Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

1995 ◽  
Vol 269 (3) ◽  
pp. E458-E468 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
L. C. Lands ◽  
T. M. Bragg ◽  
M. G. Hollidge-Horvat ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Maximal Exercise ◽  
Vastus Lateralis ◽  
Active Form ◽  
Lactate Production ◽  
Glycolytic Flux ◽  
Muscle Lactate ◽  
Mitochondrial Oxidation ◽  
Exercise In Humans

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

Activation by Exercise of Human Skeletal Muscle Pyruvate Dehydrogenase In Vivo

1982 ◽  
Vol 63 (1) ◽  
pp. 87-92 ◽  
Author(s):  
G. R. Ward ◽  
J. R. Sutton ◽  
N. L. Jones ◽  
C. J. Toews
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Maximal Exercise ◽  
Intermittent Exercise ◽  
Vastus Lateralis ◽  
Active Form ◽  
Isometric Exercise ◽  
Vastus Lateralis Muscle ◽  
Glycogen Depletion ◽  
Muscle Lactate

1. The activity of pyruvate dehydrogenase in its active and inactive forms was measured in biopsy samples obtained from the vastus lateralis muscle of healthy subjects before and after exercise. 2. At rest, 40 ± 4% (mean ± sem) of the enzyme was in the active form. 3. After progressive aerobic exercise to exhaustion (n = 5), 88 ± 2·3% was in the active form. 4. After intermittent supramaximal short-term exercise (1 min exercise, 3 min rest) to exhaustion (n = 6), 60 ± 2·2% was in the active form. 5. After isometric maximal exercise of 65 ± 3·6 s duration (n = 3), only 39 ± 1% of the enzyme was in the active form. 6. Muscle glycogen depletion was greatest with intermittent exercise and least with isometric maximal exercise; in contrast, the increase in muscle lactate was least with progressive exercise (1·3 to 9·4 μmol/g), intermediate in intermittent maximal exercise (1·2 to 13·1 μmol/g) and greatest after isometric exercise (1·8 to 17·6 μmol/g). There were no significant differences between the three studies in the changes in lactate/pyruvate ratios. 7. In three subjects who exercised with one leg, activation of the enzyme was twice as great in the exercised as in the inactive leg. 8. The ratio of active to total enzyme in biopsies of resting muscle was greater in four well-trained athletes than in four untrained control subjects (70% compared with 41% respectively). 9. The activation of pyruvate dehydrogenase appears to play an important part in regulating the use of glycogen and glucose during exercise in man.

Enhanced pyruvate dehydrogenase activity does not affect muscle O2uptake at onset of intense exercise in humans

2002 ◽  
Vol 282 (1) ◽  
pp. R273-R280 ◽  
Author(s):  
Jens Bangsbo ◽  
Martin J. Gibala ◽  
Peter Krustrup ◽  
José González-Alonso ◽  
Bengt Saltin
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Initial Phase ◽  
Vastus Lateralis ◽  
Active Form ◽  
Lactate Production ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Experimental Conditions ◽  
Very High ◽  
Exercise In Humans

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDHa) and, subsequently, measured leg O2uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at ∼110% of thigh peak O2uptake (65.3 ± 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2uptake and lactate release. After DCA administration, PDHawas four- to eightfold higher ( P < 0.05) than Con at rest, and PDHaremained ∼130% and 100% higher ( P< 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDHabetween trials at rest and during the initial phase of exercise, thigh O2uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDHadoes not alter muscle O2uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.

Pyruvate dehydrogenase activation in inactive muscle during and after maximal exercise in men

1999 ◽  
Vol 276 (3) ◽  
pp. E483-E488 ◽  
Author(s):  
C. T. Putman ◽  
M. P. Matsos ◽  
E. Hultman ◽  
N. L. Jones ◽  
G. J. F. Heigenhauser
Keyword(s):  
Skeletal Muscle ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Maximal Exercise ◽  
Exercise Bout ◽  
Deltoid Muscle ◽  
Muscle Lactate ◽  
Leg Exercise ◽  
Acetyl Group

Pyruvate dehydrogenase activity (PDHa) and acetyl-group accumulation were examined in the inactive deltoid muscle in response to maximal leg exercise in men. Seven subjects completed three consecutive 30-s bouts of maximal isokinetic cycling, with 4-min rest intervals between bouts. Biopsies of the deltoid were obtained before exercise, after bouts 1 and 3, and after 15 min of rest recovery. Inactive muscle lactate (LA) and pyruvate (PYR) contents increased more than twofold ( P < 0.05) after exercise ( bout 3) and remained elevated after 15 min of recovery ( P < 0.05). Increased PYR accumulation secondary to LA uptake by the inactive deltoid was associated with greater PDHa, which progressively increased from 0.71 ± 0.23 mmol ⋅ min−1 ⋅ kg wet wt−1 at rest to a maximum of 1.83 ± 0.30 mmol ⋅ min−1 ⋅ kg wet wt−1 after bout 3( P < 0.05) and remained elevated after 15 min of recovery (1.63 ± 0.24 mmol ⋅ min−1 ⋅ kg wet wt−1; P < 0.05). Acetyl-CoA and acetylcarnitine accumulations were unaltered. Increased PDHa allowed and did not limit the oxidation of LA and PYR in inactive human skeletal muscle after maximal exercise.

Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet

1998 ◽  
Vol 275 (6) ◽  
pp. E980-E986 ◽  
Author(s):  
Sandra J. Peters ◽  
Timothy A. St. Amand ◽  
Richard A. Howlett ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Active Form ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). β-Hydroxyacyl CoA dehydrogenase, active PDH (PDHa), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 ± 0.02 min−1 to 0.35 ± 0.09 min−1 at 3 days and 0.49 ± 0.06 min−1 after 6 days. Resting PDHa activity decreased from 0.63 ± 0.17 to 0.17 ± 0.04 mmol ⋅ min−1 ⋅ kg−1after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.

Glycogen phosphorylase and pyruvate dehydrogenase transformation in white muscle of trout during high-intensity exercise

2002 ◽  
Vol 282 (3) ◽  
pp. R828-R836 ◽  
Author(s):  
Jeff G. Richards ◽  
George J. F. Heigenhauser ◽  
Chris M. Wood
Keyword(s):  
Pyruvate Dehydrogenase ◽  
High Intensity ◽  
Glycogen Phosphorylase ◽  
Time Course ◽  
White Muscle ◽  
Active Form ◽  
Lactate Production ◽  
High Intensity Exercise ◽  
Glycolytic Flux ◽  
Atp Turnover

We examined the regulation of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in white muscle of rainbow trout during a continuous bout of high-intensity exercise that led to exhaustion in 52 s. The first 10 s of exercise were supported by creatine phosphate hydrolysis and glycolytic flux from an elevated glycogenolytic flux and yielded a total ATP turnover of 3.7 μmol · g wet tissue−1 · s−1. The high glycolytic flux was achieved by a large transformation of Phos into its active form. Exercise performed from 10 s to exhaustion was at a lower ATP turnover rate (0.5 to 1.2 μmol · g wet tissue−1 · s−1) and therefore at a lower power output. The lower ATP turnover was supported primarily by glycolysis and was reduced because of posttransformational inhibition of Phos by glucose 6-phosphate accumulation. During exercise, there was a gradual activation of PDH, which was fully transformed into its active form by 30 s of exercise. Oxidative phosphorylation, from PDH activation, only contributed 2% to the total ATP turnover, and there was no significant activation of lipid oxidation. The time course of PDH activation was closely associated with an increase in estimated mitochondrial redox (NAD+-to-NADH concentration ratio), suggesting that O2 was not limiting during high-intensity exercise. Thus anaerobiosis may not be responsible for lactate production in trout white muscle during high-intensity exercise.

Effects of short-term submaximal training in humans on muscle metabolism in exercise

1998 ◽  
Vol 275 (1) ◽  
pp. E132-E139 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
E. Hultman ◽  
M. G. Hollidge-Horvat ◽  
A. Bonen ◽  
...  
Keyword(s):  
Steady State ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Femoral Vein ◽  
Active Form ◽  
Lactate Production ◽  
Muscle Metabolism ◽  
Cycle Ergometer ◽  
Muscle Lactate ◽  
Before And After

Muscle metabolism, including the role of pyruvate dehydrogenase (PDH) in muscle lactate (Lac−) production, was examined during incremental exercise before and after 7 days of submaximal training on a cycle ergometer [2 h daily at 60% peak O2 uptake (V˙o 2 max)]. Subjects were studied at rest and during continuous steady-state cycling at three stages (15 min each): 30, 65, and 75% of the pretraining V˙o 2 max. Blood was sampled from brachial artery and femoral vein, and leg blood flow was measured by thermodilution. Biopsies of the vastus lateralis were obtained at rest and during steady-state exercise at the end of each stage. V˙o 2 max, leg O2 uptake, and the maximum activities of citrate synthase and PDH were not altered by training; muscle glycogen concentration was higher. During rest and cycling at 30% V˙o 2 max, muscle Lac− concentration ([Lac−]) and leg efflux were similar. At 65%V˙o 2 max, muscle [Lac−] was lower (11.9 ± 3.2 vs. 20.0 ± 5.8 mmol/kg dry wt) and Lac− efflux was less [−0.22 ± 0.24 (one leg) vs. 1.42 ± 0.33 mmol/min] after training. Similarly, at 75%V˙o 2 max, lower muscle [Lac−] (17.2 ± 4.4 vs. 45.2 ± 6.6 mmol/kg dry wt) accompanied less release (0.41 ± 0.53 vs. 1.32 ± 0.65 mmol/min) after training. PDH in its active form (PDHa) was not different between conditions. Calculated pyruvate production at 75%V˙o 2 max fell by 33%, pyruvate reduction to lactate fell by 59%, and pyruvate oxidation fell by 24% compared with before training. Muscle contents of coenzyme A and phosphocreatine were higher during exercise after training. Lower muscle lactate production after training resulted from improved matching of glycolytic and PDHafluxes, independently of changes in muscle O2 consumption, and was associated with greater phosphorylation potential.

Changes in Plasma Electrolytes and Muscle Substrates During Short-Term Maximal Exercise in Humans

1995 ◽  
Vol 20 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Marcel R. Boulay ◽  
Olivier Serresse ◽  
Germain Thériault ◽  
Jean-Aimé Simoneau ◽  
Claude Bouchard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Maximal Exercise ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Exercise Duration ◽  
Hydration Status ◽  
Short Term ◽  
Exercise Tests ◽  
Muscle Lactate ◽  
Plasma Electrolytes

This study compared the effects of 3 short-term maximal exercise tests lasting 10, 30, and 90 sec upon blood volume, plasma electrolytes, glucose, glycerol, lactate and skeletal muscle ATP, PC, glycogen, and lactate concentrations. Seven sedentary male subjects were recruited and 5 of them were randomly assigned to each of the 3 protocols. The tests were performed on a modified ergocycle at workloads of 0.9, 0.075, and 0.05 kp∙kg−1 body mass, respectively. Muscle biopsies were taken from the vastus lateralis before and immediately after each exercise. Venous blood samples were collected before, immediately after, and during the recovery (5, 20, 60, and 120 min). Plasma volume decreased during the 30- and 90-sec tests and was increased in all tests after 60 min of recovery. Plasma K+ increased during all tests and returned to normal values 5 min postexercise, except after the 90-sec test where it fell below resting values. Plasma Na+ and Cl− were unaffected. Blood lactate increased in all tests, glucose increased after the 90-sec test, and glycerol increased after the 30- and 90-sec tests. All 3 tests brought relatively similar changes in muscle ATP, PC, and glycogen while muscle lactate changes were related to exercise duration. These results suggest that a normal hydration status is important for a subject undergoing short training bouts, and that high-intensity tests of short duration do not require a special nutritional regimen to enhance glycogen reserves. Key words: skeletal muscle, hemoconcentration, hypervolemia, hyperkalemia

scholarly journals Carbohydrate ingestion does not alter skeletal muscle AMPK signaling during exercise in humans

2006 ◽  
Vol 291 (3) ◽  
pp. E566-E573 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Matthew J. Palmer ◽  
Kelly C. Linden ◽  
Kieran LePlastrier ◽  
Benedict J. Canny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Glucose ◽  
Plasma Epinephrine ◽  
Muscle Lactate ◽  
Carbohydrate Ingestion ◽  
Ampk Signaling ◽  
Glucose Levels ◽  
Exercise Induced ◽  
Exercise In Humans

There is evidence that increasing carbohydrate (CHO) availability during exercise by raising preexercise muscle glycogen levels attenuates the activation of AMPKα2 during exercise in humans. Similarly, increasing glucose levels decreases AMPKα2 activity in rat skeletal muscle in vitro. We examined the effect of CHO ingestion on skeletal muscle AMPK signaling during exercise in nine active male subjects who completed two 120-min bouts of cycling exercise at 65 ± 1% V̇o2 peak. In a randomized, counterbalanced order, subjects ingested either an 8% CHO solution or a placebo solution during exercise. Compared with the placebo trial, CHO ingestion significantly ( P < 0.05) increased plasma glucose levels and tracer-determined glucose disappearance. Exercise-induced increases in muscle-calculated free AMP (17.7- vs. 11.8-fold), muscle lactate (3.3- vs. 1.8-fold), and plasma epinephrine were reduced by CHO ingestion. However, the exercise-induced increases in skeletal muscle AMPKα2 activity, AMPKα2 Thr172 phosphorylation and acetyl-CoA Ser222 phosphorylation, were essentially identical in the two trials. These findings indicate that AMPK activation in skeletal muscle during exercise in humans is not sensitive to changes in plasma glucose levels in the normal range. Furthermore, the rise in plasma epinephrine levels in response to exercise was greatly suppressed by CHO ingestion without altering AMPK signaling, raising the possibility that epinephrine does not directly control AMPK activity during muscle contraction under these conditions in vivo.

Poor relationship between arterial [lactate] and leg net release during exercise at 4,300 m altitude

1998 ◽  
Vol 275 (4) ◽  
pp. R1192-R1201 ◽  
Author(s):  
George A. Brooks ◽  
Eugene E. Wolfel ◽  
Gail E. Butterfield ◽  
Allen Cymerman ◽  
Amy C. Roberts ◽  
...  
Keyword(s):  
Vastus Lateralis ◽  
Venous Blood ◽  
Lactate Production ◽  
Acute Exposure ◽  
Muscle Lactate ◽  
Arterial Lactate ◽  
Arterial Concentration ◽  
Exercise Onset ◽  
Intermediate Response ◽  
Net Release

We evaluated the hypotheses that on acute exposure to hypobaric hypoxia, sympathetic stimulation leads to augmented muscle lactate production and circulating [lactate] through a β-adrenergic mechanism and that β-adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise lactate response after acclimatization to altitude. Five control and 6 β-blocked men were studied during rest and exercise at sea level (SL), on acute exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was by leg cycling at 49% of SL peak O2 consumption (V˙o 2 peak) (65% of altitude V˙o 2 peak or 87 ± 2.6 W); β-blockade was by propranolol (80 mg 3× daily), femoral arterial and venous blood was sampled; leg blood flow (Q˙) was measured by thermodilution, leg lactate net release [L˙ = (2) (1-leg Q) venous-arterial concentrationL] was calculated, and vastus lateralis needle biopsies were obtained. Muscle [lactate] increased with exercise and acute altitude exposure but regressed to SL values with acclimatization; β-blockade had no effect on muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 ± 0.1 to 1.5 ± 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 ± 0.8 mM), and exercise at A2 an intermediate response (2.1 ± 0.6 mM). β-Blockade reduced circulating [lactate] ∼45% during exercise under all altitude conditions. L˙ increased transiently at exercise onset but then declined over time under all conditions. Blood and muscle “lactate paradoxes” occurred independent of β-adrenergic influences, and the hypotheses relating the blood lactate response at altitude to β-adrenergic mechanisms are rejected. During exercise at altitude, arterial [lactate] is determined by factors in addition to hypoxemia, circulating epinephrine, and net lactate release from active muscle beds.

Phosphorylase a in human skeletal muscle during exercise and electrical stimulation

1978 ◽  
Vol 45 (6) ◽  
pp. 852-857 ◽  
Author(s):  
P. D. Gollnick ◽  
J. Karlsson ◽  
K. Piehl ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Muscular Activity ◽  
Voluntary Exercise ◽  
Vastus Lateralis Muscle ◽  
Minor Importance ◽  
Muscle Lactate ◽  
Needle Technique

Experiments were conducted to examine the conversions of phosphorylase b to phosphorylase a in human skeletal muscle during bicycle exercise or isometric contractions. Muscle biopsies were obtained from the vastus lateralis with the needle technique at rest and either during or immediately after activity and frozen in liquid nitrogen within 2--4 s. Total phosphorylase and phosphorylase a activities were differentiated by measurement in the presence and absence of AMP, respectively. At rest 8.5% of the total phosphorylase activity existed in the a form. Little or no change in the percent of phosphorylase in the a form occurred during voluntary dynamic or static muscular activity that produced muscle lactate concentrations in excess of 18 mmol.kg-1 wet muscle. Electrical stimulation of the vastus lateralis muscle also failed to produce an increase in the percentage of phosphorylase a. These data suggest that during exercise the conversion of phosphorylase to the a form is of minor importance. An increased activity of phosphorylase b due to changes in muscle concentrations of ATP, AMP, and inorganic phosphate may regulate glycogenolysis during voluntary exercise in man.

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