scholarly journals The effect of glycerol and dihydroxyacetone on hepatic adenine nucleotides

1973 ◽  
Vol 132 (1) ◽  
pp. 55-60 ◽  
Author(s):  
H. F. Woods ◽  
H. A. Krebs
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Phosphate Content ◽  
Perfusion Medium ◽  
Control Value ◽  
Lactate And Pyruvate ◽  
Metabolite Content ◽  
Pyruvate Ratio

1. The changes in the metabolite content in the isolated perfused rat liver and in the perfusion medium were measured after loading the liver with glycerol or dihydroxyacetone. 2. Glycerol was rapidly taken up by livers from fed and starved rats; glucose, lactate and pyruvate were discharged into the medium. The [lactate]/[pyruvate] ratio in the medium rose from 10 to 30 and in the tissue from 9.6 to 36.6. 3. The most striking effects of glycerol loading were: (i) the accumulation in the liver of α-glycerophosphate, which increased from 0.13 to 8.45μmol/g at 40min; (ii) the decrease in the concentration of adenine nucleotides to 70% of the control value at 40min. 4. The Pi content of the tissue also fell, from 4.25 to 2.31μmol/g at 10min, but the sum of the phosphates measured rose from the normal value of 13.8 to 18.8μmol/g at 40min, because of an uptake of Pi from the medium. 5. Omission of phosphate from the standard perfusion medium increased the depletion of adenine nucleotides on glycerol loading. 6. Dihydroxyacetone was more rapidly metabolized than glycerol. Again glucose, lactate and pyruvate were the main products. The [lactate]/[pyruvate] ratio remained below 10. 7. Dihydroxyacetone caused an increase of the fructose 1-phosphate content from 0.23 to 0.39μmol/g at 10min. The adenine nucleotide content of the tissue was not significantly decreased by dihydroxyacetone loading. 8. The rate of removal of both glycerol and dihydroxyacetone was about 60% greater in the livers from fed than in those from starved animals. 9. The results extend previous findings by Burch et al. (1970), who administered glycerol and dihydroxyacetone intraperitoneally.

scholarly journals Xylitol metabolism in the isolated perfused rat liver

1973 ◽  
Vol 134 (2) ◽  
pp. 437-443 ◽  
Author(s):  
H. F. Woods ◽  
H. A. Krebs
Keyword(s):  
Main Product ◽  
Adenine Nucleotides ◽  
Lactate Production ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Atp Content ◽  
Control Value ◽  
Lactate And Pyruvate ◽  
The Mean ◽  
Pyruvate Ratio

1. Loading the isolated perfused liver from well-fed rats with xylitol (20mm) caused a depletion of adenine nucleotides and Pi and an accumulation of α-glycerophosphate. The ATP content fell to 66% of the control value after 10min and to 32% after 80min. The ADP and AMP contents also fell. After 80min 63% of the total adenine nucleotides and 59% of the Pi had been lost. 2. The α-glycerophosphate content rose from 0.13 to 4.74μmol/g at 10min and reached 8.02μmol/g at 40min. 3. Xylitol was rapidly metabolized, the main products being glucose, lactate and pyruvate. 4. The [lactate]/[pyruvate] ratio in the presence of xylitol rose to 30–40. 5. On perfusion of livers from starved animals the main product of xylitol metabolism was glucose and the mean ratio xylitol removed/glucose formed was 1.29 (corrected for endogenous glucose and lactate production). This is close to the predicted value of 1.2. 6. Evidence is presented indicating that the loss of adenine nucleotides caused by xylitol is not due to the increased ATP consumption but to the accumulation of α-glycerophosphate and depletion of Pi. 7. The loss of adenine nucleotides accounts for the hyperuricaemia which can occur after xylitol infusion in man. 8. The relevance of the findings to the clinical use of xylitol as an energy source is discussed.

scholarly journals The cause of hepatic accumulation of fructose 1-phosphate on fructose loading

1970 ◽  
Vol 119 (3) ◽  
pp. 501-510 ◽  
Author(s):  
H. F. Woods ◽  
L. V. Eggleston ◽  
H. A. Krebs
Keyword(s):  
Adenine Nucleotides ◽  
Amp Deaminase ◽  
Atp Content ◽  
Perfusion Medium ◽  
Normal Value ◽  
Rate Of Penetration ◽  
Physiological Limits ◽  
Transient Decrease ◽  
Metabolite Content ◽  
Pyruvate Ratio

1. The changes in the metabolite content in freeze-clamped livers of fed rats occurring on perfusion with 10mm-d-fructose have been examined. 2. The most striking effects of fructose were an accumulation of fructose 1-phosphate, as already known, up to 8.7μmol/g of liver within 10min, a loss of total adenine nucleotides (up to 35% after 40min) with a decrease in the ATP content to 23% within 10min, a sevenfold rise in the concentration of IMP to 1.1μmol/g and an eightfold rise of α-glycerophosphate to 1.1μmol/g. 3. There was a transient decrease in Pi from 4.2 to 1.7μmol/g. Within 40min the Pi content recovered to the normal value, probably because of an uptake of Pi from the perfusion medium. 4. The degradation of the adenine nucleotides beyond the stage of AMP can be accounted for by the decrease of ATP and Pi. As ATP inhibits 5-nucleotidase, and as Pi inhibits AMP deaminase any AMP arising in the tissue is liable to undergo dephosphorylation or deamination under the conditions occurring after fructose loading. 5. The content of lactate increased to 4.3μmol/g at 80min; pyruvate also increased and the [lactate]/[pyruvate] ratio remained within physiological limits. 6. The concentration of free fructose within the liver remained much below that in the perfusion medium, indicating that the rate of penetration of fructose into the tissue was lower than the rate of utilization. 7. The fission of fructose 1-phosphate by liver aldolase is inhibited by several phosphorylated intermediates, especially by IMP. This inhibition is competitive with a Ki of 0.1mm. 8. The maximal rates of the enzymes synthesizing and splitting fructose 1-phosphate are about equal. The accumulation of fructose 1-phosphate on fructose loading is due to the inhibition of the fission of fructose 1-phosphate by the IMP arising from the degradation of the adenine nucleotides.

scholarly journals Metabolism of inorganic sulphate in the isolated perfused rat liver. Effect of sulphate concentration on the rate of sulphation by phenol sulphotransferase

1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Physiological Concentration ◽  
Sulphate Concentration ◽  
Inorganic Sulphate

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.

scholarly journals The effect of propionate on the metabolism of pyruvate and lactate in the perfused rat liver

1972 ◽  
Vol 127 (3) ◽  
pp. 539-543 ◽  
Author(s):  
T. M. Chan ◽  
R. A. Freedland
Keyword(s):  
Rat Liver ◽  
Sodium Butyrate ◽  
Perfused Rat Liver ◽  
Pyruvate Metabolism ◽  
Perfusion Medium ◽  
Lactate And Pyruvate ◽  
Sparing Effect

1. Rates of gluconeogenesis in the perfused rat liver from propionate, l-lactate, pyruvate and the combination of propionate with either lactate or pyruvate were measured. Less than additive rates were obtained with either propionate plus lactate or propionate plus pyruvate. 2. The uptake of pyruvate plus lactate from the perfusion medium was decreased more seriously when propionate was present with lactate than with pyruvate. 3. The use of [2-14C]pyruvate in the presence of propionate showed that the decreased disappearance of pyruvate plus lactate did not result in their formation from propionate. 4. The addition of sodium butyrate to the perfusion medium caused an inhibition of gluconeogenesis from propionate and stimulated gluconeogenesis and uptake of pyruvate and lactate. 5. The observations are consistent with there being a sparing effect of propionate on lactate and pyruvate metabolism.

scholarly journals Effects of stimulation by carbachol on the metabolism of the bovine adrenal medulla

1965 ◽  
Vol 97 (2) ◽  
pp. 555-560 ◽  
Author(s):  
P Banks
Keyword(s):  
Oxygen Consumption ◽  
Adrenal Gland ◽  
Adrenal Medulla ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Great Decrease ◽  
Chromaffin Granules ◽  
Tyrode Solution ◽  
Spontaneous Release ◽  
Perfusion Medium

1. A method is described that has made it possible to achieve a great decrease in the catecholamine and adenine nucleotide contents of the perfused bovine adrenal gland by the infusion of carbachol. 2. Although the catecholamines secreted were recovered in the perfusion medium, no evidence was obtained that the nucleotides are secreted by the gland. 3. It is concluded that the secretion of catecholamines is accompanied by extensive chemical alteration of the adenine nucleotides of the chromaffin granules. 4. The secretory response and the spontaneous release of catecholamines depends on the presence of Ca(2+) in the perfusing Tyrode solution. 5. Anoxia does not have a significant effect on the carbachol-induced secretion of catecholamines. 6. Strips of bovine adrenal medullary tissue perfused with oxygenated Tyrode solution show an increased oxygen consumption when carbachol is added.

Energy status of the rat lung after exposure to elevated PO2

1978 ◽  
Vol 45 (1) ◽  
pp. 56-59 ◽  
Author(s):  
A. B. Fisher
Keyword(s):  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Rat Lung ◽  
Energy Status ◽  
Hyperoxic Exposure ◽  
Isolated Lung ◽  
Lactate And Pyruvate

To study hyperoxic effects on adenine nucleotide content and lactate and pyruvate production by lungs, rats were exposed to oxygen at 1 ATA for 18, 24, or 48 h or to 4 ATA for 1 h. Subsequently, lungs were removed from rats, placed in an isolated-lung apparatus, ventilated with 5% CO2 in O2, and perfused with Krebs-Ringer bicarbonate medium containing 5.5 mM glucose and 4% bovine serum albumin. Uptake of serotonin from the perfusate was depressed 28% in rats exposed to hyperbaric oxygen compared with unexposed controls. Concentrations of adenine nucleotides, the ATP/ADP ratio, and the “energy charge” were similar in control and oxygen-exposed rats. The production of lactate and the ratio of lactate to pyruvate production were significantly higher in rats exposed to oxygen for 48 h compared with other exposure regimens. Comparison of these results with those previously reported for serotonin uptake in lungs after hyperoxic exposure indicates that serotonin clearance is depressed prior to alteration of the energy status of the rat lung.

scholarly journals Metabolic studies in experimental liver disease resulting from d(+)-galactosamine administration

1972 ◽  
Vol 130 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Christopher O. Record ◽  
K. G. M. M. Alberti ◽  
Dermot H. Williamson
Keyword(s):  
Phosphoenolpyruvate Carboxylase ◽  
Ketone Bodies ◽  
Soluble Fraction ◽  
Mass Action ◽  
Significant Elevation ◽  
Control Value ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Experimental Liver ◽  
Pyruvate Ratio

1. In confirmation of previous work, administration of d(+)-galactosamine (0.5–0.75g/kg body wt.) to rats caused a hepatitis with histological evidence of liver damage and a 9-fold rise in aspartate aminotransferase activity in serum. 2. There was a significant elevation of blood lactate and pyruvate concentrations in 24h-starved rats treated with galactosamine but no change in the [lactate]/[pyruvate] ratio. 3-Hydroxybutyrate and acetoacetate concentrations in blood were decreased. 3. The changes in the concentrations of lactate, pyruvate and ketone bodies in the freeze-clamped liver were parallel to those observed in the blood. 4. In the livers of 24h-starved galactosamine-treated rats there were large increases in the concentrations of alanine (3-fold), citrate (5-fold), 2-oxoglutarate (4-fold), with smaller increases in malate, glutamate and aspartate. There was a 4-fold rise in the value of the mass-action ratio of the alanine aminotransferase system in the livers of galactosamine-treated rats when compared to controls. 5. There was a significant decrease in the activities of aspartate and alanine aminotransferases in the cytoplasm and the soluble fraction of sonicated homogenates of the livers of rats treated with galactosamine. The activity of phosphoenolpyruvate carboxylase was decreased by 75% of the control value. 6. Glucose synthesis from lactate in perfused livers from galactosamine-treated rats was inhibited 39% when compared with controls. 7. The results indicate that the conversion of lactate into glucose is decreased in the livers of galactosamine-treated rats and that this decrease may be due to the loss of phosphoenolpyruvate carboxylase from damaged hepatocytes.

Effects of tolbutamide on gluconeogenesis and glycolysis in isolated perfused rat liver

1986 ◽  
Vol 250 (1) ◽  
pp. E82-E86
Author(s):  
T. B. Patel
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Hepatic Metabolism ◽  
Tricarboxylic Acid ◽  
Isolated Perfused Rat Liver ◽  
Perfusion Medium ◽  
14Co2 Production ◽  
Lactate And Pyruvate ◽  
Fasted Rats

In isolated perfused livers of 24-h fasted rats, perfused with lactate (2 mM), pyruvate (0.5 mM), or dihydroxyacetone (1 mM), infusion of tolbutamide (0.5 mM) very rapidly (within 3 min) inhibited the rate of gluconeogenesis. However, gluconeogenesis from fructose (1 mM) and glycerol (1 mM) was not affected by tolbutamide. Tolbutamide also inhibited by 30% the rate of 14CO2 production from livers perfused with [1-14C]pyruvate, without altering the rate of 14CO2 production from [2-14C]pyruvate. The rate of hepatic glycolysis from fructose, glycerol, and dihydroxyacetone was also stimulated by 250, 40, and 100%, respectively, during tolbutamide infusion into perfused livers. Tolbutamide also inhibited the endogenous rate of hepatic ketogenesis by 30%. All of the tolbutamide-mediated alterations in hepatic metabolism were reversed upon withdrawal of tolbutamide from the perfusion medium. Decreased hepatic gluconeogenesis from lactate and pyruvate in the presence of tolbutamide was not a consequence of increased pyruvate oxidation via the pyruvate dehydrogenase complex or the tricarboxylic acid cycle.

Bile Acid Metabolism in Mammals. V. Studies on the Sex Difference in the Response of the Isolated Perfused Rat Liver to Chenodeoxycholic Acid

1973 ◽  
Vol 51 (6) ◽  
pp. 418-423 ◽  
Author(s):  
I. M. Yousef ◽  
R. Magnusson ◽  
V. M. Price ◽  
M. M. Fisher
Keyword(s):  
Bile Acid ◽  
Sex Difference ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Bile Acid Metabolism ◽  
Isolated Perfused Rat Liver ◽  
Base Line ◽  
Female Rat ◽  
Perfused Rat Liver ◽  
Perfusion Medium

The hepatic metabolism of chenodeoxycholic acid (CDCA) was studied using the isolated perfused rat liver technique. In 12 perfusions, six male and six female, 30 μmol of CDCA were added to the perfusion medium, and in 12 other perfusions, also six of each sex, 1 μmol of CDCA was added to the perfusion medium. The CDCA was added after 2 h of base-line perfusion and the bile acids of liver, plasma, and bile were analyzed by combined thin-layer and gas chromatography. In the 2 h of perfusion prior to the addition of exogenous CDCA there were sex differences in the kinetics of bile acid secretion in the bile and in the bile acid composition of that bile. Following the addition of CDCA to the perfusion medium the female liver was found to take up more CDCA from the perfusion medium, to store more CDCA, and to convert less CDCA to β-muricholic acid. It was documented that the toxicity of CDCA for the isolated perfused liver of the female rat is not due to α- or β-muricholic acid, the end products of CDCA metabolism in the rat. The relatively greater capacity of the male liver to convert potentially toxic CDCA to nontoxic β-muricholic acid may explain, at least in part, the observed sex difference in CDCA hepatotoxicity.

Effect of glycogenolytic agents on phosphorylase activity of perfused rat liver

1965 ◽  
Vol 208 (2) ◽  
pp. 317-323 ◽  
Author(s):  
Robert A. Levine
Keyword(s):  
Rat Liver ◽  
Cyclic Nucleotide ◽  
Adenine Nucleotides ◽  
Adenosine Monophosphate ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Adrenocorticotrophic Hormone ◽  
Phosphorylase Activity ◽  
Glycogen Breakdown ◽  
Intact Rats

The effect of glycogenolytic agents on phosphorylase activity has been studied in the isolated perfused rat liver. Evidence is presented showing that endoportal administration of 10–6m glucagon, 10–5 m epinephrine, and 10–3 M cyclic 3',5'-adenosine monophosphate (3',5'-AMP) induced glycogenolysis, hyperglycemia, and increase in liver phosphorylase activity, usually within 1 hr after the onset of infusion. ATP, 10–3m, also caused glycogenolysis, but the onset was slower than with the cyclic nucleotide, and phosphorylase activation was inconstant Hyperglycemic effects of these two adenine nucleotides were also demonstrated in intact rats. Anoxia and hypoxia caused substantial glycogenolysis but did not stimulate phosphorylase activity, implying that some other mechanism accounts for the glycogen breakdown induced by reduced oxygen tension. Glycogenolysis and phosphorylase activation were not produced by administration of 10–2 M 5'-AMP, 10–4 M isoproterenol, adrenocorticotrophic hormone, or insulin.

Sign in / Sign up

Export Citation Format

Share Document