Hyperammoniemia during prolonged exercise: an effect of glycogen depletion?

Eight healthy men exercised to exhaustion on a cycle ergometer at a work load of 176 +/- 9 (SE) W corresponding to 67% (range 63-69%) of their maximal O2 uptake (exercise I). Exercise of the same work load was repeated after 75 min of recovery (exercise II). Exercise duration (range) was 65 (50-90) and 21 (14-30) min for exercise I and II, respectively. Femoral venous blood samples were obtained before and during exercise and analyzed for NH3 and lactate. Plasma NH3 was 12 +/- 2 and 19 +/- 6 mumol/l before exercise I and II, respectively and increased during exercise to exhaustion to peak values of 195 +/- 29 (exercise I) and 250 +/- 30 (exercise II) mumol/l, respectively. Plasma NH3 increased faster during exercise II compared with exercise I and at the end of exercise II was threefold higher than the value for the corresponding time of exercise I (P less than 0.001). Blood lactate increased during exercise I and after 20 min of exercise was 3.7 +/- 0.4 mmol/l and remained unchanged until exhaustion. During exercise II blood lactate increased less than during exercise I. It is concluded that long-term exercise to exhaustion results in large increases in plasma NH3 despite relatively low levels of blood lactate. It is suggested that the faster increase in plasma NH3 during exercise II (vs. exercise I) reflects an increased formation in the working muscle that may be caused by low glycogen levels and impairment of the ATP resynthesis.     

Skeletal muscle energy metabolism during prolonged, fatiguing exercise.

A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5'-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O(2) uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R295-R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 +/- 3% of LT ( approximately 65% peak O(2) uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, approximately 40 min before fatigue (F-40 =143 +/- 13 min), and at fatigue (F = 186 +/- 31 min). Glycogen concentration progressively declined (P < 0.01) to very low levels at fatigue (28 +/- 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F-40 was compared with F and was only reduced by 40% when F was compared with rest (52. 8 +/- 3.7 vs. 87.8 +/- 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation (r = 0.95; P < 0. 05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.     

Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise.

The hypothesis that fatigue during prolonged exercise arises from insufficient intramuscular glycogen, which limits tricarboxylic acid cycle (TCA) activity due to reduced TCA cycle intermediates (TCAI), was tested in this experiment. Seven endurance-trained men cycled at approximately 70% of peak O(2) uptake (Vo(2 peak)) until exhaustion with low (LG) or high (HG) preexercise intramuscular glycogen content. Muscle glycogen content was lower (P < 0.05) at fatigue than at rest in both trials. However, the increase in the sum of four measured TCAI (>70% of the total TCAI pool) from rest to 15 min of exercise was not different between trials, and TCAI content was similar after 103 +/- 15 min of exercise (2.62 +/- 0.31 and 2.59 +/- 0.28 mmol/kg dry wt for LG and HG, respectively), which was the point of volitional fatigue during LG. Subjects cycled for an additional 52 +/- 9 min during HG, and although glycogen was markedly reduced (P < 0.05) during this period, no further change in the TCAI pool was observed, thus demonstrating a clear dissociation between exercise duration and the size of the TCAI pool. Neither the total adenine nucleotide pool (TAN = ATP + ADP + AMP) nor IMP was altered compared with rest in either trial, whereas creatine phosphate levels were not different when values measured at fatigue were compared with those measured after 15 min of exercise. These data demonstrate that altered glycogen availability neither compromises TCAI pool expansion nor affects the TAN pool or creatine phosphate or IMP content during prolonged exercise to fatigue. Therefore, our data do not support the concept that a decrease in muscle TCAI during prolonged exercise in humans compromises aerobic energy provision or is the cause of fatigue.     

Propranolol enhances adenine nucleotide degradation in human muscle during exercise

Eight healthy men cycled to exhaustion [4.1 +/- 0.3 (SE) min] during beta-adrenoceptor blockade (beta B) with propranolol. The exercise was repeated on another day with the same power output and duration but without propranolol (control). The total adenine nucleotide (TAN) content in muscle (quadriceps femoris) decreased during exercise, and the decrease was more pronounced during beta B (delta TAN = 4.8 +/- 1.0 mmol/kg dry wt) than during control (delta TAN = 2.8 +/- 0.9; P less than 0.01, beta B vs. control). The decrease in TAN corresponded with a similar increase in inosine 5'-monophosphate (IMP). The increase in IMP was more pronounced during beta B (delta IMP = 5.1 +/- 1.2 mmol/kg dry wt) than during control (delta IMP = 2.8 +/- 0.7; P less than 0.05, beta B vs. control). Similarly, the increase in the content of NH3 in muscle was twice as high during beta B vs. control (P less than 0.01). The increase in muscle lactate and the decrease in phosphocreatine during exercise were similar between treatments, but postexercise hexose phosphates were approximately twofold higher (P less than 0.05) during control than during beta B. It is concluded that beta B enhances the degradation of TAN and the production of NH3 and IMP in muscle during intense exercise. This indicates that the imbalance between the rates of utilization and resynthesis of ATP is more pronounced during beta B possibly because of a decreased O2 transport to the contracting muscle and a diminished activation of glycolysis by the hexose phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise.

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.     

Plasma hypoxanthine and ammonia in humans during prolonged exercise

In this study we examined the time course of changes in the plasma concentration of oxypurines [hypoxanthine (Hx), xanthine and urate] during prolonged cycling to fatigue. Ten subjects with an estimated maximum oxygen uptake (VO2(max)) of 54 (range 47-67) ml x kg(-1) x min(-1) cycled at [mean (SEM)] 74 (2)% of VO2(max) until fatigue [79 (8) min]. Plasma levels of oxypurines increased during exercise, but the magnitude and the time course varied considerably between subjects. The plasma concentration of Hx ([Hx]) was 1.3 (0.3) micromol/l at rest and increased eight fold at fatigue. After 60 min of exercise plasma [Hx] was >10 micromol/l in four subjects, whereas in the remaining five subjects it was <5 micromol/l. The muscle contents of total adenine nucleotides (TAN = ATP+ADP+AMP) and inosine monophosphate (IMP) were measured before and after exercise in five subjects. Subjects with a high plasma [Hx] at fatigue also demonstrated a pronounced decrease in muscle TAN and increase in IMP. Plasma [Hx] after 60 min of exercise correlated significantly with plasma concentration of ammonia ([NH(3)], r = 0.90) and blood lactate (r = 0.66). Endurance, measured as time to fatigue, was inversely correlated to plasma [Hx] at 60 min (r = -0.68, P < 0.05) but not to either plasma [NH(3)] or blood lactate. It is concluded that during moderate-intensity exercise, plasma [Hx] increases, but to a variable extent between subjects. The present data suggest that plasma [Hx] is a marker of adenine nucleotide degradation and energetic stress during exercise. The potential use of plasma [Hx] to assess training status and to identify overtraining deserves further attention.     

Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans.

The relationship between changes in the muscle total adenine nucleotide pool (TAN = ATP + ADP + AMP) and IMP during and after 30 s of sprint cycling was examined. Skeletal muscle samples were obtained from the vastus lateralis muscle of seven untrained men (23. 9 +/- 2.3 yr, 74.4 +/- 3.6 kg, and 55.0 +/- 2.9 ml. kg(-1). min(-1) peak oxygen consumption) before and immediately after exercise and after 5 and 10 min of passive recovery. The exercise-induced increase in muscle IMP was linearly related to the decrease in muscle TAN (r = -0.97, P < 0.01), and the slope of this relationship (-0.83) was not different from 1.0 (P > 0.05), indicating a 1:1 stoichiometric relationship. This interpretation must be treated cautiously, because all subjects displayed a greater decrease in TAN compared with the increase in IMP content, and the TAN + IMP + inosine + hypoxanthine content was lower (P < 0.05) immediately after exercise compared with during rest. During the first 5 min of recovery, the increase in TAN was not correlated with the decrease in IMP (r = -0.18, P > 0.05). In all subjects, the magnitude of TAN increase was higher than the magnitude of IMP decrease over this recovery period. In contrast, the increase in TAN was correlated with the decrease in IMP throughout the second 5 min of recovery (r = -0.80, P < 0.05), and it was a 1:1 stoichiometric relationship (slope = -1.12). These data indicate that a small proportion of the TAN pool was temporarily lost from the muscle purine stores during sprinting but was rapidly recovered after exercise.     

Adenosine nucleotide utilization in subtotally nephrectomized rabbits

Two- to three-kilogram albino rabbits were subtotally nephrectomized and compared with sham-operated normal rabbits for the muscle content of adenosine mono (AMP)-, di (ADP)- and triphosphate (ATP) and inosine monophosphate (IMP) before and after exercise. Analysis of snap-frozen, lyophilized soleus muscle showed lower levels of AMP, ATP and total adenosine nucleotide (TAN) (p less than 0.01) and ATP/ADP (p less than 0.02) in the subtotally nephrectomized animals. IMP levels following exercise were higher in the experimental animals. Muscle adenosine nucleotide concentrations in the experimental animals were significantly different for normals, thus suggesting that minimal azotemia could adversely affect muscle function in these animals.     

Abnormal high-energy phosphate metabolism in human muscle phosphofructokinase deficiency.

We studied the pattern of high-energy phosphate metabolism in five patients with phosphofructokinase deficiency (PFKD) and five healthy subjects (HS) during graded rhythmic handgrip performed for 5 min at 17, 33, 50, and 100% of maximal voluntary contraction (MVC). The range of MVC was similar in both groups. Force production was recorded, and intracellular concentrations of phosphorus compounds and pH were measured in the flexor digitorum profundus of the active forearm. At exercise intensities greater than or equal to 50% MVC, changes in concentrations of high-energy phosphate metabolites were abnormal in PFKD. During maximal effort, [ADP], calculated from the creatine kinase reaction, was 64.3 +/- 13.5 (SE) mumol/kg in PFKD vs. 25.7 +/- 4.0 in HS (P less than 0.05). Ammonia (NH3), a product of AMP deamination and an index of muscle [AMP], increased approximately twofold more in venous effluent during maximal forearm exercise in PFKD than in HS (P less than 0.05). Phosphocreatine concentration was 9.4 +/- 1.3 (SE) mmol/kg in HS and 13.0 +/- 1.7 in PFKD (P less than 0.05). Inorganic phosphate concentration was 15.8 +/- 1.4 mmol/kg in HS and 7.4 +/- 0.5 in PFKD (P less than 0.05). During strenuous exercise, PFKD patients exhibit an impairment in the rephosphorylation of ADP related to a subnormal oxidative capacity, an absence of glycolysis, and an attenuated breakdown of phosphocreatine.     

Effect of epinephrine on glucose disposal during exercise in humans: role of muscle glycogen

This study examined the effect of epinephrine on glucose disposal during moderate exercise when glycogenolytic flux was limited by low preexercise skeletal muscle glycogen availability. Six male subjects cycled for 40 min at 59 +/- 1% peak pulmonary O2 uptake on two occasions, either without (CON) or with (EPI) epinephrine infusion starting after 20 min of exercise. On the day before each experimental trial, subjects completed fatiguing exercise and then maintained a low carbohydrate diet to lower muscle glycogen. Muscle samples were obtained after 20 and 40 min of exercise, and glucose kinetics were measured using [6,6-2H]glucose. Exercise increased plasma epinephrine above resting concentrations in both trials, and plasma epinephrine was higher (P < 0.05) during the final 20 min in EPI compared with CON. Muscle glycogen levels were low after 20 min of exercise (CON, 117 +/- 25; EPI, 122 +/- 20 mmol/kg dry matter), and net muscle glycogen breakdown and muscle glucose 6-phosphate levels during the subsequent 20 min of exercise were unaffected by epinephrine infusion. Plasma glucose increased with epinephrine infusion (i.e., 20-40 min), and this was due to a decrease in glucose disposal (R(d)) (40 min: CON, 33.8 +/- 3; EPI, 20.9 +/- 4.9 micromol. kg(-1). min(-1), P < 0.05), because the exercise-induced rise in glucose rate of appearance was similar in the trials. These results show that glucose R(d) during exercise is reduced by elevated plasma epinephrine, even when muscle glycogen availability and utilization are low. This suggests that the effect of epinephrine does not appear to be mediated by increased glucose 6-phosphate, secondary to enhanced muscle glycogenolysis, but may be linked to a direct effect of epinephrine on sarcolemmal glucose transport.     

HSP72 gene expression progressively increases in human skeletal muscle during prolonged, exhaustive exercise.

To examine the effect of exercise on heat shock protein (HSP) 72 mRNA expression in skeletal muscle, five healthy humans (20 +/- 1 yr; 64 +/- 3 kg; peak O(2) uptake of 2.55 +/- 0.2 l/min) cycled until exhaustion at a workload corresponding to 63% peak O(2) uptake. Muscle was sampled from the vastus lateralis, and muscle temperature was measured at rest (R), 10 min of exercise (Min10), approximately 40 min before fatigue (F-40 = 144 +/- 7 min), and fatigue (F = 186 +/- 15 min). Muscle samples were analyzed for HSP72 mRNA expression, as well as glycogen and lactate concentration. Muscle temperature increased (P < 0.05) during the first 10 min of exercise but then remained constant for the duration of the exercise. Similarly, lactate concentration increased (P < 0.05) when Min10 was compared with R but decreased (P < 0.05) thereafter, such that concentrations at F-40 and F were not different from those at R. In contrast, muscle glycogen concentration fell progressively throughout exercise (486 +/- 74 vs. 25 +/- 7 mmol/kg dry weight for R and F, respectively; P < 0.05). HSP72 mRNA was detected at R but did not increase by Min10. However, HSP72 mRNA increased (P < 0.05) 2.2 +/- 0.5- and 2.6 +/- 0.9-fold, respectively, when F-40 and F were compared with R. These data demonstrate that HSP72 mRNA increases progressively during acute cycling, suggesting that processes that take place throughout concentric exercise are capable of initiating a stress response.     

Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability.

Eight endurance-trained men cycled to volitional exhaustion at 69 +/- 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies (n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by approximately 30% when carbohydrate was ingested [199 +/- 21 vs. 152 +/- 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 +/- 0.08, Con: 0.23 +/- 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.     

Muscle power and metabolism in maximal intermittent exercise

Muscle power and the associated metabolic changes in muscle were investigated in eight male human subjects who performed four 30-s bouts of maximal isokinetic cycling at 100 rpm, with 4-min recovery intervals. In the first bout peak power and total work were (mean +/- SE) 1,626 +/- 102 W and 20.83 +/- 1.18 kJ, respectively; muscle glycogen decreased by 18.2 mmol/kg wet wt, lactate increased to 28.9 +/- 2.7 mmol/kg, and there were up to 10-fold increases in glycolytic intermediates. External power and work decreased by 20% in both the second and third exercise periods, but no further change occurred in the fourth bout. Muscle glycogen decreased by an additional 14.8 mmol/kg after the second exercise and thereafter remained constant. Muscle adenosine triphosphate (ATP) was reduced by 40% from resting after each exercise period; creatine phosphate (CP) decreased successively to less than 5% of resting; in the recovery periods ATP and CP increased to 76 and 95% of initial resting levels, respectively. Venous plasma glycerol increased linearly to 485% of resting; free fatty acids did not change. Changes in muscle glycogen, lactate, and glycolytic intermediates suggested rate limitation at phosphofructokinase during the first and second exercise periods, and phosphorylase in the third and fourth exercise periods. Despite minimal glycolytic flux in the third and fourth exercise periods, subjects generated 1,000 W peak power and sustained 400 W for 30 s, 60% of the values recorded in the first exercise period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of endurance exercise training on muscle glycogen accumulation in humans.

The purpose of this investigation was to determine whether endurance exercise training increases the ability of human skeletal muscle to accumulate glycogen after exercise. Subjects (4 women and 2 men, 31 +/- 8 yr old) performed high-intensity stationary cycling 3 days/wk and continuous running 3 days/wk for 10 wk. Muscle glycogen concentration was measured after a glycogen-depleting exercise bout before and after endurance training. Muscle glycogen accumulation rate from 15 min to 6 h after exercise was twofold higher (P < 0.05) in the trained than in the untrained state: 10.5 +/- 0.2 and 4.5 +/- 1.3 mmol. kg wet wt(-1). h(-1), respectively. Muscle glycogen concentration was higher (P < 0.05) in the trained than in the untrained state at 15 min, 6 h, and 48 h after exercise. Muscle GLUT-4 content after exercise was twofold higher (P < 0.05) in the trained than in the untrained state (10.7 +/- 1.2 and 4.7 +/- 0.7 optical density units, respectively) and was correlated with muscle glycogen concentration 6 h after exercise (r = 0.64, P < 0.05). Total glycogen synthase activity and the percentage of glycogen synthase I were not significantly different before and after training at 15 min, 6 h, and 48 h after exercise. We conclude that endurance exercise training enhances the capacity of human skeletal muscle to accumulate glycogen after glycogen-depleting exercise.     

Metabolic response to maximal exercise of 800 and 2,000 m in the thoroughbred horse

To define the metabolic response to maximal exercise in the thoroughbred horse under field conditions, muscle biopsies and venous blood samples were taken from five horses after a single 800-m gallop and from four horses after a single 2,000-m gallop. Muscle and blood samples were also collected during 60 min of recovery. After exercise muscle ATP contents were decreased by 30 +/- 7 (SD) and 47 +/- 3% after the 800- and 2,000-m gallops, respectively. As indicators of purine catabolism, ammonia and uric acid increased in plasma, the accumulation being greater after the 2,000-m gallop. Blood ammonia peaked immediately after exercise and uric acid after 40-60 min of recovery. Muscle glycogen utilization over the 800- and 2,000-m gallops averaged 2.68 +/- 0.90 and 1.06 +/- 0.12 mmol glucosyl units.kg dry muscle-1.s-1, respectively, and the total used amounted to 27.3 +/- 6.6 and 32.5 +/- 8.8% of the initial store. Muscle lactate accumulation averaged 123.5 +/- 49.7 and 167.3 +/- 20.7 mmol/kg dry muscle, respectively, and declined during recovery with half times of 22.9 +/- 4.2 and 18.9 +/- 6.6 min. Blood lactate peaked 5-10 min after exercise. Exercise resulted in only a small increase in muscle glycerol content, but this continued to rise during recovery reaching 9-12 mmol/kg dry muscle after 20 min. During this time the increase in muscle glycerol content exactly matched the decline in glycerol 3-phosphate.     

Glucose formation in human skeletal muscle. Influence of glycogen content.

Eight men exercised at 66% of their maximal isometric force to fatigue after prior decrease in the glycogen store in one leg (low-glycogen, LG). The exercise was repeated with the contralateral leg (control) at the same relative intensity and for the same duration. Muscle (quadriceps femoris) glycogen content decreased in the LG leg from 199 +/- 17 (mean +/- S.E.M.) to 163 +/- 16 mmol of glucosyl units/kg dry wt. (P less than 0.05), and in the control leg from 311 +/- 23 to 270 +/- 18 mmol/kg (P less than 0.05). The decrease in glycogen corresponded to a similar accumulation of glycolytic intermediates. Muscle glucose increased in the LG leg during the contraction, from 1.8 +/- 0.1 to 4.3 +/- 0.6 mmol/kg dry wt. (P less than 0.01), whereas no significant increase occurred in the control leg (P greater than 0.05). It is concluded that during exercise glucose is formed from glycogen through the debranching enzyme when muscle glycogen is decreased to values below about 200 mmol/kg dry wt.     

IMP production and energy metabolism during exercise in rats in relation to age.

IMP production in and force exerted by rat quadriceps muscle in situ during various types of exercise were examined in relation to age. During continuous isometric exercise with constant stimulation time, the amount of IMP was linearly and inversely related to the age of the animals; a higher IMP concentration was found in intermittent isometric and dynamic exercise. No relationship was found between the total AMP deaminase activity and age. Exercise influenced neither the total activity nor the activity in the soluble fraction. From the results it is concluded that: the IMP concentration is linearly related to the free intracellular ATP4-/ADP3- ratio and the free AMP2- concentration; older animals are better able to maintain a high intramuscular ATP4-/ADP3- ratio and a low AMP2- concentration; IMP is produced in particular under conditions when the muscle has to work under extreme stress. IMP possibly exerts a feed-back control on the contraction system.     

Muscle metabolic responses during 16 hours of intermittent heavy exercise

The alterations in muscle metabolism were investigated in response to repeated sessions of heavy intermittent exercise performed over 16 h. Tissue samples were extracted from the vastus lateralis muscle before (B) and after (A) 6 min of cycling at approximately 91% peak aerobic power at repetitions one (R1), two (R2), nine (R9), and sixteen (R16) in 13 untrained volunteers (peak aerobic power = 44.3 +/- 0.66 mL.kg-1.min-1, mean +/- SE). Metabolite content (mmol.(kg dry mass)-1) in homogenates at R1 indicated decreases (p < 0.05) in ATP (21.9 +/- 0.62 vs. 17.7 +/- 0.68) and phosphocreatine (80.3 +/- 2.0 vs. 8.56 +/- 1.5) and increases (p < 0.05) in inosine monophosphate (IMP, 0.077 +/- 0.12 vs. 3.63 +/- 0.85) and lactate (3.80 +/- 0.57 vs. 84.6 +/- 10.3). The content (micromol.(kg dry mass)-1) of calculated free ADP ([ADPf], 86.4 +/- 5.5 vs. 1014 +/- 237) and free AMP ([AMPf], 0.32 +/- 0.03 vs. 78.4 +/- 31) also increased (p < 0.05). No differences were observed between R1 and R2. By R9 and continuing to R16, pronounced reductions (p < 0.05) at A were observed in IMP (72.2%), [ADPf] (58.7%), [AMPf] (85.5%), and lactate (41.3%). The 16-hour protocol resulted in an 89.7% depletion (p < 0.05) of muscle glycogen. Repetition-dependent increases were also observed in oxygen consumption during exercise. It is concluded that repetitive heavy exercise results in less of a disturbance in phosphorylation potential, possibly as a result of increased mitochondrial respiration during the rest-to-work non-steady-state transition.     

Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle.

To investigate the effect of exercise on GLUT-4, hexokinase, and glycogenin gene expression in human skeletal muscle, 10 untrained subjects (6 women and 4 men, 21.4 +/- 1.2 yr, 66.3 +/- 5.0 kg, peak oxygen consumption = 2.30 +/- 0.19 l/min) exercised for 60 min on a cycle ergometer at a power output requiring 73 +/- 4% peak oxygen consumption. Muscle samples were obtained by needle biopsy before, immediately after, and 3 h after exercise. Gene expression was quantified, relative to 29S ribosomal protein cDNA, by RT-PCR. GLUT-4 gene expression was increased immediately after exercise (1.7 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05) and remained significantly higher than baseline 3 h after the end of exercise (2. 2 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05). Hexokinase II gene expression was significantly higher than the resting value 3 h after the end of exercise (2.9 +/- 0.4 vs. 1.3 +/- 0.3 arbitrary units; P < 0.05). Exercise increased glycogenin mRNA more than twofold (2.8 +/- 0.6 vs. 1.2 +/- 0.2 arbitrary units; P < 0.05) 3 h after the end of exercise. For the first time, we report that a single bout of exercise is sufficient to cause upregulation of GLUT-4 and glycogenin gene expression in human skeletal muscle. Whether these increases, together with the associated increase in hexokinase II gene expression, lead to increased expression of these key proteins in skeletal muscle and contribute to the enhanced skeletal muscle glucose uptake, glycogen synthesis, and insulin action observed following exercise remains to be determined.     

Effect of carbohydrate ingestion on ammonia metabolism during exercise in humans.

The present study was undertaken to examine the effect of carbohydrate ingestion on plasma and muscle ammonia (NH(3) denotes ammonia and ammonium) accumulation during prolonged exercise. Eleven trained men exercised for 2 h at 65% peak pulmonary oxygen consumption while ingesting either 250 ml of an 8% carbohydrate-electrolyte solution every 15 min (CHO) or an equal volume of a sweet placebo. Blood glucose and plasma insulin levels during exercise were higher in CHO, but plasma hypoxanthine was lower after 120 min (1.7 +/- 0.3 vs. 2.6 +/- 0.1 micromol/l; P < 0. 05). Plasma NH(3) levels were similar at rest and after 30 min of exercise in both trials but were lower after 60, 90, and 120 min of exercise in CHO (62 +/- 9 vs. 76 +/- 9 micromol/l; P < 0.05). Muscle NH(3) levels were similar at rest and after 30 min of exercise but were lower after 120 min of exercise in CHO (1.51 +/- 0.21 vs. 2.07 +/- 0.23 mmol/kg dry muscle; P < 0.05; n = 5). These data are best explained by carbohydrate ingestion reducing muscle NH(3) production from amino acid degradation, although a small reduction in net AMP catabolism within the contracting muscle may also make a minor contribution to the lower tissue NH(3) levels.