Smaller muscle ATP reduction in women than in men by repeated bouts of sprint exercise.

It was hypothesized that the reduction of high-energy phosphates in muscle after repeated sprints is smaller in women than in men. Fifteen healthy and physically active women and men with an average age of 25 yr (range of 19-42 yr) performed three 30-s cycle sprints (Wingate test) with 20 min of rest between sprints. Repeated blood and muscle samples were obtained. Freeze-dried pooled muscle fibers of types I and II were analyzed for high-energy phosphates and their breakdown products and for glycogen. Accumulation of plasma ATP breakdown products, plasma catecholamines, and blood lactate, as well as glycogen reduction in type I fibers, was all lower in women than in men during sprint exercise. Repeated sprints induced smaller reduction of ATP and smaller accumulation of IMP and inosine in women than in men in type II muscle fibers, with no gender differences in changes of ATP and its breakdown products during the bouts of exercise themselves. This indicates that the smaller ATP reduction in women than in men during repeated sprints was created during recovery periods between the sprint exercises and that women possess a faster recovery of ATP via reamination of IMP during these recovery periods.     

Effects of prior exercise on muscle metabolism during sprint exercise in horses.

The effect of warm-up exercise on energy metabolism and muscle glycogenolysis during sprint exercise (Spr) was examined in six fit Standardbred horses exercised at 115% of maximal O(2) consumption (VO(2 max)) until fatigued, 5 min after each of three protocols: 1) no warm-up (NWU); 2) 10 min at 50% of VO(2 max) [low-intensity warm-up (LWU)]; and 3) 7 min at 50% VO(2 max) followed by 45-s intervals at 80, 90, and 100% VO(2 max) [high-intensity warm-up (HWU)]. Warm-up increased (P < 0.0001) muscle temperature (T(m)) at the onset of Spr in LWU (38.3 +/- 0.2 degrees C) and HWU (40.0 +/- 0. 3 degrees C) compared with NWU (36.6 +/- 0.2 degrees C), and the rate of rise in T(m) during Spr was greater in NWU than in LWU and HWU (P < 0.01). Peak VO(2) was higher and O(2) deficit lower (P < 0. 05) when Spr was preceded by warm-up. Rates of muscle glycogenolysis were lower (P < 0.05) in LWU, and rates of blood and muscle lactate accumulation and anaerobic ATP provision during Spr were lower in LWU and HWU compared with NWU. Mean runtime (s) in LWU (173 +/- 10 s) was greater than HWU (142 +/- 11 s) and NWU (124 +/- 4 s) (P < 0. 01). Warm-up was associated with augmentation of aerobic energy contribution to total energy expenditure, decreased glycogenolysis, and longer run time to fatigue during subsequent sprint exercise, with no additional benefit from HWU vs. LWU.     

Effect of short-term sprint interval training on human skeletal muscle carbohydrate metabolism during exercise and time-trial performance.

Our laboratory recently showed that six sessions of sprint interval training (SIT) over 2 wk increased muscle oxidative potential and cycle endurance capacity (Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, and Gibala MJ. J Appl Physiol 98: 1895-1900, 2005). The present study tested the hypothesis that short-term SIT would reduce skeletal muscle glycogenolysis and lactate accumulation during exercise and increase the capacity for pyruvate oxidation via pyruvate dehydrogenase (PDH). Eight men [peak oxygen uptake (VO2 peak)=3.8+/-0.2 l/min] performed six sessions of SIT (4-7x30-s "all-out" cycling with 4 min of recovery) over 2 wk. Before and after SIT, biopsies (vastus lateralis) were obtained at rest and after each stage of a two-stage cycling test that consisted of 10 min at approximately 60% followed by 10 min at approximately 90% of VO2 peak. Subjects also performed a 250-kJ time trial (TT) before and after SIT to assess changes in cycling performance. SIT increased muscle glycogen content by approximately 50% (main effect, P=0.04) and the maximal activity of citrate synthase (posttraining: 7.8+/-0.4 vs. pretraining: 7.0+/-0.4 mol.kg protein -1.h-1; P=0.04), but the maximal activity of 3-hydroxyacyl-CoA dehydrogenase was unchanged (posttraining: 5.1+/-0.7 vs. pretraining: 4.9+/-0.6 mol.kg protein -1.h-1; P=0.76). The active form of PDH was higher after training (main effect, P=0.04), and net muscle glycogenolysis (posttraining: 100+/-16 vs. pretraining: 139+/-11 mmol/kg dry wt; P=0.03) and lactate accumulation (posttraining: 55+/-2 vs. pretraining: 63+/-1 mmol/kg dry wt; P=0.03) during exercise were reduced. TT performance improved by 9.6% after training (posttraining: 15.5+/-0.5 vs. pretraining: 17.2+/-1.0 min; P=0.006), and a control group (n=8, VO2 peak=3.9+/-0.2 l/min) showed no change in performance when tested 2 wk apart without SIT (posttraining: 18.8+/-1.2 vs. pretraining: 18.9+/-1.2 min; P=0.74). We conclude that short-term SIT improved cycling TT performance and resulted in a closer matching of glycogenolytic flux and pyruvate oxidation during submaximal exercise.     

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

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% O(2) (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 P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) 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 [P(i)]. At the end of exercise, PDH(a) was 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.     

ATP production and efficiency of human skeletal muscle during intense exercise: effect of previous exercise

The aim of the present study was to examine whether ATP production increases and mechanical efficiency decreases during intense exercise and to evaluate how previous exercise affects ATP turnover during intense exercise. Six subjects performed two (EX1 and EX2) 3-min one-legged knee-extensor exercise bouts [66.2 +/- 3.9 and 66.1 +/- 3.9 (+/-SE) W] separated by a 6-min rest period. Anaerobic ATP production, estimated from net changes in and release of metabolites from the active muscle, was 3.5 +/- 1.2, 2.4 +/- 0.6, and 1.4 +/- 0.2 mmol ATP x kg dry wt(-1) x s(-1) during the first 5, next 10, and remaining 165 s of EX1, respectively. The corresponding aerobic ATP production, determined from muscle oxygen uptake, was 0.7 +/- 0.1, 1.4 +/- 0.2, and 4.7 +/- 0.4 mmol ATP x kg dry wt(-1) x s(-1), respectively. The mean rate of ATP production during the first 5 s and next 10 s was lower (P < 0.05) than during the rest of the exercise (4.2 +/- 1.2 and 3.8 +/- 0.7 vs. 6.1 +/- 0.3 mmol ATP x kg dry wt(-1) x s(-1)). Thus mechanical efficiency, expressed as work per ATP produced, was lowered (P < 0.05) in the last phase of exercise (39.6 +/- 6.1 and 40.7 +/- 5.8 vs. 25.0 +/- 1.3 J/mmol ATP). The anaerobic ATP production was lower (P < 0.05) in EX2 than in EX1, but the aerobic ATP turnover was higher (P < 0.05) in EX2 than in EX1, resulting in the same muscle ATP production in EX1 and EX2. The present data suggest that the rate of ATP turnover increases during intense exercise at a constant work rate. Thus mechanical efficiency declines as intense exercise is continued. Furthermore, when intense exercise is repeated, there is a shift toward greater aerobic energy contribution, but the total ATP turnover is not significantly altered.     

alpha 1-Adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise

Attenuation of sympathetic vasoconstriction(sympatholysis) in working muscles during dynamic exercise iscontroversial. One potential mechanism is a reduction in₁-adrenergic-receptorresponsiveness. The purpose of this study was to examine₁-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogswere instrumented chronically with flow probes on the external iliacarteries of both hindlimbs and a catheter in one femoral artery. Aselective ₁-adrenergic-receptoragonist (phenylephrine) was infused as a bolus into the femoral arterycatheter at rest and during exercise. All dogs ran on amotorized treadmill at two exercise intensities (3 and 6 miles/h).Intra-arterial infusions of the same effective concentration ofphenylephrine elicited reductions in vascular conductance of 76 ± 4, 76 ± 6, and 67 ± 5% (P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic bloodpressure and blood flow in the contralateral iliac artery wereunaffected by phenylephrine. These results do not demonstrate anattenuation of vasoconstriction to a selective ₁-agonist during exercise anddo not support the concept of sympatholysis.

     

Regulation of muscle carbohydrate metabolism during exercise.

This review examines the mechanisms that regulate muscle carbohydrate metabolism during exercise. Muscle carbohydrate utilization is regulated primarily by two factors, namely, delivery of substrate to the glycolytic pathway either from glycogenolysis or from transport of extracellular glucose into the fibers, and formation of triosephosphate by phosphofructokinase. The regulation involves the integration of the glycolytic controls with other metabolic controls and the needs of the whole muscle in meeting the physiological demand. The controls operating in the glycolytic sequence in vivo appear to couple glycolytic recruitment to signals from the rate of energy demand, the TCA cycle state, and the mitochondrial redox state so as to satisfy the major regulatory goal of maintaining the supply of ATP for tension development.     

Skeletal muscle metabolism during high-intensity sprint exercise is unaffected by dichloroacetate or acetate infusion.

This study investigated whether increased provision of oxidative substrate would reduce the reliance on nonoxidative ATP production and/or increase power output during maximal sprint exercise. The provision of oxidative substrate was increased at the onset of exercise by the infusion of acetate (AC; increased resting acetylcarnitine) or dichloroacetate [DCA; increased acetylcarnitine and greater activation of pyruvate dehydrogeanse (PDH-a)]. Subjects performed 10 s of maximal cycling on an isokinetic ergometer on three occasions after either DCA, AC, or saline (Con) infusion. Resting PDH-a with DCA was increased significantly over AC and Con trials (3.58 +/- 0.4 vs. 0.52 +/- 0.1 and 0.74 +/- 0.1 mmol. kg wet muscle(-1). min(-1)). DCA and AC significantly increased resting acetyl-CoA (35.2 +/- 4.4 and 22.7 +/- 2.9 vs. 10.2 +/- 1.3 micromol/kg dry muscle) and acetylcarnitine (12.9 +/- 1.4 and 11.0 +/- 1.0 vs. 3.3 +/- 0.6 mmol/kg dry muscle) over Con. Resting contents of phosphocreatine, lactate, ATP, and glycolytic intermediates were not different among trials. Average power output and total work done were not different among the three 10-s sprint trials. Postexercise, PDH-a in AC and Con trials had increased significantly but was still significantly lower than in DCA trial. Acetyl-CoA did not increase in any trial, whereas acetylcarnitine increased significantly only in DCA. Exercise caused identical decreases in ATP and phosphocreatine and identical increases in lactate, pyruvate, and glycolytic intermediates in all trials. These data suggest that there is an inability to utilize extra oxidative substrate (from either stored acetylcarnitine or increased PDH-a) during exercise at this intensity, possibly because of O(2) and/or metabolic limitations.     

Regulation of ATP supply in mammalian skeletal muscle during resting state-->intensive work transition

In the present debating paper, the problem how the rate of ATP supply by oxidative phosphorylation in mitochondria is adjusted to meet a greatly increased demand for ATP during intensive exercise of skeletal muscle is discussed. Different experimental results are collected from different positions of the literature and confronted with five conceptual models of the regulation of the oxidative phosphorylation system. The previously performed computer simulations using a dynamic model of oxidative phosphorylation are also discussed in this context. The possible regulatory mechanisms considered in the present article are: (A) output activation: an external effector activates directly only the output of the system (ATP turnover); (B) input/output activation: an external effector activates directly the output (ATP usage) and input (substrate dehydrogenation) of the system; (C) removal of substrate shortage: only ATP consumption and substrate supply by blood are directly activated; (D) removal of oxygen shortage: only ATP consumption and oxygen supply by blood are directly activated; (E) each step activation: an external effector activates both the ATP-consuming subsystem and all the steps in the ATP-producing subsystem (particular enzymes/carriers/blocks of oxidative phosphorylation, substrate supply, oxygen supply). The performed confrontation of the considered mechanisms with the presented results leads to the conclusion that only the each step activation model is quantitatively consistent with the whole set of experimental data discussed. It is therefore postulated that a universal effector/regulatory mechanism of a still unknown nature which activates all steps of oxidative phosphorylation should exist and be discovered. A possible nature of such an effector is shortly discussed.     

Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans.

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.     

Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running.

We examined whether the quantity of exercise performed influences the expression of monocarboxylate transporter (MCT) 1 and MCT4 in mouse skeletal muscles (plantaris, tibialis anterior, soleus) and heart. Wheel running exercise (1, 3, and 6 wk) was used, which results in marked variations in self-selected running activity. Differences in muscle MCT1 and MCT4 among animals, before the initiation of running, were not related to the quantity of exercise performed on the first day of wheel running. No changes in MCT4 were observed over the course of the study (P > 0.05). After 6 wk of running, were there significant increases in heart (50%; P < 0.05) and muscle MCT1 (31-60%; P < 0.05) but not after 1 and 3 wk (P > 0.05). Because skeletal muscle MCT1 and running distances varied considerably, we examined the relationship between these two parameters. Within the first week of training, MCT1 was negatively correlated with the accumulated running distance (r = -0.70, P < 0.05). On further analysis, it appears that, in the first week, excessive running (>20 km/wk) represses MCT1 (-16.1%; P < 0.05), whereas more modest amounts of running (<20 km/wk) increase MCT1 (+37%; P < 0.05). After 3 wk of running, a positive relationship was observed between MCT1 and running distance (r = +0.76), although there is a threshold that must be exceeded before an increase over the control animals occurs. Finally, in week 6, when MCT1 was increased in the tibialis anterior and plantaris muscles, there were no correlations with the accumulated running distances. These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training.     

Regulation of muscle pyruvate metabolism during exercise

Pyruvate dehydrogenase and phosphoenolpyruvate carboxykinase are important enzymes in the regulation of muscle pyruvate metabolism and their in vitro measured activities have been studied in muscle from rested and exercised rats. In addition, the muscle concentration of metabolic intermediates associated with pyruvate metabolism has been measured after exercise. Phosphoenolpyruvate concentration was decreased to less than half the value found in rested muscle but pyruvate concentration did not change. This suggests an increase in the in vivo rate of conversion of phosphoenolpyruvate to pyruvate. Concentrations of malate and aspartate increased two- to threefold which suggests that oxaloacetate concentration was also increased. An increase in oxaloacetate availability would increase acetyl CoA metabolism and therefore would increase pyruvate dehydrogenase activity in vivo. The basal activity of pyruvate dehydrogenase measured in vitro increased approximately twofold after 2 hr of exercise and returned to control values 5 min after the cessation of exercise. Total pyruvate dehydrogenase activity (activated to the maximal extent) was not changed by exercise. Muscle PEPCK activity was also increased during exercise suggesting an increased rate of conversion of oxaloacetate to pyruvate to provide net oxidation of oxaloacetate and other citric acid cycle intermediates. Results of this study demonstrate that the rates of formation and metabolism of pyruvate are increased during exercise.     

Compartmentalized ATP synthesis in skeletal muscle triads.

Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads.     

Autonomic control of skeletal muscle vasodilation during exercise

Buckwalter, John B., Patrick J. Mueller, and Philip S. Clifford. Autonomic control of skeletal muscle vasodilation duringexercise. J. Appl. Physiol. 83(6):2037-2042, 1997.Despite extensive investigation, the control ofblood flow during dynamic exercise is not fully understood. The purposeof this study was to determine whether -adrenergic or muscarinicreceptors are involved in the vasodilation in exercising skeletalmuscle. Six mongrel dogs were instrumented with ultrasonic flow probeson both external iliac arteries and with a catheter in a branch of onefemoral artery. The dogs exercised on a treadmill at 6 miles/h whiledrugs were injected intra-arterially into one hindlimb. Isoproterenol(0.2 µg) or acetylcholine (1 µg) elicited increases in iliac bloodflow of 89.8 ± 14.4 and 95.6 ± 17.4%, respectively, withoutaffecting systemic blood pressure or blood flow in the contralateraliliac artery. Intra-arterial propranolol (1 mg) or atropine (500 µg)had no effect on iliac blood flow, although they abolished theisoproterenol and acetylcholine-induced increases in iliac blood flow.These data indicate that exogenous activation of -adrenergic ormuscarinic receptors in the hindlimb vasculature increases blood flowto dynamically exercising muscle. More importantly, because neitherpropranolol nor atropine affected iliac blood flow, we conclude that-adrenergic and muscarinic receptors are not involved in the controlof blood flow to skeletal muscle during moderate steady-state dynamicexercise in dogs.

     

Regulation of glycolysis in skeletal muscle.

Four hypotheses to explain the several hundred fold activation of phosphofructokinase and thus glycolysis in muscle during muscular contraction were examined. They are (1) Adenine nucleotide control. (2) An extension of the above hypothesis with 5′ AMP amplifying the change in glycolytic flux by modifying the phosphofructokinase/fructose 1, 6 diphosphatase cycle. (3) Synergistic activation of phosphofructokinase and compartmentation of phosphofructokinase in the sarcoplasmic reticulum.It is concluded that synergism among the effectors of phosphofructokinase is perhaps the major mechanism by which its activity is increased by several hundred folf during muscular contraction, and Ca⁺⁺ translocation during muscular contraction can activate 25–30% of total cellular phosphofructokinase that is located in the sacroplasmic reticulum.