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.

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.

scholarly journals Effect of high-intensity intermittent training on lactate and H+ release from human skeletal muscle

2004 ◽  
Vol 286 (2) ◽  
pp. E245-E251 ◽  
Author(s):  
Carsten Juel ◽  
Christina Klarskov ◽  
Jens Jung Nielsen ◽  
Peter Krustrup ◽  
Magni Mohr ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Venous Blood ◽  
Knee Extensor ◽  
Exercise Bout ◽  
Test Time ◽  
Incremental Test ◽  
Muscle Lactate ◽  
Lactate Release

The study investigated the effect of training on lactate and H+ release from human skeletal muscle during one-legged knee-extensor exercise. Six subjects were tested after 7–8 wk of training (fifteen 1-min bouts at ∼150% of thigh maximal O2 uptake per day). Blood samples, blood flow, and muscle biopsies were obtained during and after a 30-W exercise bout and an incremental test to exhaustion of both trained (T) and untrained (UT) legs. Blood flow was 16% higher in the T than in the UT leg. In the 30-W test, venous lactate and lactate release were lower in the T compared with the UT leg. In the incremental test, time to fatigue was 10.6 ± 0.7 and 8.2 ± 0.7 min, respectively, in the T and UT legs ( P < 0.05). At exhaustion, venous blood lactate was 10.7 ± 0.4 and 8.0 ± 0.9 mmol/l in T and UT legs ( P < 0.05), respectively, and lactate release was 19.4 ± 3.6 and 10.6 ± 2.0 mmol/min ( P < 0.05). H+ release at exhaustion was higher in the T than in the UT leg. Muscle lactate content was 59.0 ± 15.1 and 96.5 ± 14.5 mmol/kg dry wt in the T and UT legs, and muscle pH was 6.82 ± 0.05 and 6.69 ± 0.04 in the T and UT legs ( P = 0.06). The membrane contents of the monocarboxylate transporters MCT1 and MCT4 and the Na+/H+ exchanger were 115 ± 5 ( P < 0.05), 111 ± 11, and 116 ± 6% ( P < 0.05), respectively, in the T compared with the UT leg. The reason for the training-induced increase in peak lactate and H+ release during exercise is a combination of an increased density of the lactate and H+ transporting systems, an improved blood flow and blood flow distribution, and an increased systemic lactate and H+ clearance.

Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans

1995 ◽  
Vol 268 (5) ◽  
pp. E1007-E1017 ◽  
Author(s):  
C. T. Putman ◽  
L. L. Spriet ◽  
E. Hultman ◽  
D. J. Dyck ◽  
G. J. Heigenhauser
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Acetate Metabolism ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
Citrate Accumulation ◽  
Acetyl Group ◽  
Glucose Fatty Acid Cycle

Pyruvate dehydrogenase activity (PDHa), acetyl group, and citrate accumulation were examined in human skeletal muscle at rest and during cycling exercise while acetate was infused. Eight subjects received 400 mmol of sodium acetate (Ace) at a constant rate during 20 min of rest, 5 min of cycling at 40% maximal O2 uptake (VO2max) and 15 min of cycling at 80% VO2max. Two weeks later experiments were repeated while 400 mmol of sodium bicarbonate was infused in the control condition (CON). Ace infusion increased muscle acetyl-coenzyme A (acetyl-CoA), citrate, and acetylcarnitine. A decline in resting PDHa during 20 min of Ace infusion (0.37 +/- 0.08 vs. 0.16 +/- 0.03 mmol.min-1.kg wet wt-1) coincided with an elevation in the acetyl-CoA-to-free CoA ratio (acetyl-CoA/CoASH; 0.28 +/- 0.04 to 0.73 +/- 0.14). After 20 min of CON infusion, resting PDHa (0.32 +/- 0.06 mmol.min-1.kg wet wt-1) was similar to PDHa before Ace infusion. During exercise, acetyl-CoA, citrate, and acetyl-CoA/CoASH were further elevated, and the differences that existed at rest were resolved. PDHa increased to the same extent in Ace and CON, in which it was 44-47% transformed after 5 min at 40% VO2max and completely transformed after 15 min at 80% VO2max. At rest PDHa was regulated by variations in acetyl-CoA/CoASH secondary to enhanced acetate metabolism. Conversely, during exercise PDHa regulation appeared independent of variations in acetyl-CoA/CoASH. The resting data are consistent with a central role for PDHa and citrate in the regulation of the glucose-fatty acid cycle in skeletal muscle, as classically proposed. However, in the present study Ace infusion was not effective in perturbing the glucose-fatty acid cycle during exercise.

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity

2011 ◽  
Vol 111 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Lorenzo K. Love ◽  
Paul J. LeBlanc ◽  
J. Greig Inglis ◽  
Nicolette S. Bradley ◽  
Jon Choptiany ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Endurance Training ◽  
Aerobic Capacity ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Carbohydrate Oxidation ◽  
Pyruvate Dehydrogenase Phosphatase

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity ( r2 = 0.399, P = 0.001) and PDP1 protein expression ( r2 = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α ( r2 = 0.310, P = 0.002) and PDK2 protein ( r2 = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼18% of the variance in PDP activity ( r2 = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼38% of the variance in PDP activity ( r2 = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).

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.

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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