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PubMed1992

Effect of prior exercise and insulin on potential thermogenic systems in rat skeletal muscle.

We previously reported that insulin stimulates oxygen consumption by the perfused rat hindquarter after high-intensity exercise. The purpose of the present study was to examine whether fructose 6-phosphate-fructose 1,6-bisphosphate cycling or an uncoupling of mitochondrial respiration contributes to this phenomenon. Hindquarter skeletal muscle was analyzed after perfusion in the absence or presence of insulin (150-200 microU/ml) for high-energy phosphate content, fructose 6-phosphate-fructose 1,6-bisphosphate cycling of glucose before incorporation into glycogen, and mitochondrial respiratory control. Muscle from exercised rats perfused with insulin did not display greater rates of glucose cycling or mitochondrial uncoupling; in fact, insulin decreased the rate of fructose 6-phosphate cycling and tended to increase respiratory control in skeletal muscle mitochondria. In addition, the concentrations of ATP and creatine phosphate and the calculated free ADP level in muscle of previously exercised rats perfused with insulin were similar to those of control rats. The results do not exclude the possibility that localized subcellular changes in ADP occurred, however. In conclusion, the results suggest that insulin-induced increases in other substrate cycles, ion transport systems, and/or as yet unidentified energy-requiring processes account for the 25-30% increase in hindquarter oxygen consumption after intense exercise.

Animals↗
PubMed1990

Energy cost of absorption and metabolism in the ruminant gastrointestinal tract and liver: a review.

Contributions of various biochemical processes to overall energy expenditure in the gastrointestinal tract (GIT) and liver have been assessed in this review. The GIT and liver are responsible for a disproportionately high fraction of whole-body energy utilization. The energetic cost of Na+, K(+)-ATPase, protein synthesis and degradation, substrate cycling and urea synthesis contribute substantially to energy expenditure in the ruminant. In the splanchnic bed, these biochemical processes account for approximately 22.8% of whole-body O2 and, consequently, ATP utilization; they are influenced by several factors, including dietary composition, level of intake, age, endocrine status and physiological state. In the GIT and liver, the energetic cost of Na+, K(+)-ATPase is by far the most energetically demanding process; it is related to the active transport of substrates and the maintenance of ionic homeostasis. The high rate of protein synthesis in the GIT is associated with cellular turnover and sloughing, secretion and enzymatic action. In the liver, protein synthesis is important in the mediation of hormonal induction, which influences regulation of body systems, synthesis of plasma proteins, enzymatic and cellular turnover and detoxification of blood. Regulation of these processes and the signals involved in the differential contribution of each biochemical event are not well understood. The large contribution of these biochemical events in the GIT and liver to whole-animal energy utilization suggests that their manipulation may alter the energetic efficiency of meat, milk or wool production.

Absorption↗
PubMed1993

Measurement of anaerobic capacities in humans. Definitions, limitations and unsolved problems.

Anaerobic capacity is defined as the maximal amount of adenosine triphosphate resynthesized via anaerobic metabolism (by the whole organism) during a specific mode of short-duration maximal exercise. This review focuses on laboratory measures which attempt to quantify anaerobic capacity; it examines the evidence supporting or challenging the validity of these measures and provides research foci for future investigations. Discussion focuses on anaerobic capacity measured during running and cycling, since almost all data reviewed were collected using these exercise modes. The validity of the oxygen debts (alactic and total), maximal blood lactate and oxygen deficit as measures of anaerobic capacity was examined. The total oxygen debt, now termed the excess post-exercise consumption, was used in investigations in the 1920s and 1930s to quantify anaerobic energy production; it has since been shown to be an invalid measure of anaerobic capacity, since its magnitude is known to be influenced by factors (e.g. temperature, catecholamines, substrate cycling, lactate glycogenesis) other than those directly involved in anaerobic metabolism. Maximal blood lactate, a measure also used in some of those early investigations, is often used in exercise and sports physiology. Opinion on the utility of maximal blood lactate as an estimate of anaerobic (lactic) capacity is, however, divided. Despite problems interpreting the physiological meaning of maximal blood lactate levels (due primarily to acute changes in blood volume), this measure is still used in both research and athletic settings to describe anaerobic capacity. Its use is supported by (a) the high correlations observed between maximal blood lactate and short-duration exercise performance presumably dependent upon anaerobic capacity, and (b) the higher maximal blood lactate values observed in sprint and power athletes (who would demonstrate higher anaerobic capacities) compared with endurance athletes or untrained people. However, training-induced changes in other performance, physiological and biochemical markers of anaerobic capacity have not always been paralleled by changes in maximal blood lactate; its relatively high variability also diminishes its usefulness to athletic populations, since relatively small changes in anaerobic capacity may not be detected by a measure with such high variability. These latter findings may be partially related to the confounding influence of blood volume which often changes in response to short and long term exercise demands. Maximal blood lactate is known to be influenced by the intensity and duration of the preceding exercise bout; therefore, it is plausible that these factors may also influence the degree to which maximal blood lactate accurately reflects anaerobic capacity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

[Tissue respiratory enzymes in the rat liver in acute blood loss].

An increase in activity of several dehydrogenases of tricarboxylic acid cycle (NADP-dependent malate dehydrogenase, alpha-ketoglutarate dehydrogenase) was observed in rat liver tissue under conditions of acute hemorrhage. The enzymatic activity was slightly higher in the group of animals with relatively prolonged life-time as compared with those, which lived less than 4 hrs. Activity of cytochrome oxidase was inhilited in the both groups of animals (by 27% and 29%, respectively). The less distinct decrease in both temperature in the group of animals with prolonged life-time might maintain the rate of Krebs cycle substrates oxidation. Activation of respiration in liver tissue under conditions of the hemorrhage is considered as a compensatory reaction tending to improve oxygen utilization in hypoxia. At the same time, inhibition oy cytochrome oxidase demonstrates the impairment of electron transport and decreased rate of energy production in liver mitochondria.

Acute Disease↗
PubMedDate not supplied

[Krebs cycle in tissue of rats subjected to combined effect of hypercapnia, hypoxia and cooling].

The content of the Krebs cycle substrates and activity of dehydrogenases corresponding to them were studied in the brain and myocardium tissues of the non-linear male rats adapted to acute hypoxia under conditions of the altered gas medium. The content of malate and succinic acid was studied in the liver and skeletal muscles only. In the brain the total activity of malate dehydrogenase (MDH, EC 1.1.1.37, 1.1.1.39) alpha-ketoglutarate dehydrogenase (KDH, EC 1.2.4.2) pyruvate dehydrogenase (PDH, EC 1.2.4.1) and isocitrate dehydrogenase (ICDH, EC 1.1.1.41-42) is shown to be decreased and kept to be lowered in all the periods of the study. No essential shifts in the activity of these dehydrogenases were found in the myocardium. The activity of succinate dehydrogenase (SDH, EC 1.3.99.1) in both tissues lowers 48 h after the effect of the mentioned factors. Simultaneously the greatest changes in the level of the substrates were observed in the myocardium, in the brain they were less developed. In the liver the content of malate increases without pronounced changes in the amount of succinic acid and in the skeletal muscles the level of malate and succinic acid lowers.

Acclimatization↗
PubMed1975

Effect of tryptophan and its metabolites on gluconeogenesis in mammalian tissues.

In parenchymal cells from starved mice L-tryptophan is a potent inhibitor of gluconeogenesis from substrates giving rise to oxaloacetate. Quinolinate yields a different pattern of inhibition and is generally much less effective. Tryptamine, indole 3-acetaldehyde and indole 3-acetate are equally as effective as tryptophan. Tryptamine inhibition alone may be overcome by pargyline; serotonin does not prevent the inhibition due to tryptophan. In kidney slices from starved rats, however, tryptophan has no effect on gluconeogenesis. Indole 3-acetate is also relatively ineffective, but quinolinate is signficiantly more potent than in liver; at 0.1mM, glucose production from lactate is 50% inhibited. Quinolinate is less effective with citric acid cycle substrates; the pattern of inhibition is consistent with a direct action on phosphoenolpyruvate carboxykinase. There is no evidence that glutamate dehydrogenase is simultaneously inhibited.

Animals↗
PubMed1988

Inhibition of mitochondrial respiration by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse brain in vivo.

This is the first report on in vivo effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration in mouse brain. C57/BL mice, injected with 40 mg/kg of MPTP subcutaneously, were sacrificed by cervical dislocation 5-6 h after the injection. Mitochondrial suspensions were prepared from whole brains. Mitochondrial respiration was studied polarographically. The state 3 respiration, i.e., the active respiration in the presence of tricarboxylic acid (TCA) cycle substrates and ADP with coupled phosphorylation of ADP to ATP, was significantly inhibited in mice treated with MPTP. This inhibition was prevented by pretreatment of mice with pargyline. Activity of mitochondrial NADH-ubiquinone oxidoreductase was also inhibited in mice treated with MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1977

Biochemical background of atherosclerotic heart lesion in an experiment.

The authors investigated enzymic systems and corresponding substrate cycles that transport hydrogen across the mitochondrial membrane in a myocardium with experimental cholesterol-induced atherosclerosis. Sensitive spectrophotometric methods were used for assessing the activities of cytoplasmic and mitochondrial enzymes: lactate and alpha-glycerphosphate dehydrogenases, and of characteristic mitochondrial enzymes: glutamate and beta-hydroxybutyrate dehydrogenases. Specific enzymological methods were used in determining the concentrations of lactic, pyruvic, glycerophosphoric, dihydroacetonephosphoric, malic, oxaloacetic, glutamic, alpha-ketoglutaric, acetoacetic, and beta-hydroxybutyric acids. The cytoplasmic NAD/NADH quotient was calculated. The investigators found a reduction of enzymic activities in the "shuttle" transport system studied, marked deviations from normal levels of their substrates, and a reduction of the NAD/NADH quotient by the factor 0.56. All these phenomena represent a biochemical background of a complex of symptoms characterizing severe myocardial lesion in experimental atherosclerosis.

Animals↗
PubMed1985

Dynamic structures of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle in a reconstituted enzyme system.

The dynamics of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle was investigated in an open and homogeneous system reconstituted from purified enzymes. In addition to phosphofructokinase and fructose 1,6-bisphosphatase, pyruvate kinase, adenylate kinase and glucose 6-phosphate isomerases are involved. The time evolution of the metabolite concentrations is governed by a set of differential equations which take into account flow processes and enzymic conversions of metabolites. Depending on the experimental parameters stable attractors, multiple states and sustained oscillations occur. The main source of the nonlinear dynamics is the reciprocal effect of AMP on the activities of phosphofructokinase and fructose 1,6-bisphosphatase. States are characterized by the net flow rates of substrates and by the rate of futile substrate cycling. For efficient glycolytic states high ratios between the influx rates of fructose 6-phosphate and fructose 1,6-bisphosphate and between the maximum activities of phosphofructokinase and fructose 1,6-bisphosphatase must be maintained, while for an efficient gluconeogenic mode the reverse must hold. Fructose 2,6-bisphosphate exerts reciprocal effects on the activities of phosphofructokinase and fructose 1,6-bisphosphatase. In dependence on the experimental conditions fructose 2,6-bisphosphate was found either to generate or to extinguish oscillations.

Animals↗
PubMed1990

Regulation of 5-phosphoribosyl 1-pyrophosphate and of hypoxanthine uptake and release in human erythrocytes by oxypurine cycling.

Uptake and release of purines by red blood cells has been shown to be markedly sensitive to changes in pH, inorganic phosphate (Pi), and oxygen concentration (Berman, P., Black, D., Human, L., and Harley, E. (1988) J. Clin. Invest. 82, 980-986). The mechanism of this regulation has been further studied. We have shown that incubation of red cells in medium containing xanthine oxidase rapidly and completely depletes intracellular hypoxanthine and causes accumulation of 5-phosphoribosyl 1-pyrophosphate (PRPP) at physiological Pi concentrations. Hypoxanthine release from intracellular IMP is strictly dependent on PRPP depletion, induced by either alkalinizing the cells or by adding excess adenine. Xanthine oxidase abolishes this dependence. Oxygen depletion enhances adenine uptake and prevents hypoxanthine release. The results suggest that hypoxanthine release is governed by PRPP-dependent recycling of hypoxanthine to IMP. We propose that PRPP accumulation in red cells is regulated by a substrate cycle, comprising hypoxanthine, IMP, and inosine. Cycle flux is controlled by Pi inhibition and 2,3-bisphosphoglycerate activation of purine-5'-nucleotidase, which converts IMP to inosine. Oxypurine cycling may account for the sensitive control of purine uptake and release by changes in pH and oxygen tension that occur physiologically.

Biological Transport↗
PubMed1983

Metabolic control of hepatic gluconeogenesis during exercise.

Prolonged exercise increased the concentrations of the hexose phosphates and phosphoenolpyruvate and depressed those of fructose 1,6-bisphosphate, triose phosphates and pyruvate in the liver of the rat. Since exercise increases gluconeogenic flux, these changes in metabolite concentrations suggest that metabolic control is exerted, at least, at the fructose 6-phosphate/fructose 1,6-bisphosphate and phosphoenolpyruvate/pyruvate substrate cycles. Exercise increased the maximal activities of glucose 6-phosphatase, fructose 1,6-bisphosphatase, pyruvate kinase and pyruvate carboxylase in the liver, but there were no changes in those of glucokinase, 6-phosphofructokinase and phosphoenolpyruvate carboxykinase. Exercise changed the concentrations of several allosteric effectors of the glycolytic or gluconeogenic enzymes in liver; the concentrations of acetyl-CoA, ADP and AMP were increased, whereas those of ATP, fructose 1,6-bisphosphate and fructose 2,6-bisphosphate were decreased. The effect of exercise on the phosphorylation-dephosphorylation state of pyruvate kinase was investigated by measuring the activities under conditions of saturating and subsaturating concentrations of substrate. The submaximal activity of pyruvate kinase (0.5 mM-phosphoenolpyruvate), expressed as percentage of Vmax., decreased in the exercised animals to less than half that found in the controls. These changes suggest that hepatic pyruvate kinase is less active during exercise, possibly owing to phosphorylation of the enzyme, and this may play a role in increasing the rate of gluconeogenesis.

Animals↗
PubMed2006

Cloning of multiple cellulase cDNAs from Volvariella volvacea and their differential expression during substrate colonization and fruiting.

We used PCR-based methods to clone and sequence four previously unidentified cellulase cDNAs: cbhI-I, cbhI-II, cbhII-I and egII. CbhI-I, cbhI-II and cbhII-I consist of 1710, 1610 and 1453 bp, respectively, and encode for 512, 458 and 442 amino acids, respectively. EgII consists of 1180 bp encoding for 310 amino acids, and belongs to family 61 of the glycosyl hydrolases. CbhI-I, cbhII-I and egII all have a modular structure, with the catalytic domain (CD) and cellulose-binding domain (CBD) located at the C-terminus in cbhI-I and egII, and at the N-terminus in cbhII-I. CbhI-II shows high homology to cbhI-I but lacks a CBD. Northern blotting revealed that cbhI-I, cbhI-II and cbhII-I were coordinately expressed at various stages of the mushroom developmental cycle (substrate colonization to mature fruit body), although the number of cbhI-I transcripts was much smaller. No egII expression was detectable during the substrate colonization phase but transcription levels increased as fruit body morphogenesis progressed.

Amino Acid Sequence↗
PubMed2000

ATP-dependent substrate occlusion by the human erythrocyte sugar transporter.

Human erythrocyte sugar transport presents a functional complexity that is not explained by existing models for carrier-mediated transport. It has been suggested that net sugar uptake is the sum of three serial processes: sugar translocation, sugar interaction with an intracellular binding complex, and the release from this complex into bulk cytosol. The present study was carried out to identify the erythrocyte sugar binding complex, to determine whether sugar binding occurs inside or outside the cell, and to determine whether this binding complex is affected by cytosolic ATP or transporter quaternary structure. Sugar binding assays using cells and membrane protein fractions indicate that sugar binding to erythrocytes is quantitatively accounted for by sugar binding to the hexose transport protein, GluT1. Kinetic analysis of net sugar fluxes indicates that GluT1 sugar binding sites are cytoplasmic. Intracellular ATP increases GluT1 sugar binding capacity from 1 to 2 mol of 3-O-methylglucose/mol GluT1 and inhibits the release of bound sugar into cytosol. Reductant-mediated, tetrameric GluT1 dissociation into dimeric GluT1 is associated with the loss of ATP and 3-O-methylglucose binding. We propose that sugar uptake involves GluT1-mediated, extracellular sugar translocation into an ATP-dependent cage formed by GluT1 cytoplasmic domains. Caged or occluded sugar has three possible fates: (1) transport out of the cell (substrate cycling); (2) interaction with sugar binding sites within the cage, or (3) release into bulk cytosol. We show how this hypothesis can account for the complexity of erythrocyte sugar transport and its regulation by cytoplasmic ATP.

3-O-Methylglucose↗
PubMed1981

The antiketogenic effect of alanine in normal man: evidence for an alanine-ketone body cycle.

The effect of alanine on ketone body levels, independent of hormonal changes, in normal man has been investigated. Five normal subjects were given somatostatin infusions (200 micrograms/hour) for 3 hr. After 1 hr alanine or isotonic saline was infused for 2 hr. With saline blood beta-hydroxybutyrate and acetoacetate levels rose steadily to a peak of 0.230 plus or minus 0.053 and 0.112 plus or minus 0.023 mmole/l respectively. With alanine beta-hydroxybutyrate and acetoacetate levels plateaued at 0.099 plus or minus 0.020 and 0.055 plus or minus 0.006 mmole/l respectively. Alanine levels reached nearly 1 mmole/l but a significant effect on ketone body levels was apparent at physiologic levels (less than 0.6 mmole/l). Plasma fatty acid and glycerol levels did not change significantly. Insulin C-peptide and glucagon levels were suppressed to a similar extent in both experiments. These results support the view that alanine suppresses ketogenesis in man by a direct hepatic effect independent of insulin and glucagon. It is suggested that this forms part of a negative feedback substrate cycle between alanine and ketone bodies.

3-Hydroxybutyric Acid↗
PubMed1979

The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes.

1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of O(2) uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of O(2) uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of O(2) uptake to heat output from 1.94+/-0.05 in the controls to 1.52+/-0.04 and 1.54+/-0.01mumol/J respectively. 5. Glucagon (1mum), which slightly increased both O(2) uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NH(4)Cl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of O(2) uptake to heat output from 1.81+/-0.08 to 1.47+/-0.06mumol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of O(2) uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell O(2) uptake to heat output between homozygote Zucker fa/fa obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of O(2) uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling.

Animals↗
PubMed2004

Flavoenzyme-catalyzed redox cycling of hydroxylamino- and amino metabolites of 2,4,6-trinitrotoluene: implications for their cytotoxicity.

The toxicity of 2,4,6-trinitrotoluene (TNT), a widespread environmental contaminant, is exerted through its enzymatic redox cycling and/or covalent binding of its reduction products to proteins and DNA. In this study, we examined the possibility of another cytotoxicity mechanism of the amino- and hydroxylamino metabolites of TNT, their flavoenzyme-catalyzed redox cycling. The above compounds acted as redox-cycling substrates for single-electron transferring NADPH:cytochrome P-450 reductase (P-450R) and ferredoxin:NADP(+) reductase (FNR), as well as substrates for the two-electron transferring flavoenzymes rat liver NAD(P)H:quinone oxidoreductase (NQO1) and Enterobacter cloacae NAD(P)H:nitroreductase (NR). Their reactivity in P-450R-, FNR-, and NR-catalyzed reactions increased with an increase in their single-electron reduction potential (E(1)(7)) or the decrease in the enthalpy of free radical formation. The cytotoxicity of the amino- and hydroxylamino metabolites of TNT towards bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was partly prevented by the antioxidant N,N'-diphenyl-p-phenylene diamine and desferrioxamine, and potentiated by 1,3-bis-(2-chloroethyl)-1-nitrosourea, thus pointing to the involvement of oxidative stress. In general, their cytotoxicity increased with an increase in their electron accepting properties, or their reactivity towards the single-electron transferring FNR and P-450R. Thus, our data imply that the flavoenzyme-catalyzed redox cycling of amino and hydroxylamino metabolites of TNT may be an important factor in their cytotoxicity.

Amines↗
PubMed1991

Effect of exercise on recovery changes in plasma levels of FFA, glycerol, glucose and catecholamines.

The prolonged effects of acute exercise on the plasma concentrations of FFA, glycerol, glucose and catecholamines were examined. Twelve young men performed exhaustive prolonged exercise on a cycle ergometer (80 minutes at 70-75% of VO2 max), and in separate experiments they exercised for shorter durations (20, 40 and 80 minutes) and at lesser intensities (29, 50 and 75% of VO2 max). Carbohydrate-rich meals were given 2, 7 and 12 hours after exercise. Blood samples were taken while the subjects rested in bed during a 12-14-hour recovery period. Control experiments without exercise were also performed. In some subjects the plasma concentration of FFA after exhaustive exercise was increased to levels considered to be potentially hazardous, and the mean plasma level of FFA was increased for 6 hours and that of glycerol was increased for 2.5 hours after exercise. The plasma concentration of glucose was generally reduced for 12 hours after exhaustive exercise. Plasma catecholamines were increased for 2 hours after exhaustive exercise. We observed a preprandial increase in FFA and glycerol concentrations during recovery from exercise which was related to the duration and intensity of exercise. These findings indicate that the rates of FA utilization and TG-FA substrate cycling were increased in the recovery period after exercise, and that the magnitude of both depends on the duration and intensity of exercise.

Adult↗
PubMed1985

Temporal organization of the phosphofructokinase/fructose-1,6-biphosphatase cycle.

The dynamic and functional organization of the fructose-6-phosphate/fructose-1,6-bisphosphate cycle has been investigated in an open and homogeneous reconstituted enzyme system containing phosphofructokinase, fructose-1,6-biphosphatase, pyruvate kinase, adenylate kinase and glucose 6-phosphate isomerase. The properties of this system were analyzed by a model based on the kinetic properties of the individual enzymes. It could be shown that in a broad parameter region sustained oscillations arise. At low maximum activities of phosphofructokinase a domain of multiple stationary states occurs, in which stable stationary states can coexist with a stable oscillatory or with an alternate stable stationary state. The occurrence of oscillations and the emergence of alternate stationary motions are caused mainly by the reciprocal effect of the allosteric effectors AMP and fructose-2,6-bisphosphatase must be involved in the reaction network. The study of bisphosphatase. The attained states can either be glycolytic or gluconeogenic, their metabolic efficiencies depend mainly on the maximum activities of phosphofructokinase and fructose-1,6-bisphosphatase as well as on the supply of fructose-6-phosphate and fructose-1,6-bisphosphate. Efficient metabolic states arise only when both the enzyme concentrations and the rates of substrate supply favor either the glycolytic or the gluconeogenic mode of action. At medium maximum concentrations of the enzymes oscillations occur, in which glycolytic and gluconeogenic states are consecutively passed. A high rate of substrate cycling is observed only at the transitions between the functionally antagonistic phases of the periodicities. By this temporal organization the mean efficiency of the states is increased. The integration of fructose-2,6-bisphosphate as very sensitively acting activator of phosphofructokinase and inhibitor of fructose-1,6-bisphosphatase gives rise either to emergence of oscillations or of their extinction. Generally, the glycolytic mode is favored by this effector because of its stimulatory action on the phosphofructokinase activity.

Fructose-Bisphosphatase↗