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.

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 Metabolic effects of propionate in normal and vitamin B12-deficient rats

1971 ◽  
Vol 124 (3) ◽  
pp. 501-507 ◽  
Author(s):  
D. L. Williams ◽  
G. H. Spray ◽  
R. Hems ◽  
D. H. Williamson
Keyword(s):  
Vitamin B12 ◽  
Pyruvate Carboxylase ◽  
Ketone Bodies ◽  
Metabolic Effects ◽  
Acetyl Coa ◽  
Twofold Increase ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Absolute Decrease ◽  
Deficient Group

1. Administration of propionate caused a twofold increase in the concentrations of lactate and pyruvate in the blood of vitamin B12-deficient rats, whereas there was a slight decrease in lactate and a 50% increase in pyruvate in normal rats. 2. Concentrations of total ketone bodies in the blood of normal rats were not significantly altered by propionate administration but the [3-hydroxybutyrate]/[acetoacetate] ratio decreased from 3.0 to 2.0. In the vitamin B12-deficient rats there was a 40% decrease in total ketone bodies and a change in the ratio from 3.4 to 1.2. 3. The changes in the concentration of ketone bodies in freeze-clamped liver preparations were similar in pattern to those observed in blood. 4. Propionate administration caused a decrease in the concentration of acetyl-CoA in the livers of both groups of animals, but the absolute decrease was greater in the vitamin B12-deficient group. The decrease in the concentration of CoA was similar in both groups. 5. As in blood, there were threefold increases in the concentrations of lactate and pyruvate in the livers of the vitamin B12-deficient rats after propionate administration, whereas there was no significant change in the concentrations of these metabolites in the normal rats. 6. There was a 50% inhibition of glucose synthesis in perfused livers from vitamin B12-deficient rats when lactate and propionate were substrates as compared with lactate alone. 7. It is concluded that the conversion of lactate into glucose is inhibited in vitamin B12-deficient rats after propionate administration, and that this effect is due to inhibition of the pyruvate carboxylase step resulting from a decrease in acetyl-CoA concentration and a postulated increase in methylmalonyl-CoA concentration.

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.

Fatigue and phosphocreatine depletion during carbon dioxide-induced acidosis in rat muscle

1983 ◽  
Vol 245 (1) ◽  
pp. C15-C20 ◽  
Author(s):  
K. Sahlin ◽  
L. Edstrom ◽  
H. Sjoholm
Keyword(s):  
High Energy ◽  
Initial Value ◽  
High Co2 ◽  
Fourfold Increase ◽  
Control Value ◽  
Before And After ◽  
Phosphate Depletion ◽  
Creatine Kinase Equilibrium ◽  
Lactate And Pyruvate ◽  
Tetanic Tension

Isolated extensor digitorum longus muscles from rat were exposed to atmospheres of 30% CO2 (high-CO2 muscles) or 6.5% CO2 (control muscles) in O2 for 95 min. Muscle contraction characteristics were studied before and after the incubation. Tetanic tension decreased in high-CO2 muscles to 55% of initial value but remained unchanged in control muscles. Relaxation time was prolonged in high-CO2 muscles but not in control muscles. Intracellular pH was 6.67 +/- 0.04 (SD) in high-CO2 muscles and 7.01 +/- 0.04 in control muscles. CO2-induced acidosis had a marked influence on the intermediary energy metabolism as shown by a fourfold increase of glucose 6-phosphate, a 14% increase of ADP, and a decrease of phosphocreatine to 44% of the control value. Lactate and pyruvate contents were unchanged. The observed metabolic changes can be explained by an effect of H+ on the activity of phosphofructokinase and on the creatine kinase equilibrium. It can be concluded that H+ concentration causes muscular fatigue. It is, however, uncertain whether this is an effect of increased H+ per se or by high-energy phosphate depletion induced by acidosis.

scholarly journals Measurement of blood acetoacetate and β-hydroxybutyrate in an automatic analyser

2001 ◽  
Vol 23 (3) ◽  
pp. 69-76 ◽  
Author(s):  
Amparo Galán ◽  
Josém. Hernández ◽  
Orlando Jimenez
Keyword(s):  
Ethylenediaminetetraacetic Acid ◽  
Ketone Bodies ◽  
Mitochondrial Diseases ◽  
Turnaround Time ◽  
Sample Volume ◽  
Intermediary Metabolites ◽  
Transport Chain ◽  
Analytical Response ◽  
Lactate And Pyruvate ◽  
Blood Ketone Bodies

g-hydroxybutyrate and acetoacetate as well as lactate and pyruvate are intermediary metabolites normally present in blood. The g-hydroxybutyrate/acetoacetate ratio is an expression of the mitochondrial oxido-reduction state. This ketone body ratio can provide a clue to diagnosis and metabolic status in congenital errors of the electron transport chain and pyruvate metabolism. The standardization of these analytical procedures improves the interpretation of the results helping in the difficult diagnosis of mitochondrial diseases in children. This study describes an adaptation to a Dimension R 2 L (Dade Behring, Newark, Delaware, USA) automatic analyser for a method to measure blood ketone bodies (g-hydroxybutyrate and acetoacetate). The method allows the metabolites to be measured directly in nondeproteinized plasma (fluoride/ethylenediaminetetraacetic acid). This adaptation simplifies the analytical procedure and limits the turnaround time to 20 minutes. With a sample volume of 200 μ l metabolite concentrations ranging from 12 to 1300 μ molL−1of g-hydroxybutyrate and from 10 to 450 μ molL−1of acetoacetate may be measured with a reliable analytical response.

The Effect of Plasma from Schizophrenic Patients on the Chicken Erythrocyte System

1963 ◽  
Vol 109 (459) ◽  
pp. 231-234 ◽  
Author(s):  
A. Mangoni ◽  
R. Balazs ◽  
A. J. Coppen
Keyword(s):  
Carbohydrate Metabolism ◽  
Normal Subjects ◽  
Aerobic Metabolism ◽  
Red Cells ◽  
Chicken Erythrocyte ◽  
Schizophrenic Patients ◽  
Lactate And Pyruvate ◽  
Pyruvate Ratio

Frohman et al. (1960a, 1960b, 1961, 1962) have investigated the effect of plasma of schizophrenic patients on carbohydrate metabolism. They measured the production of lactate and pyruvate by the nucleated red cells of the chicken after incubation with patients' plasma. After incubation with plasma from schizophrenic patients, the lactate/pyruvate ratio was raised significantly above the ratio found after incubation with plasma from normal subjects. This observation was interpreted as evidence of an inhibition of aerobic metabolism induced by the plasma of schizophrenic patients. We report here an attempt to confirm these findings.

scholarly journals The metabolic effects of sodium dichloroacetate in the starved rat

1974 ◽  
Vol 142 (2) ◽  
pp. 279-286 ◽  
Author(s):  
Perry J. Blackshear ◽  
Paul A. H. Holloway ◽  
K. George M. M. Albert
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Metabolic Effects ◽  
Plasma Insulin Concentration ◽  
Hepatic Glucose ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Gluconeogenic Substrates ◽  
Net Release ◽  
Pyruvate Ratio

1. Sodium dichloroacetate (300mg/kg body wt. per h) was infused in 24h-starved rats for 4h. 2. Blood glucose decreased significantly, an effect that had previously only been noted in diabetic animals 3. Plasma insulin concentration decreased by 63% blood lactate and pyruvate concentrations decreased by 50 and 33%, whereas concentrations of 3-hydroxybutyrate and acetoacetate increased by 81 and 73% respectively. 4. Livers were freeze-clamped at the end of the 4h infusion. There were significant decreases in hepatic [glucose], [glucose 6-phosphate], [2-phosphoglycerate], the [lactate]/[pyruvate] ratio, [citrate] and [malate], and also [alanine], [glutamate] and [glutamine], suggesting a diminished supply of gluconeogenic substrates. 5. Animals subjected to a functional hepatectomy at the end of 2h infusions showed no difference in blood-glucose disappearance but a highly significant decrease in the rate of accumulation of lactate, pyruvate, glycerol and alanine, compared with control animals. Dichloroacetate decreased ketone-body clearance. 6. After functional hepatectomy an increase in glutamine accumulation appeared to compensate for the decrease in alanine accumulation. 7. It is concluded that dichloroacetate causes hypoglycaemia by decreasing the net release of gluconeogenic precursors from extrahepatic tissues while inhibiting peripheral ketone-body uptake. 8. These findings are consistent with the activation of pyruvate dehydrogenase (EC 1.2.4.1) in rat muscle by dichloroacetate previously described by Whitehouse & Randle (1973).

Phosphoenolpyruvate carboxylase activity from Avena coleoptile tissue. Regulation by H+ and malate

1978 ◽  
Vol 56 (4) ◽  
pp. 404-407 ◽  
Author(s):  
B. C. Hill ◽  
A. W. Bown
Keyword(s):  
Phosphoenolpyruvate Carboxylase ◽  
Enzyme System ◽  
Mass Action ◽  
Direct Inhibition ◽  
Carboxylase Activity ◽  
Pep Carboxylase ◽  
Action Effect ◽  
Avena Coleoptile ◽  
Oxaloacetic Acid ◽  
Regulatory Properties

Preparations of phosphoenolpyruvate (PEP) carboxylase activity from Avenu sativa coleoptile tissue were assayed by measuring the incorporation of labelled bicarbonate into a derivative of oxaloacetic acid or by coupling oxaloacetic acid production to malate dehydrogenase activity and the oxidation of NADH. Malate inhibition of PEP carboxylase activity was found to be noncompetitive, was not due to a mass action effect on the coupled enzyme system or to chelation of Mg2+, and probably involved direct inhibition of the enzyme by malate. Maximal PEP carboxylase activity was exhibited around pH 8.0 and increased 125% between pH 7.0 and pH 7.6. Inhibition by 4 mML-malate was virtually complete at pH 7.0 and decreased to 10% inhibition at pH 8. This information is discussed in the light of data which demonstrates that in response to IAA. coleoptile tissue accumulates malate and secretes H+. The regulatory properties of PEP carboxylase are consistent with a role in malate production which could resist increases in intracellular pH resulting from an auxin-stimulated H+ efflux.

scholarly journals Potentiation by ammonia of the metabolic effects of pent-4-enoate in isolated rat hepatocytes

1984 ◽  
Vol 224 (1) ◽  
pp. 263-267 ◽  
Author(s):  
F X Coudé ◽  
G Grimber ◽  
P Parvy ◽  
D Rabier ◽  
J Bardet
Keyword(s):  
Cellular Metabolism ◽  
Rat Hepatocytes ◽  
Metabolic Effects ◽  
Maximum Effect ◽  
Half Maximum ◽  
Isolated Rat Hepatocytes ◽  
Glucose Synthesis ◽  
Beta Hydroxybutyrate ◽  
Isolated Rat ◽  
Pyruvate Ratio

The metabolic effects of pent-4-enoate were studied in isolated rat hepatocytes; 1 mM-pent-4-enoate did not significantly inhibit gluconeogenesis from lactate, alanine and glycerol, but significantly decreased glucose synthesis from pyruvate. The addition of 1 mM-NH4Cl led to a drastic inhibition of glucose synthesis from all these substrates. In hepatocytes incubated with 10 mM-alanine and 1 mM-oleate, pent-4-enoate at 0.05-1 mM slightly inhibited glucose synthesis and ketogenesis. The addition of ammonia resulted in a dramatic potentiation of the metabolic effects of pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of ATP and acetyl-CoA were also decreased by the addition of ammonia, as were lactate/pyruvate ratio and beta-hydroxybutyrate/acetoacetate ratio. These data suggest that ammonia seriously interferes with the cellular metabolism of pent-4-enoate and leads to a dramatic potentiation of its effects.

Sign in / Sign up

Export Citation Format

Share Document