Measuring Mitochondrial Pyruvate Oxidation

2017 ◽  
pp. 321-338
Author(s):  
Lawrence R. Gray ◽  
Alix A. J. Rouault ◽  
Lalita Oonthonpan ◽  
Adam J. Rauckhorst ◽  
Julien A. Sebag ◽  
...  
Keyword(s):  
Pyruvate Oxidation

scholarly journals INHIBITORY ACTION OF meso-TARTRATE ON PYRUVATE OXIDATION

1955 ◽  
Vol 214 (1) ◽  
pp. 245-250
Author(s):  
J.H. Quastel ◽  
P.G. Scholefield
Keyword(s):  
Inhibitory Action ◽  
Pyruvate Oxidation

scholarly journals E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity

2016 ◽  
Vol 113 (39) ◽  
pp. 10998-11003 ◽  
Author(s):  
Matthieu Lacroix ◽  
Geneviève Rodier ◽  
Olivier Kirsh ◽  
Thibault Houles ◽  
Hélène Delpech ◽  
...  
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Energy Demand ◽  
Clinical Symptoms ◽  
Tricarboxylic Acid Cycle ◽  
Striated Muscles ◽  
Pyruvate Oxidation ◽  
Mitochondrial Pyruvate Carrier ◽  
Lactic Acidemia ◽  
Transcription Factor 1 ◽  
Dihydrolipoyl Dehydrogenase

The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC.

Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis

2021 ◽  
Author(s):  
I. F. Duarte ◽  
J. Caio ◽  
M. F. Moedas ◽  
L. A. Rodrigues ◽  
A. P. Leandro ◽  
...  
Keyword(s):  
Dihydrolipoamide Dehydrogenase ◽  
Pyruvate Oxidation

scholarly journals Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia

2000 ◽  
Vol 278 (3) ◽  
pp. E522-E534 ◽  
Author(s):  
Michelle L. Parolin ◽  
Lawrence L. Spriet ◽  
Eric Hultman ◽  
Melanie G. Hollidge-Horvat ◽  
Norman L. Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Phosphorylase ◽  
Lactate Production ◽  
Muscle Metabolism ◽  
Lactate Accumulation ◽  
Pyruvate Oxidation ◽  
Reduced Rate ◽  
Rate Limiting ◽  
Muscle Biopsies ◽  
Elevated Lactate

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O2 (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free Pi, in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDHa) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [Pi]. At the end of exercise, PDHawas greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.

scholarly journals Glucose metabolism in perfused skeletal muscle. Pyruvate dehydrogenase activity in starvation, diabetes and exercise

1976 ◽  
Vol 158 (2) ◽  
pp. 203-210 ◽  
Author(s):  
S A Hagg ◽  
S I Taylor ◽  
N B Ruberman
Keyword(s):  
Skeletal Muscle ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Preceding Paper ◽  
Diabetic Rats ◽  
Pyruvate Dehydrogenase Kinase ◽  
Lactate Oxidation ◽  
Pyruvate Oxidation ◽  
Measured Activity ◽  
Exercise Induced

1. The interconversion of pyruvate dehydrogenase between its inactive phosphorylated and active dephosphorylated forms was studied in skeletal muscle. 2. Exercise, induced by electrical stimulation of the sciatic nerve (5/s), increased the measured activity of (active) pyruvate dehydrogenase threefold in intact anaesthetized rated within 2 min. No further increase was seen after 15 min of stimulation. 3. In the perfused rat hindquarter, (active) pyruvate dehydrogenase activity was decreased by 50% in muscle of starved and diabetic rats. Exercise produced a twofold increase in its activity in all groups; however, the relative differences between fed, starved and diabetic groups persisted. 4. Perfusion of muslce with acetoacetate (2 mM) decreased (active) pyruvate dehydrogenase activity by 50% at rest but not during exercise. 5. Whole-tissue concentrations of pyruvate and citrate, inhibitors of (active) pyruvate dehydrogenase kinase and (inactive) pyruvate dehydrogenase phosphate phosphatase respectively, were not altered by excerise. A decrease in the ATP/ADP ratio was observed, but did not appear to be sufficient to account for the increase in (active) pyruvate dehydrogenase activity. 6. The results suggest that interconversion of the phosphorylated and dephosphorylated forms of pyruvate dehydrogenase plays a major role in the regulation of pyruvate oxidation by eomparison of enzyme activity with measurements of lactate oxidation in the perfused hindquarter [see the preceding paper, Berger et al. (1976)] suggest that pyruvate oxidation is also modulated by the concentrations of substrates, cofactors and inhibitors of (active) pyruvate dehydrogenase activity.

METABOLISM OF [2-14C] PYRUVATE IN NORMAL, ACROMEGALIC AND HGH-TREATED HUMAN SUBJECTS

1970 ◽  
Vol 65 (1) ◽  
pp. 155-169 ◽  
Author(s):  
W. W. Shreeve ◽  
E. Cerasi ◽  
R. Luft
Keyword(s):  
Glucose Tolerance ◽  
Marked Reduction ◽  
Human Subjects ◽  
Insulin Response ◽  
Human Growth ◽  
Pyruvate Oxidation ◽  
High Insulin ◽  
Low Glucose ◽  
Insulin Response To Glucose ◽  
The Mean

ABSTRACT In 4 studies on 3 acromegalic patients, who had normal iv glucose tolerance and high insulin response to infused glucose (Al), the oxidation to 14CO2 of [2-14C] pyruvate (injected intravenously in trace amount after overnight fast) was not different from that in 9 studies of 9 nonacromegalic »high insulin responders« (Ni). In 4 studies on 3 other acromegalic patients, who had low glucose tolerance and less insulin response to glucose (A2), the formation of 14CO2 was reduced to ½–⅔ that of Al or N1 and was about proportionate to the reduction in glucose tolerance. In A2 the 14CO2 formation was slightly lower than the mean for 10 studies with 7 non-acromegalic subjects, who were »low insulin responders« with normal or low glucose tolerance (N2). Among non-acromegalics expiration of 14CO2 was significantly lower in N2 than in N1. Among 4 non-acromegalic subjects treated with human growth hormone for 3–4 days one had a marked reduction in pyruvate oxidation, while all had a decrease in glucose tolerance. Analysis of 14C in blood glucose at 60 minutes after injection of [2-14C]pyruvate suggested that slightly more total 14C-glucose was present in A2 than N1 without any differences between A2 and N2 or N1 and N2. Two out of 4 studies in A1 showed lower than normal amounts of 14Cglucose. No change in 14C-glucose occurred after administration of HGH. The findings suggest that impairment of pyruvate oxidation accompanies a lowered glucose tolerance in acromegalics with a diabetic tendency. Changes in gluconeogenesis from pyruvate appear to be minimal.

scholarly journals Inhibition of oxidative metabolism by propionic acid and its reversal by carnitine in isolated rat hepatocytes

1986 ◽  
Vol 236 (1) ◽  
pp. 131-136 ◽  
Author(s):  
E P Brass ◽  
P V Fennessey ◽  
L V Miller
Keyword(s):  
Palmitic Acid ◽  
Propionic Acid ◽  
Oxidative Metabolism ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Acid Oxidation ◽  
Isolated Rat Hepatocytes ◽  
Pyruvate Oxidation ◽  
Metabolic Basis ◽  
Isolated Rat

The present study was designed to study the interaction of propionic acid and carnitine on oxidative metabolism by isolated rat hepatocytes. Propionic acid (10 mM) inhibited hepatocyte oxidation of [1-14C]-pyruvate (10 mM) by 60%. This inhibition was not the result of substrate competition, as butyric acid had minimal effects on pyruvate oxidation. Carnitine had a small inhibitory effect on pyruvate oxidation in the hepatocyte system (210 +/- 19 and 184 +/- 18 nmol of pyruvate/60 min per mg of protein in the absence and presence of 10 mM-carnitine respectively; means +/- S.E.M., n = 10). However, in the presence of propionic acid (10 mM), carnitine (10 mM) increased the rate of pyruvate oxidation by 19%. Under conditions where carnitine partially reversed the inhibitory effect of propionic acid on pyruvate oxidation, formation of propionylcarnitine was documented by using fast-atom-bombardment mass spectroscopy. Propionic acid also inhibited oxidation of [1-14C]palmitic acid (0.8 mM) by hepatocytes isolated from fed rats. The degree of inhibition caused by propionic acid was decreased in the presence of 10 mM-carnitine (41% inhibition in the absence of carnitine, 22% inhibition in the presence of carnitine). Propionic acid did not inhibit [1-14C]palmitic acid oxidation by hepatocytes isolated from 48 h-starved rats. These results demonstrate that propionic acid interferes with oxidative metabolism in intact hepatocytes. Carnitine partially reverses the inhibition of pyruvate and palmitic acid oxidation by propionic acid, and this reversal is associated with increased propionylcarnitine formation. The present study provides a metabolic basis for the efficacy of carnitine in patients with abnormal organic acid accumulation, and the observation that such patients appear to have increased carnitine requirements (‘carnitine insufficiency’).

Sign in / Sign up

Export Citation Format

Share Document