Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Substrate Cycling”

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 145 records · Page 8Linked to original sources
PubMed1991

Deoxyribonucleotide metabolism in hydroxyurea-resistant V79 hamster cells.

V79 hamster cells were made resistant against hydroxyurea by continuous culture at stepwise increasing drug concentrations. Two cell lines were cloned, resistant to 0.4 mM (V79/H0.4) and 4 mM (V79/H4) hydroxyurea, with a fivefold and a 20-fold increase in soluble ribonucleotide reductase activity. We investigated how the increased amount of enzyme affected the in situ activity of ribonucleotide reductase and deoxyribonucleotide metabolism, in particular substrate cycles between pyrimidine deoxyribonucleosides and their 5'-phosphates. The in situ activity of the reductase was only moderately elevated (1.3-fold in V79/H4 cells). In the fully resistant line, the steady-state level of dATP was increased fourfold, and that of dTTP twofold. These nucleotides are negative allosteric effectors of the reductase and we propose that the increased pools inhibit the enzyme and thereby maintain the in situ activity of the reductase at only a slightly increased level. The surplus deoxyribonucleotides was excreted from the cells as thymidine and deoxycytidine via substrate cycles. The data support and extend our previous model for the regulation of deoxyribonucleotide synthesis via the allosteric properties of ribonucleotide reductase and substrate cycles that link salvage and degradation of deoxyribonucleotides.

Animals↗
PubMed1992

Dynamics of the dATP pool in cultured mammalian cells.

Conditions for labeling the dATP pool of V79 and 3T3 cells from [3H]deoxyadenosine (salvage) or [3H]adenine (via ribonucleotide reduction) were established. With deoxyadenosine the specific radioactivity of dATP reached a constant value after 60 min. In resting 3T3 cells this value was 30 times higher than in S-phase cells. Turnover of dATP and absolute rates of DNA synthesis and excretion of breakdown products of dATP were determined from the accumulation of isotope in various compartments and the specific activity of dATP. In S-phase cells the dATP pool had a half-life of 4 min, identical to that of dTTP determined earlier. Deoxyadenosine was the major breakdown product of dATP in the presence of an inhibitor of adenosine deaminase. The rate of deoxyadenosine excretion of V79 cells amounted to 4% of the rate of dATP incorporation into DNA. Inhibition of DNA replication increased deoxyadenosine excretion 5- to 10-fold, demonstrating a continued de novo synthesis of dATP, albeit at a slightly reduced rate. Our results fit a model involving a substrate cycle between dAMP and deoxyadenosine regulating the dATP pool, similar to the model of substrate cycles involved in the regulation of pyrimidine deoxyribonucleotide pools developed earlier.

3T3 Cells↗
PubMed1998

Microsomal steroid sulfatase: interactions with cytosolic steroid sulfotransferases.

Net sulfation of 4-methylumbelliferone in intact hepatocytes is regulated, in part, by substrate cycling between sulfotransferases (SULT) and arylsulfatases (ARS). Thus, ARS have the potential to influence rates of net sulfate conjugation of a variety of compounds in intact cells via interaction with SULT. Unlike ARSA and ARSB, which are lysosomal, steroid sulfate sulfatase (ARSC, also known as STS) is localized exclusively in the endoplasmic reticulum (ER). The present study was designed to assess the existence and extent of substrate cycling between steroids and their sulfate conjugates through ARSC and SULT, and also to initiate studies of the topology of the catalytic site of ARSC in the rat liver ER. Addition of rat liver microsomes to cytosol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reduced rates of sulfation of dehydroepiandrosterone (DHEA) by SULT, and similarly hydrolysis of DHEA sulfate (DHEAS) was reduced when recombinant human hydroxysteroid SULT was added to rat liver microsomes in the presence of PAPS. There was no evidence for ARSC latency in the presence of detergent at either 4 or 37 degrees C, indicating that facilitated transport of steroid sulfates across the ER membrane may not be required for ARSC activity. The effect of proteases on ARSC activity in intact and disrupted microsomes was determined and compared with effects on components of the glucose-6-phosphatase system known to be localized on the lumenal and cytoplasmic surfaces of the ER. In contrast to the components of the glucose-6-phosphatase system, activity of ARSC in both intact and disrupted microsomes was substantially more resistant to protease inactivation. Our results indicate that substrate cycling of steroids and their sulfates does occur, and suggest that the active site of ARSC may be located within the ER membrane.

Animals↗
PubMed1985

Glycolytic and gluconeogenic states in an enzyme system reconstituted from phosphofructokinase and fructose 1,6-bisphosphatase.

Transitions between glycolytic and gluconeogenic states have been investigated in an open and homogeneous enzyme system containing phosphofructokinase, fructose 1,6-bisphosphatase, pyruvate kinase, adenylate kinase and glucose 6-phosphate isomerase. The direction of substrate flow was found to depend on the maximum activities of phosphofructokinase and fructose 1,6-bisphosphatase as well as on the influx concentrations of fructose 6-phosphate and fructose 1,6-bisphosphate. At high and low maximum activities of phosphofructokinase and fructose 1,6-bisphosphatase unique and stable stationary states occur, whereas at intermediate enzyme concentrations sustained oscillations emerge. Stationary states with a low rate of substrate cycling demand both appropriate enzyme concentrations and an adequate substrate supply. Accordingly, transitions between efficient glycolytic and gluconeogenic states require changes of the enzyme concentrations and of the supply of substrates. Such transitions exhibit a transient oscillatory response. The sustained oscillations generated at intermediate activities of phosphofructokinase and fructose 1,6-bisphosphatase lead to a significant diminution of the rate of substrate cycling when compared with the respective steady state values. During the oscillations glycolytic and gluconeogenic states are consecutively passed through. Because of this a temporal organization of the antagonistic reactions is achieved. In our system the kinetic organization of the two opposite reactions is mainly brought about by the reciprocal allosteric effects of AMP on the activities of the two enzymes.

Adenosine Triphosphate↗
PubMed1985

Influence of fructose 2,6-bisphosphate on the phosphofructokinase/fructose 1,6-bisphosphatase cycle.

In a reconstituted enzyme system multiple stationary states and oscillatory motions of the substrate cycle catalyzed by phosphofructokinase and fructose 1,6-bisphosphatase are significantly influenced by fructose 2,6-bisphosphate. Depending on the initial conditions, fructose 2,6-bisphosphate was found either to generate or to extinguish oscillatory motions between glycolytic and gluconeogenic states. In general, stable glycolytic modes are favored because of the efficient activation of phosphofructokinase by this effector. The complex effect of fructose 2,6-bisphosphate on the rate of substrate cycling correlates with its synergistic cooperation with AMP in the activation of phosphofructokinase and inhibition of fructose 1,6-bisphosphatase.

Fructose-Bisphosphatase↗
PubMed1993

The regulatory, informational, and immunomodulatory roles of fat fuels.

Fat oxidation provides a fuel for many tissues and it provides an important signal to decrease glucose utilization and oxidation in muscle and so conserve glucose for essential organs such as the brain. The control of fatty acid oxidation is achieved in part through its plasma concentrations, which may be precisely controlled by the triacylglycerol-fatty acid substrate cycle, which can also, if oxidation is taken into account, be viewed as a branch point in this important pathway. Branch points may provide precision in regulation if one of the fluxes at the branch is low compared with the other flux. Both branch points and substrate cycles are energetically expensive and may account for some of the increases in energy expenditure in conditions of injury, burns, and sepsis and in the postexercise condition. Fatty acids, through effects on plasma free tryptophan concentrations and hence 5-hydroxytryptamine concentrations in the brain, may play a role in central fatigue. Polyunsaturated fatty acids are claimed to have immunosuppressive properties. Work has been done to provide a biochemical analysis of how they might influence some functions of cells of the immune system.

Amino Acids, Branched-Chain↗
PubMed1976

Metabolic regulations of the rhythmic activity in pacemaker neurons. III. Neutralization of the pentylenetetrazol effect in regularly beating Aplysia neurons by metabolic modifiers.

In regular beating pacemaker neurons isolated from the sea hare Aplysia californica, 30-50 mM pentylenetetrazol (PTZ) induces spike doublets and triplets, multi-spike bursts, and paroxysmal depolarizing shifts. The development of the characteristic PTZ-induced changes in impluse pattern is preceded by a transient increase in discharge frequency and a reduction in after-hyperpolarization. According to earlier findings, the rhythmic spike activity of pacemaker neurons is governed by a phosphofructokinase-fructose-1,6-diphosphatase-mediated substrate cycle, the activation of which leads to the appearance of spike bursts. Inhibitory modifiers of this neuronal substrate cycle, such as citrate, ATP, and 3-phosphoglycerate, are able to neutralize the changes in the impluse characteristics occurring as the result of PTZ action. Since the reinitiated single-spike trains reverted again to the PTZ pattern following the further addition of activating modifiers, such as fructose-1,6-diphosphate or fructose-6-phosphate, it appears likely that PTZ exerts an influence on the metabolic reactions driving the rhythmic spike activity. In contrast to the reversible effects of the metabolic modifiers the conventional anti-convulsants, phenobarbital and pentobarbital, merely block all spike activity.

Adenosine Triphosphate↗
PubMed1987

Hormonal regulation of the rate of the glycogen/glucose-1-phosphate cycle in skeletal muscle.

A method is presented which allows simultaneous estimation of rates of glycogen synthesis and glycogenolysis in an isolated incubated skeletal muscle, thus allowing measurement of the glycogen/glucose-1-phosphate substrate cycling rate. In the absence of hormonal additions, the measured rates of glycogen synthesis and breakdown were similar [respectively, 0.54 +/- 0.12 (8) and 0.74 +/- 0.10 (8) mumol glucosyl equiv. h-1 (g tissue)-1]. Incremental addition of insulin stimulated glycogen synthesis up to threefold and reduced glycogenolysis by about sevenfold; the half-maximally effective concentration of insulin on both processes was about 100 microU/ml (0.7 nM). Incremental addition of adrenaline (in the presence of 1 mU insulin/ml) caused a dramatic increase in the glycogenolytic rate (about 15-fold), but a much less marked inhibition of glycogen synthetic rate. In addition to hormonal manipulation of the muscle preparation in vitro, the effects of cold exposure, the hyperthyroid state, a single exercise bout and exercise-training of animals in vivo on the rates of glycogen synthesis and breakdown in the isolated incubated muscle preparation have been investigated. Significant changes in measured glycogen synthesis, breakdown and glycogen/glucose-1-phosphate cycling have been observed, both under basal conditions and in response to hormonal additions in vitro. The results are discussed with respect to the possible physiological importance of this substrate cycle.

Adaptation, Physiological↗
PubMed1983

Nucleotide triphosphate utilization by cardiac and skeletal muscle sarcoplasmic reticulum. Further evidence for an alternative substrate hydrolysis cycle and the effect of calcium NTPase purification.

It was previously observed that the hydrolysis of GTP by cardiac sarcoplasmic reticulum (SR) (in contrast to skeletal muscle SR: (a) was identical in rate with total ATP hydrolysis; (b) gave a similar nonlinear substrate response; (c) was not Ca2+ dependent; and (d) stimulated Ca2+ accumulation but not Ca2+ translocation. Evidence was presented that both the ATPase and GTPase are effected by the same enzyme and represent different hydrolysis cycles (Van Winkle, W. B., Tate, C. A., Bick, R. J., and Entman, M. L. (1981) J. Biol. Chem. 256, 2268-2274). In the present paper, we report that purification of the NTPase from both muscle sources resulted in an alteration in the NTP concentration response compatible with a single high affinity binding site for ATP only in cardiac SR and for both substrates in skeletal muscle SR. As is the case with native skeletal muscle SR, purified skeletal muscle NTPase hydrolyzed GTP in a manner qualitatively similar to ATP (but with no Ca2+-independent NTPase) but with reduced velocity. In contrast, there was no GTPase activity or Ca2+-independent "basic" ATPase activity in the purified cardiac NTPase. Inclusion of oxalate or the ionophore, A23187, in assays with cardiac SR and ATP as the substrate increased the total ATPase activity but had no effect on GTPase activity. Furthermore, the nucleotide-dependent uptake of oxalate by cardiac SR was only apparent with ATP and not with GTP. In the presence of Ca2+, ATP was a potent inhibitor (noncompetitive, Ki of 2-5 microM) of GTPase activity, whereas it was a weaker competitive inhibitor in the absence of Ca2+. We suggest that GTPase and basic ATPase represent similar alternative enzyme cycles for the CaATPase enzyme that are inhibited by the presence of ATP plus Ca2+ but are rendered inactive during the purification of cardiac NTPase.

Adenosine Triphosphate↗
PubMed2000

Simultaneous in vivo monitoring of hepatic glucose and glucose-6-phosphate by (13)C-NMR spectroscopy.

Hepatic glucose-6-phosphate (G6P) was monitored non-invasively in rat liver by in vivo (13)C NMR spectroscopy after infusion of [1-(13)C] glucose. The phosphorylation of glucose to G6P yields small but characteristic displacements for all of its (13)C-NMR resonances relative to those of glucose. It is demonstrated that in vivo (13)C-NMR spectroscopy at 7 Tesla provides the spectral sensitivity and resolution to detect hepatic G6P present at sub-millimolar concentration as partially resolved low-field shoulders of the glucose C1 resonances at 96.86 ppm (C1beta) and 93. 02 ppm (C1alpha). Upon (13)C-labeling, the intracellular conversion of [1-(13)C] glucose to [1-(13)C] G6P could be monitored, which allowed the hepatic glucose-G6P substrate cycle to be assessed in situ. The close correlation found for the (13)C labeling patterns of glucose and G6P supports the concept of an active substrate cycle whose rate exceeds that of net hepatic glucose metabolism. High-resolution (13)C-NMR spectroscopy and biochemical analyses of tissue biopsies collected at the end of the experiments confirmed qualitatively the findings obtained in vivo.

Animals↗
PubMed1985

Quantitative histochemical assessment of regional differences in hepatic glucose uptake and release.

As a further step in the investigation of the heterogeneity of liver cells in general and regionality of glucose metabolism in particular, requirements for isolation of appropriate tissue samples were defined and procedures for measurement of the biochemical parameters responsible for glucose uptake and release developed and tested. By using enzymatic cycling for chemical amplification, in conjunction with the oil-well technique, sufficient analytical sensitivity was provided to assay samples averaging 20 ng dry weight. Microchemical data on the distribution of glucokinase and glucose-6-phosphatase and of their substrates, glucose and glucose-6-P, were used to, first calculate in vivo rates of these catalytic steps by means of the Michaelis-Menten equation, and then, to determine the direction and rate of net glucose flux, as well as, the rate of substrate cycling between glucose and glucose-6-P. Calculations from the results indicated a reciprocal distribution of in vivo glucokinase and glucose-6-phosphatase velocities, as well as, sex-specific differences. The distribution of in vivo activities results in a spatial separation of these antagonistic steps. Separation is incomplete, but nevertheless appears to lead to regionally different rates in futile substrate cycling. Glucose gradients permit differentiation between net glucose uptake and release and were, therefore, used as a test of the validity of the calculations of in vivo activities. The observed discrepancies between glucose gradients and calculated in vivo enzyme activities illustrate the power of this approach: it provides a way to compare changes in glucose along the sinusoid with what would be predicted from the levels of enzymes which liberate and tie up glucose and of their respective substrates.

Animals↗
PubMed2005

A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome.

An impressive body of epidemiological evidence suggests that a history of large perturbations in body weight earlier in life, independently of excess weight, is a risk factor for later development of insulin-related complications, namely central obesity, type 2 diabetes and cardiovascular disease. Such an increased risk has been reported in men and women who in young adulthood experienced weight fluctuations that involved weight recovery after weight loss caused by disease, famine or voluntary 'yoyo' dieting, and is particularly strong when the weight fluctuations occurred much earlier in life and are characterized by catch-up growth after foetal and/or neonatal growth retardation. As the phase of weight recovery/catch-up growth is associated with both hyperinsulinaemia and an accelerated rate for recovering fat mass (i.e. catch-up fat), the questions arise as to whether, why and how processes that regulate catch-up fat might predispose to hyperinsulinaemia and to insulin-related diseases. In addressing these issues, this paper first reviews evidence for the existence of an adipose-specific control of thermogenesis, whose suppression contributes to the phenomenon of catch-up fat during weight recovery/catch-up growth. It subsequently concentrates upon recent findings suggesting that: (i) such suppression of thermogenesis directed at catch-up fat is accompanied by a redistribution of glucose from skeletal muscle to white adipose tissue, and (ii) substrate cycling between de novo lipogenesis and lipid oxidation can operate as a thermogenic effector in skeletal muscle in response to signalling interactions between leptin and insulin - two key 'adiposity' hormones implicated in the peripheral control of substrate metabolism. These new findings are integrated into the proposal that, in its 'evolutionary adaptive' role to spare glucose for rapid rebuilding of the fat stores, suppressed thermogenesis in skeletal muscle - via inhibition of substrate cycling between de novo lipogenesis and lipid oxidation - confers to the phase of weight recovery/catch-up growth its high sensitivity towards the development of insulin resistance and hyperinsulinaemia, and hence towards diseases that are clustered around the insulin resistance syndrome.

Adipose Tissue↗
PubMed1985

Metabolic control and its analysis. Additional relationships between elasticities and control coefficients.

Existing theorems from the analysis of metabolic control have been taken and embedded in a simple matrix algebra procedure for calculating the flux control coefficients of enzymes (formerly known as sensitivities) in a metabolic pathway from their kinetic properties (their elasticities). New theorems governing the flux control coefficients of branched pathways and substrate cycles have been derived to allow the procedure to be applied to complex pathway configurations. Modifications to the elasticity terms used in the equations have been theoretically justified so that the method remains valid for pathways with conserved metabolites (for example, the adenine nucleotide pool or the intermediates of a catalytic cycle such as the tricarboxylic acid cycle) or with pools of metabolites kept very near to equilibrium by very rapid reactions. The matrix equations generated using these theorems and relationships may be solved algebraically or numerically. Algebraic solutions have been used to determine the factors responsible for the degree of amplification of flux control coefficients by substrate cycles and to show that it is possible to derive expressions for the elasticities of a group of enzymes.

Biological Transport↗
PubMed1983

Metabolism of [U-14C, 2-3H] glucose in rat liver during non-recirculating perfusion: effects of insulin.

Livers from fed male rats were perfused in a non-recirculating manner with undiluted blood containing either 6 or 13 mM [U-14C,2-3H] glucose. At the lower concentration there was a small output of glucose which was unaffected by insulin whereas at the high concentration there was a substantial uptake of glucose which was significantly increased by the hormone. The rate of metabolism of [2-3H] glucose was greater than that of [U-14C] glucose in all experiments indicating an active substrate cycle between glucose:glucose 6-phosphate. Cycling was unaffected by insulin at the lower glucose concentration but was increased by perfusion with 13 mM glucose, the latter increase being abolished by insulin. These data show that although the perfused liver acts to autoregulate blood glucose, this is not achieved solely at the substrate cycle glucose:glucose 6-phosphate.

Animals↗
PubMed1997

Decreased white fat cell thermogenesis in obese individuals.

OBJECTIVE: To investigate whether white adipocyte thermogenesis and energy metabolism are reduced in obese individuals. SUBJECTS: Eight lean and 15 obese men and women; BMI 19-41. DESIGN: Isolated subcutaneous adipocytes were maintained in agarose gel for 20h under basal conditions and subsequently for 10h after stimulation with 1 microM isoprenaline. Direct microcalorimetry was performed continuously over 30h while biochemical measures were obtained after 0, 20, 25 and 30h. MEASUREMENTS: Total cellular thermogenesis, oxygen consumption, glycolysis, lipolysis, triglyceride/FFA substrate cycle, adenine nucleotides, DNA content as basis of reference. RESULTS: Under basal and stimulated conditions, thermogenesis (5.6 and 8.6 microW/microgDNA, respectively; P < 0.0001) correlated negatively (P < 0.01 and P < 0.05, respectively) with the BMI and positively with O2 and glucose consumption, lactate, glycerol, FFA release and FFA re-esterification. Reduced basal lactate production with increased BMI (P < 0.05) indicates a more aerobic adipocyte metabolism in obese individuals. Negative correlation between BMI and stimulated triglyceride/FFA substrate cycle activity (P < 0.01) explains the decreased hormone induced adipocyte heat production in the obese. CONCLUSIONS: The results suggest that a reduction of total body energy expenditure, which is discussed to cause obesity, can be associated with distinct metabolic alterations at a cellular level. However, since the estimated total body fat cell thermogenesis does not exceed 7% of the resting metabolic rate, the observed decrease of adipocyte heat production in the face of augmented BMI can only in part be responsible for the development of obesity.

Adipocytes↗
PubMed2001

[Intermittent hypoxic training with exogenous nitric oxide improves rat liver mitochondrial oxidation and phosphorylation during acute hypoxia].

It have been shown that NO plays primary role in several mitochondrial functions. Our objective for this study was to investigate whether exogenous NO (L-arginine) modulates the adaptive reactions of rat liver tissue respiration and lipid peroxidation on intermittent hypoxic training (IHT). In control animals the test with acute hypoxia (7% O2, 30 min) provoked sharp augmentation of ADP-stimulating tissue respiration with the increase of respiratory coefficient and phosphorylation rate, the decrease of O2 uptake efficacy and switching the energy supply to succinate oxidation pathway with the inhibition of aminotranspherase Krebs cycle substrates supply mechanism. The twice augmentation of malon dialdehyde content (MDA) was observed. The same hypoxic test but after 14 days of IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily) produced a stimulation of oxidative phosphorylation with primary activation of aminotranspherase pathway, the marked increase of ADP/O ratio on the background of a decrease of MDA content by 32%. The combination of IHT with L-arginine treatment (600 Mg/Kg intraperitoneally, daily before IHT sessions) provoked a decrease of tissue oxygen consumption, the inhibition of both aminotranspherase and succinateoxidase Krebs cycle substrates supply mechanism on the background of pronounced MDA decrease (by 120%) in comparison with untrained animals. L-arginine effects abolished by the NO-synthase blocker L-NNA. We conclude that the combination of IHT which promotes the increase of inner adaptive mechanisms with NO-donors treatment could significantly increase the tolerance to episodes of acute hypoxia.

Adaptation, Physiological↗
PubMed1977

Regional cerebral energy metabolism in acute carbon monoxide intoxication.

The regional cerebral metabolic effects of 30 min of exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) were studied in lightly anesthetized rats by measurement of energy phosphates and glycolytic - citric acid cycle substrates in the basal ganglia, hippocampus-thalamus, and cerebellum. In all three regions 0.5 and 1.0% CO gave rise to increases in tissue lactate, but since ATP and the energy charge of the adenylate pool (ECP) remained unchanged from control, it is concluded that energy state was unaltered at these levels of CO. At 1.5% CO the basal ganglia region showed decreases in ATP and ECP, whereas these values for cerebellum and hippocampus=thalamus were unchanged from control. At 2.0% CO all areas showed decreases in APT and ECP and increases in ADP and AMP. The patterns of change in glycolytic and citric acid cycle substrates were similar in all three areas. The results indicated that the energy homeostasis of the basal ganglia is less well maintained in this form of experimental hypoxia.

Adenosine Diphosphate↗
PubMed1990

Effects of cytosine arabinoside and hydroxyurea on the synthesis of deoxyribonucleotides and DNA replication in L1210 cells.

Experiments were carried out in L1210 cells to examine the importance of 'substrate cycles' in regulating the intracellular levels of deoxyribonucleoside 5'-triphosphate. L1210 cells were incubated with [14C]cytidine or [14C]adenosine in the presence and absence of hydroxyurea or cytosine arabinoside (araC). These incubations were carried out for either 30 or 120 min. Inhibition of ribonucleotide reductase by hydroxyurea resulted in the blockage of the flux of ribonucleotides to deoxyribonucleotides (greater than 90%) as expected. When DNA synthesis was inhibited with araC, there was a marked decrease in the incorporation of [14C]cytidine or [14C]adenosine into DNA as deoxyribonucleotides. However, there was not a corresponding increase in the deoxyribonucleotide levels in the acid-soluble fraction or deoxyribonucleosides in the culture medium. AraC treatment decreased the total formation of deoxyribonucleotides. These data indicate that L1210 cells do not regulate the intracellular pools of dNTPs via 'substrate cycles' which involve activation of phosphatases when DNA synthesis is blocked or activation of kinases when ribonucleotide reductase is inhibited.

Adenosine↗