Effect of Dietary Theophylline on Pyruvate Metabolism and Respiratory Activities in Liver Mitochondria

1972 ◽  
Vol 140 (4) ◽  
pp. 1472-1476 ◽  
Author(s):  
B. Friend ◽  
M. A. Mehlman ◽  
V. Devore ◽  
R. B. Tobin
Keyword(s):  
Liver Mitochondria ◽  
Pyruvate Metabolism

scholarly journals A re-evaluation of the role of mitochondrial pyruvate transport in the hormonal control of rat liver mitochondrial pyruvate metabolism

1984 ◽  
Vol 223 (3) ◽  
pp. 677-685 ◽  
Author(s):  
A P Halestrap ◽  
A E Armston
Keyword(s):  
Respiratory Chain ◽  
Hormonal Regulation ◽  
Hormone Treatment ◽  
Liver Mitochondria ◽  
Hormonal Control ◽  
Protonmotive Force ◽  
Pyruvate Metabolism ◽  
Carboxylase Activity ◽  
Computer Simulation Studies

The inhibitor of mitochondrial pyruvate transport alpha-cyano-beta-(1-phenylindol-3-yl)-acrylate was used to inhibit progressively pyruvate carboxylation by liver mitochondria from control and glucagon-treated rats. The data showed that, contrary to our previous conclusions [Halestrap (1978) Biochem. J. 172, 389-398], pyruvate transport could not regulate metabolism under these conditions. This was confirmed by measuring the intramitochondrial pyruvate concentration, which almost equilibrated with the extramitochondrial pyruvate concentration in control mitochondria, but was significantly decreased in mitochondria from glucagon-treated rats, where rates of pyruvate metabolism were elevated. Computer-simulation studies explain how this is compatible with linear Dixon plots of the inhibition of pyruvate metabolism by alpha-cyano-4-hydroxycinnamate. Parallel measurements of the mitochondrial membrane potential by using [3H]triphenylmethylphosphonium ions showed that it was elevated by about 3 mV after pretreatment of rats with both glucagon and phenylephrine. There was no significant change in the transmembrane pH gradient. It is shown that the increase in pyruvate metabolism can be explained by a stimulation of the respiratory chain, producing an elevation in the protonmotive force and a consequent rise in the intramitochondrial ATP/ADP ratio, which in turn increases pyruvate carboxylase activity. Mild inhibition of the respiratory chain with Amytal reversed the effects of hormone treatment on mitochondrial pyruvate metabolism and ATP concentrations, but not on citrulline synthesis. The significance of these observations for the hormonal regulation of gluconeogenesis from L-lactate in vivo is discussed.

scholarly journals Rat liver mitochondria prepared in mannitol media demonstrate increased mitochondrial volumes compared with mitochondria prepared in sucrose media. Relationship to the effect of glucagon on mitochondrial function

1984 ◽  
Vol 221 (1) ◽  
pp. 147-152 ◽  
Author(s):  
D E Whipps ◽  
A P Halestrap
Keyword(s):  
Liver Mitochondria ◽  
Mitochondrial Metabolism ◽  
Rat Liver Mitochondria ◽  
Pyruvate Metabolism ◽  
Succinate Oxidation ◽  
Isolation Medium ◽  
Matrix Volume ◽  
Sucrose Medium ◽  
Mitochondrial Volume ◽  
Citrulline Synthesis

Liver mitochondria isolated from glucagon-treated rats by using both mannitol- and sucrose-based media showed enhanced uncoupled succinate oxidation, pyruvate metabolism and citrulline synthesis. Mitochondria prepared in mannitol medium showed some stimulation of these parameters compared with those prepared in sucrose medium. This was accompanied by an increase in matrix volume of about 20%. Some [14C]mannitol became permanently associated with mitochondria during preparation. It is suggested that mannitol may enter mitochondria during their preparation and cause swelling. The presence of 4mM-phosphate in the sucrose isolation medium stimulated the same parameters as did glucagon treatment, and also caused an increase in matrix volume of about 20%. These results confirm the conclusion that the mitochondrial volume may be important in the regulation of mitochondrial metabolism. They contradict the conclusion of others [Siess (1983) Hoppe-Seyler's Z. Physiol. Chem. 364, 279-290, 835-838] that mannitol rather than sucrose should be used when studying hormonal effects on mitochondrial metabolism. Reasons for the discrepancies in the results between groups studying the effects of hormones on mitochondrial metabolism are discussed.

Nutritional and hormonal regulation of pyruvate metabolism in the liver.

1979 ◽  
Vol 236 (5) ◽  
pp. E501
Author(s):  
H G McDaniel
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Hormonal Regulation ◽  
Co2 Fixation ◽  
Fasting Glucose ◽  
Insulin Injection ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Pyruvate Metabolism ◽  
Fasted Rats

The effect of fasting, glucose, and glucagon injection on pyruvate metabolism of rat liver mitochondria was studied. Fasting for 24 h caused a) a twofold increase in mitochondrial pyruvate uptake, b) fivefold increase in CO2 fixation, and c) no change in pyruvate decarboxylation. Injection of glucose to fasted rats 2 h prior to preparation suppressed by one-half the increase in mitochondrial pyruvate uptake and CO2 fixation and increased hepatic pyruvate content. Injection of glucagon together with glucose abolished the depression of pyruvate uptake by glucose but did not prevent the decrease in mitochondrial CO2 fixation or hepatic ketone content caused by glucose alone. The effects of insulin injection resembled that of glucose in decreasing hepatic ketone content, but differed by increasing pyruvate uptake without much change in CO2 fixation. It is concluded that the increase in gluconeogenesis induced by fasting is due to an increase in pyruvate uptake and carboxylation by hepatic mitochondria. The latter is due to the increased mobilization and oxidation of fatty acids induced by reciprocal changes in insulin and glucagon.

Effect of Acylcarnitines on Pyruvate Metabolism in Liver Mitochondria from Thiamin-deficient Rats

1970 ◽  
Vol 100 (12) ◽  
pp. 1407-1413 ◽  
Author(s):  
R. J. Paquet ◽  
M. A. Mehlman ◽  
R. B. Tobin ◽  
E. M. Sporn
Keyword(s):  
Liver Mitochondria ◽  
Pyruvate Metabolism

scholarly journals Mechanism of hypoglycaemic action of methylenecyclopropylglycine

1989 ◽  
Vol 259 (3) ◽  
pp. 921-924 ◽  
Author(s):  
K Melde ◽  
H Buettner ◽  
W Boschert ◽  
H P O Wolf ◽  
S Ghisla
Keyword(s):  
Plasma Concentrations ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Toxic Metabolite ◽  
Beta Oxidation ◽  
Pyruvate Metabolism ◽  
Oral Ingestion ◽  
Chain Acyl ◽  
Branched Chain ◽  
Coa Thioesters

The effects of methylenecyclopropylglycine (MCPG), the lower homologue of hypoglycin A, on starved rats are described. Upon oral ingestion of MCPG (43 mg/kg), a 50% decrease in blood glucose compared with controls was observed after 4 h. The plasma concentrations of lactate and non-esterified fatty acids were substantially increased during this period. The activity of general acyl-CoA dehydrogenase from isolated rat liver mitochondria was not significantly changed. By contrast, the activity of 2-methyl-(branched-chain)-acyl-CoA dehydrogenase decreased by over 80%. The enzyme activity of enoyl-CoA hydratase (crotonase) from pig kidneys decreased by 80% on incubation with the hypothetically toxic metabolite of MCPG, methylenecyclopropylformyl-CoA. These results suggest that the inhibition spectrum of MCPG is quite different from that of hypoglycin A and that similar physiological effects might result from inhibition of different enzymes of beta-oxidation, e.g. hypoglycaemia and lacticacidemia. Accumulation of medium-chain acyl-CoA thioesters is probably at the origin of disturbances in pyruvate metabolism.

scholarly journals Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats

1978 ◽  
Vol 172 (3) ◽  
pp. 389-398 ◽  
Author(s):  
A P Halestrap
Keyword(s):  
Membrane Potential ◽  
Respiratory Chain ◽  
Maximum Rate ◽  
Liver Mitochondria ◽  
Ph Gradient ◽  
O2 Uptake ◽  
Pyruvate Metabolism ◽  
The Matrix ◽  
Stimulation Of

Glucagon treatment of rats allowed the isolation of liver mitochondria with enhanced rates of pyruvate metabolism measured in either sucrose or KCl media. No change in the activity of the pyruvate carrier itself was apparent, but under metabolizing conditions, use of the inhibitor of pyruvate transport, alpha-cyano-4-hydroxycinnamate, demonstrated that pyruvate transport limited the rate of pyruvate metabolism. The maximum rate of transport under metabolizing conditions was enhanced by glucagon treatment. Problems involved in measuring the transmembrane pH gradient under metabolizing conditions are discussed and a variety of techniques are used to estimate the matrix pH. From the distribution of methylamine, ammonia and D-lactate and the Ki for inhibition by alpha-cyano-4-hydroxycinnamate it is concluded that the matrix is more acid than the medium and that the pH of the matrix rises after glucagon treatment. The increase in matrix pH stimulates pyruvate transport. The membrane potential, ATP concentration and O2 uptake were also increased under metabolizing conditions in glucagon-treated mitochondria. These changes were correlated with a stimulation of the respiratory chain which can be observed in uncoupled mitochondria [Yamazaki (1975) J. Biol. Chem. 250, 7924–7930]. The mitochondrial Mg2+ content (mean +/- S.E.M.) was increased from 38.8 +/- 1.2 (n = 26) to 47.5 +/- 2.0 (n = 26) ng-atoms/mg by glucagon and the K+ content from 126.7 +/- 10.3 (n = 19) ng-atoms/mg. This may represent a change in membrane potential induced by glucagon in vivo. The physiological significance of these results in the control of gluconeogenesis is discussed.

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