scholarly journals The relation of sodium and potassium ion transport to the respiration and adenine nucleotide content of liver slices treated with inhibitors of respiration

1972 ◽  
Vol 129 (2) ◽  
pp. 427-438 ◽  
Author(s):  
G. D. V. Van Rossum
Keyword(s):  
Ion Transport ◽  
Concentration Ratio ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Critical Value ◽  
Endogenous Respiration ◽  
Atp Content ◽  
Nucleotide Content ◽  
Liver Slices ◽  
Potassium Ion Transport

1. The dependence of the net transport of Na+and K+by rat liver on the respiration has been determined by incubating slices in the presence of varying concentrations of respiratory inhibitors. 2. Neither the rate of net transport nor the total amount of each ion transported was inhibited unless the rate of endogenous respiration was decreased below a critical value of about 330mmol of O2/h per kg of protein (i.e. 50% of the total endogenous respiration). 3. The uninhibited rate of respiration could be varied over a twofold range (380–770mmol of O2/h per kg of protein) by the use of different substrates, but the critical value for the onset of transport inhibition was quite constant (290–360mmol/h per kg of protein) under these different conditions. 4. Slices incubated at 38°C without inhibitors showed an increase of their ATP content and the concentration ratio ATP/ADP. The final ATP content and concentration ratio, ATP/ADP, of slices treated with different concentrations of inhibitors were closely related to the rate of respiration. 5. The increased ATP content of the control slices during incubation was equal to the increase of total adenine nucleotides. At increasing degrees of respiratory inhibition the relative contributions of ADP and AMP to the total adenine nucleotide content increased. 6. The critical rate of respiration for the onset of inhibition of ion transport and the corresponding contents of adenine nucleotides provide estimates of the maximal values of certain parameters of energy metabolism required for the support of alkali-cation transport in the liver slices.

Regulation of mitochondrial adenine nucleotide content in newborn rabbit liver

1987 ◽  
Vol 253 (5) ◽  
pp. E530-E535 ◽  
Author(s):  
P. C. Tullson ◽  
J. R. Aprille
Keyword(s):  
Concentration Ratio ◽  
Tissue Oxygenation ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Postnatal Period ◽  
Rabbit Liver ◽  
Hormonal Changes ◽  
Nucleotide Content ◽  
Normal Increase ◽  
Beta Hydroxybutyrate

This study examined the relationship between postnatal metabolic and hormonal changes and the accompanying rapid increase in mitochondrial adenine nucleotide content (ATP + ADP + AMP) in rabbit liver. The cytosolic NAD+/NADH concentration ratio, calculated from tissue pyruvate and lactate values, increased linearly 6.6-fold during the 1st postnatal h. The mitochondrial NAD+/NADH concentration ratio, calculated from tissue acetoacetate and beta-hydroxybutyrate values, increased 28-fold by 30 min postnatal. These changes in NAD+/NADH suggest that tissue oxygenation occurs rapidly and that oxygen supply rather than substrate supply is limiting for mitochondrial respiration in the immediate postnatal period. The normal increase in mitochondrial adenine nucleotide content that occurs within 2 h after birth was inhibited by hypoxia (5% O2). Glucagon stimulated the postnatal increase in mitochondrial adenine nucleotides but had no effect in combination with hypoxia. Both glucose and somatostatin injections inhibited the increase in mitochondrial adenine nucleotides and increased the insulin-to-glucagon ratio. Isoproterenol or dibutyryl cAMP stimulated, but propranolol did not inhibit, the normal increase in mitochondrial adenine nucleotide content. Phentolamine did not stimulate the postnatal accumulation of adenine nucleotides. In summary, the results show that the insulin-to-glucagon ratio is probably the most important hormone regulator of the rapid recompartmentation of adenine nucleotides into the mitochondrial matrix and that tissue oxygenation is strictly permissive for this hormone effect in the first 2 h after birth.

Regulation of hepatic gluconeogenesis in newborn rabbit: controlling factors in presuckling period

1985 ◽  
Vol 249 (5) ◽  
pp. E498-E505 ◽  
Author(s):  
W. A. Brennan ◽  
J. R. Aprille
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Mitochondrial Protein ◽  
Fold Increase ◽  
Insulin Injection ◽  
Pyruvate Carboxylation ◽  
Glucose Levels ◽  
Newborn Rabbit ◽  
Nucleotide Content

We have previously shown (Comp. Biochem. Physiol. 77B: 35-39, 1984) that a rapid postnatal increase in hepatic mitochondrial adenine nucleotide content activates pyruvate carboxylation and gluconeogenesis in the newborn rabbit. This study investigated factors limiting flux through the gluconeogenic pathway and examined the physiological stimuli responsible for the activation phenomenon. There is a 2.3-fold increase in total mitochondrial adenine nucleotides, along with a threefold increase in the matrix ATP/ADP ratio, by 2 h after birth, resulting overall in a sixfold increase in the amount of ATP/mg mitochondrial protein. Analysis of gluconeogenic intermediates, measured in freeze-clamped livers between birth and 4 h postnatal, suggests that pyruvate carboxylase controls gluconeogenic flux during this period. Newborn rabbits reared in an hypoxic environment (5% O2) exhibited decreased mitochondrial adenine nucleotide content, decreased rates of pyruvate carboxylation, and depressed blood glucose levels compared with littermates reared in room air or 95% O2. Manipulation of the insulin-to-glucagon ratio in vivo by injecting insulin at birth significantly delayed postnatal increases in the mitochondrial adenine nucleotide content and the rate of pyruvate carboxylation. Conversely, glucagon injection produced a supranormal increase in both mitochondrial adenine nucleotide content and pyruvate carboxylation. In addition, insulin injection prevented, whereas glucagon enhanced, the normal postnatal increase in tissue ATP/ADP. These results suggest that tissue oxygenation and a decreased insulin-to-glucagon ratio promote the rapid influx of adenine nucleotides from the liver cytosol into the mitochondrial matrix, thereby activating pyruvate carboxylation and gluconeogenesis during the presuckling period.

Adenine Nucleotides in Platelets from Normal and Uraemic Subjects

1968 ◽  
Vol 19 (01/02) ◽  
pp. 036-040 ◽  
Author(s):  
W. R Pitney ◽  
H Hinterberger ◽  
M Potter
Keyword(s):  
Glass Bead ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Blood Samples ◽  
Nucleotide Content ◽  
Before And After

SummaryAdenine nucleotides in platelets from normal and uraemic subjects were measured before and after passage of blood through glass bead filters. Platelets from uraemic subjects contained normal amounts of ATP, ADP, AMP and total nucleotides. Normal platelets which had passed through filters contained higher concentrations of ATP, ADP and total nucleotides than platelets in control blood samples, indicating either heterogeneity of adenine nucleotide content in normal platelets or possibly adsorption of nucleotides onto platelets during their passage through the filters. This phenomenon was not observed with platelets from uraemic patients.

Effects of Inhibitors of Metabolism on Adenine Nucleotides and on 22Na and 42K and Net Movements in Rat Uteri at 25 °C

1971 ◽  
Vol 49 (3) ◽  
pp. 205-239 ◽  
Author(s):  
E. E. Daniel ◽  
Kathleen Robinson
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Atp Depletion ◽  
Atp Content ◽  
Sodium Efflux ◽  
Cellular Fraction ◽  
Glucose Depletion ◽  
Na Efflux ◽  
Per Se

The effects of 10−3 M iodoacetate (IAA) and (or) 10−3 M dinitrophenol (DNP) on Na and K fluxes and contents and on adenine nucleotide levels of isolated rat uterine horns were studied. Early 22Na efflux was slightly increased by DNP in the fresh and Na-rich tissues. IAA and DNP alone or together reduced 22Na efflux from the larger cellular fraction (No. 2) in both fresh and Na-rich tissues. 22Na efflux from the smaller cellular fraction (No. 3) was accelerated by IAA and by DNP in Na-rich tissues. DNP increased 22Na influx in both types of tissue and caused net Na gain and K loss. In fresh tissues IAA or IAA plus DNP accelerated 22Na influx, but slowed this influx in Na-rich tissues. In fresh tissues the ATP content was reduced by 50% by DNP. After a 60-min exposure with IAA and a 15- to 20-min exposure with IAA plus DNP, the ATP levels were negligible. The onsets of action of IAA or of IAA plus DNP on Na fluxes were correlated with ATP depletion, but early acceleration of 22Na efflux by DNP was not. In fresh tissues 42K influx was slightly decreased at the time of ATP depletion and the influx was further slowed as tissue potassium was replaced by sodium. IAA plus DNP increased K efflux in 10 min and IAA alone increased K efflux after 100 min. Thus K flux changes were not well correlated with ATP depletion. Substitution of K for all the sodium in the bathing media did not alter the quality of the effects of IAA or IAA plus DNP on sodium efflux. When prolonged glucose depletion eliminated ATP and ADP, the effects of IAA could not be duplicated. But IAA alone, or with DNP, still caused alterations in the 22Na efflux. Therefore IAA acted on ion fluxes by a mechanism other than ATP depletion. Both fresh and Na-rich tissues swelled after ATP depletion. An effect on internal osmotic pressure rather than ATP-depletion per se was postulated. Other studies showed that Na-rich tissues were resistant to shrinking by hypertonic sucrose and became more so secondarily after ATP depletion because of increased sucrose permeability. Evidence from studies of swelling, as well as flux data, suggested that at least two Na pumps were present. Both were ATP-dependent. One was ouabain-sensitive and exchanged Na for K, while the other was ouabain-insensitive and controlled movement of Na with water.

scholarly journals Effect of adenosine on the adenine nucleotide content and metabolism of hepatocytes

1975 ◽  
Vol 152 (3) ◽  
pp. 593-599 ◽  
Author(s):  
P Lund ◽  
N W Cornell ◽  
H A Krebs
Keyword(s):  
Time Course ◽  
Ketone Bodies ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Adenosine Kinase ◽  
Urea Synthesis ◽  
O2 Consumption ◽  
Nucleotide Content ◽  
Adenosine Concentration ◽  
Glucose Formation

ADENOSINE (0.5 MM) added to hepatocyte suspensions increased the intracellular concentration of ATP and total adenine nucleotides within 60 min up to three-fold. 2. Adenosine at 0.5 mM inhibited gluconeogenesis from lactate by about 50%. At higher adenosine concentrations the inhibition was less. There was no strict parallelism between the time-course of the increase of the adenine nucleotide content and the time-course of the inhibition of gluconeogenesis from lactate. 3. Adenosine abolished the accelerating effects of oleate and dibutyryl cyclic AMP on gluconeogenesis from lactate. 4. Gluconeogenesis was no significant effect of adenosine with fructose, dihydroxyacetone or glycerol. With asparagine, adenosine caused anacceleration of glucose formation. 5. Adenosine incorporation into adenine nucleotides accounted for about 20% of the adenosine removal. 6. Inosine, hypoxanthine or adenine compared with adenosine gave relatively slight increases of adenine nucleotides. 7. Urea synthesis from NH4Cl under optimum conditions i.e. in the presence of ornithine, lactate and oleate, was also inhibited by adenosine. The inhibition increased with the adenosine concentration and was 65% at 4 mM-adenosine. Again there was no correlation between the degree of inhibition of urea synthesis and the increase in the adenine nucleotide content. 8. The basal O2 consumption, the increased O2 consumption on the addition of oleate and the rate of formation of ketone bodies were not affected by the addition of adenosine. The [β-hydroxybutyrate]/[acetoacetate] ratio was increased by adenosine, provided that lactate was present. 9. The increase of the adenine nucleotide content of the hepatocytes on the addition of adenosine may be explained on the assumption that adenosine kinase is not regulated by feedback but by substrate supply.

Adenine nucleotide synthesis from inosine during normoxia and after ischaemia in the isolated perfused rat heart

1985 ◽  
Vol 63 (9) ◽  
pp. 1159-1164 ◽  
Author(s):  
J. Aussedat ◽  
M. Verdys ◽  
A. Rossi
Keyword(s):  
Rat Heart ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Low Flow ◽  
Nucleotide Synthesis ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Nucleotide Content ◽  
Glycogen Stores

[14C]inosine in a range of concentrations of 20 μM to 1 mM was administered-to the isolated perfused rat heart for 30 min. The incorporation of the nucleoside into myocardial adenine nucleotides increased for extracellular concentrations of the precursor up to 50 μM, reaching a plateau at 60 nmol∙g−1∙30 min−1 with concentrations ranging between 50 and 200 μM. The supply of 500 μM and 1 mM of inosine induced a further increase in cardiac adenine nucleotide synthesis to about 200 nmol∙g−1∙30 min−1. When supplied during low flow ischaemia (0.5 mL∙min−1, 30 min.), 1 mM of inosine protected the heart against ATP degradation, while 100 μM of inosine was inefficacious. In the presence of 1 mM of inosine on reperfusion the adenine nucleotide content of the heart was similar to that observed in the absence of the nucleoside. The incorporation of [14C]inosine into adenine nucleotides was, in this last condition, below the value measured before ischaemia. Inosine administration was effective in protecting the heart against ischaemic breakdown of glycogen and favoured postischaemic restoration of glycogen stores.

Regulation of the mitochondrial ATP-Mg/Pi carrier in isolated hepatocytes

1993 ◽  
Vol 264 (3) ◽  
pp. C663-C670 ◽  
Author(s):  
D. T. Dransfield ◽  
J. R. Aprille
Keyword(s):  
Subcellular Distribution ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Isolated Hepatocytes ◽  
Cellular Regulation ◽  
Intact Cells ◽  
Nucleotide Content ◽  
Dose Dependent

This study investigated the cellular regulation of net adenine nucleotide movements between the cytoplasm and mitochondria in intact cells. Such movements are presumed to occur primarily by ATP-Mg exchange with Pi via the mitochondrial ATP-Mg/Pi carrier. Vasopressin, A23187, and thapsigargin all elevate intracellular free [Ca2+] and all caused dose-dependent increases in the mitochondrial adenine nucleotide content (29, 63, and 39%, respectively). Phorbol 12-myristate 13-acetate had no effect. The effect of vasopressin was abolished when cytoplasmic [ATP] was decreased (by 43%) and [Pi] was increased (3-fold) by addition of carboxyatractyloside. The effect of thapsigargin was abolished by addition of xylulose to deplete cytoplasmic [ATP] (by 50%) and [Pi] (> 4-fold). The results indicate that in intact cells Ca2+ activates the mitochondrial ATP-Mg/Pi carrier to enable changes in the subcellular distribution of adenine nucleotides and that the relative [ATP] and [Pi] gradients govern the direction and magnitude of net adenine nucleotide movements between the cytoplasm and mitochondria.

The Energy Metabolism of Novikoff Ascites Hepatoma Cells. I. The Effects of Glucose on the Intracellular Level of Adenine Nucleotides

1971 ◽  
Vol 49 (6) ◽  
pp. 686-694 ◽  
Author(s):  
J. W. Gurd ◽  
P. G. Scholefield
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Rapid Decrease ◽  
Intracellular Level ◽  
Atp Content ◽  
Ascites Tumor ◽  
Ascites Hepatoma ◽  
Novikoff Hepatoma ◽  
Adenosine Phosphates ◽  
Layer Chromatography

When freshly prepared Novikoff hepatoma ascites tumor cells were incubated with glucose there was a rapid decrease in the ATP content of the cells. This was initially accompanied by an increased level of ADP but in the interval 6–10 min after the addition of glucose only 40% of the original adenine nucleotide content could be accounted for as adenosine phosphates. Analysis by thin-layer chromatography indicated breakdown via inosine 5′-phosphate (IMP), inosine, and hypoxanthine. Continued incubation led to resynthesis from hypoxanthine to IMP and thence to the adenine nucleotides.

Permeability transition in rat liver mitochondria is modulated by the ATP-Mg/Pi carrier

2003 ◽  
Vol 285 (2) ◽  
pp. G274-G281 ◽  
Author(s):  
Thilo Hagen ◽  
Christopher J. Lagace ◽  
Josephine S. Modica-Napolitano ◽  
June R. Aprille
Keyword(s):  
Rat Liver ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Permeability ◽  
Nucleotide Content ◽  
Adenine Nucleotide Pool

Mitochondrial permeability transition, due to opening of the permeability transition pore (PTP), is triggered by Ca2+ in conjunction with an inducing agent such as phosphate. However, incubation of rat liver mitochondria in the presence of low micromolar concentrations of Ca2+ and millimolar concentrations of phosphate is known to also cause net efflux of matrix adenine nucleotides via the ATP-Mg/Pi carrier. This raises the possibility that adenine nucleotide depletion through this mechanism contributes to mitochondrial permeability transition. Results of this study show that phosphate-induced opening of the mitochondrial PTP is, at least in part, secondary to depletion of the intramitochondrial adenine nucleotide content via the ATP-Mg/Pi carrier. Delaying net adenine nucleotide efflux from mitochondria also delays the onset of phosphate-induced PTP opening. Moreover, mitochondria that are depleted of matrix adenine nucleotides via the ATP-Mg/Pi carrier show highly increased susceptibility to swelling induced by high Ca2+ concentration, atractyloside, and the prooxidant tert-butylhydroperoxide. Thus the ATPMg/Pi carrier, by regulating the matrix adenine nucleotide content, can modulate the sensitivity of rat liver mitochondria to undergo permeability transition. This has important implications for hepatocytes under cellular conditions in which the intramitochondrial adenine nucleotide pool size is depleted, such as in hypoxia or ischemia, or during reperfusion when the mitochondria are exposed to increased oxidative stress.

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