP to antiinflammatory ADO.

2-Chloroadenosine↗
PubMedDate not supplied

The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP.

We tested the effect of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) or haloperidol (HP) on the in vitro formation of c-AMP from ATP labelled intracellularly with exogenous 14C-adenine or from endogenous ATP in the slices of rat striatum. DA stimulated the synthesis of c-AMP from endogenous and 14C-adenine labelled ATP. Nonspecific stimulants of the dopaminergic system, APM, AMD and DMAD, stimulated the c-AMP synthesis much weaker than DA did. After application of APM, ADM or DMAD, the utilization of ATP formed from 14C/U/adenine for synthesis of c-AMP was lower than after DA. The effects of combined treatment with DA together with APM, AMD or DMAD was additive. HP, 1 X 10(-3) M did not change the amount of radioactive and total c-AMP, but inhibited the stimulatory action of DA and, to a lesser degree, of APM, AMD and DMAD. The synthesis of c-AMP from endogenous ATP stimulated with APM, AMD and DMAD in striate body slices was inhibited by HP more strongly than the synthesis of c-AMP from ATP labelled with exogenous 14C-adenine. The results indicate that ATP synthesized from intracellular adenyl nucleotides is more effectively utilized for the synthesis of c-AMP stimulated by APM, AMD or DMAD in striate body slices, than ATP labelled with 14C-adenine.

Adenine↗
PubMed1978

5'-adenine mononucleotides in preparations from guinea pig cerebral cortex. Accumulation, translocation and release.

Isolated nerve terminals (synaptosome beds) were prepared from the neocortex of guinea pig and their ability to accumulate and release adenine nucleotides was studied. Synaptosome beds prelabelled with [14C]adenosine released newly synthesized [14C] adenine derivatives on superfusion. Electrical stimulation and K+ depolarization gave augmented output of both [14C] adenine derivatives and lactate from the preparations. Action of metabolic inhibitors on this output was examined. During incubation and superfusion, the synaptosomes displayed glycolysis and synthesis of ATP. Supply of adenine derivatives to the nerve terminals also occurred by translocation from other parts of the tissue.

Adenine Nucleotides↗
PubMed1990

Nerve and drug-induced release of adenine nucleosides and nucleotides from rabbit aorta.

The purpose of the present study was to assess the possible sites which contribute to the nerve stimulation- and alpha-agonist-induced overflow of endogenous adenine nucleosides and nucleotides in vascular tissue. Particular attention was focused on the endothelium because it is known that endothelial cells have a high concentration of ATP and its metabolites. Segments of rabbit thoracic aorta, some denuded of endothelial cells by rubbing the lumen of the vessel, were incubated in organ baths and subjected to transmural nerve stimulation or stimulated with the alpha-1 adrenoceptor agonist methoxamine. A portion of the bathing solution was processed for the determination of norepinephrine by high-performance liquid chromatography with electrochemical detection and a portion for determination of ATP, ADP, AMP and adenosine by high-performance liquid chromatography with fluorescence detection. Transmural stimulation led to a significant release of both norepinephrine and the adenine nucleosides and nucleotides in a ratio of 1 to 350. Removal of the endothelium did not change the release of norepinephrine but reduced the release of adenosine and its derivatives by 90%. Methoxamine also caused the release of adenosine and the adenine nucleotides which was reduced by 93% by removal of the endothelium. Thus, the endothelium seems to be a major source of transmural nerve stimulation and alpha-agonist induced overflow of adenosine and adenine nucleotides. The endothelium is not the exclusive source of these purine congeners, however. In the case of transmural stimulation there is approximately 10% of the total which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1989

[The effect of allopurinol on the synthesis of adenine nucleotides and ribonucleic acid from inosine via a salvage pathway in the brain of rats].

The authors investigated in experiments on rats the action of allopurinol and isoproterenol on the metabolism of adenine nucleotides and the total fraction of ribonucleic acids in the brain, liver heart and kidneys. It was revealed that allopurinol enhances the synthesis of adenine nucleotides from administered inosine in the brain and liver of rats. In the heart and kidneys allopurinol did not affect the synthesis of these compounds. Isoproterenol has a more marked effect on the metabolism of adenine nucleotides in the heart only: it reduced the amount of adenine nucleotides and enhanced their synthesis from inosine. It is assumed that the protective effect of allopurinol on the restoration of the reduced amount of these substances in brain and liver after their ischaemization could take place also by their increased resynthetization from accumulated inosine.

Adenine Nucleotides↗
PubMed1989

Influence of hydrogen peroxide on adenine uptake by iris, ciliary epithelium and corneal endothelium.

Hydrogen peroxide injected into the anterior chamber of adult rabbits causes a sequence of events that is not seen in young normal rabbits, yet is replicated in young rabbits receiving a catalase inhibitor. The uptake of radiolabeled adenine was measured in corneal endothelial, ciliary epithelial, and iris cells of either normal eyes, eyes injected with hydrogen peroxide or inhibitors of glutathione metabolism. Cellular adenine uptake did not exceed that of the bathing solution, except in corneal endothelia and ciliary epithelium of young animals. Under different experimental conditions intracameral hydrogen peroxide decreased adenine uptake into cells of various tissues compared the same experimental condition where only water injections was made. This occurred even with suppression of catalase activity using 3-aminotriazole. Intravitreal glutathione inhibitors had no effect on adenine uptake. The effects of intracameral hydrogen peroxide seen previously might be explained on the basis of alterations in cellular plasma membrane permeability.

Adenine↗
PubMed1989

Decreased erythrocyte phosphoribosylpyrophosphate synthetase activity and impaired formation in thalassemia minor: a mechanism for decreased adenine nucleotide content.

Adenosine triphosphate (ATP) and adenosine diphosphate levels are decreased in erythrocytes from individuals with beta-thalassemia minor. Because 5-phosphoribosyl-1-pyrophosphate (PRPP) is an essential precurosr of adenine nucleotides, we tested the hypothesis that impaired PRPP synthesis is a mechanism for the decreased adenine nucleotide content. Erythrocyte PRPP synthetase activity was significantly decreased, and the Michaelis-Menten constant (Km) for ribose-5-phosphate (R5P) was significantly increased in individuals with alpha-thalassemia minor and those with beta-thalassemia minor. Intact erythrocytes from individuals with alpha-thalassemia and those with beta-thalassemia minor also had an impaired rate of PRPP formation. Both the decrease in PRPP synthetase activity and the impaired PRPP formation were also found in erythrocytes with microcytosis resulting from iron deficiency, indicating that these phenomena may not be specific to thalassemia minor. In all individuals examined, the rate of PRPP formation correlated with ATP content, suggesting that either (1) PRPP synthetase activity is a determinant of ATP content or (2) ATP content is a determinant of PRPP synthetase activity. The depletion of ATP from normal erythrocytes did not affect PRPP synthetase activity, suggesting that ATP content is not a determinant of PRPP synthetase activity. However, a decrease in PRPP synthetase activity did cause an impairment in the rate of adenine nucleotide synthesis, suggesting that PRPP synthetase activity is a determinant of ATP content. Taken together, our results suggest that the decrease in PRPP synthetase activity and the resulting impairment in the rate of PRPP formation are mechanisms for the decreased adenine nucleotide content in thalassemic erythrocytes.

Adenine Nucleotides↗