Phosphocreatine Resynthesis Research Articles

A Brief Review of the Use of Near Infrared Spectroscopy with Particular Interest in Resistance Exercise

There is growing interest in resistance training, but many aspects related to this type of exercise are still not fully understood. Performance varies substantially depending on how resistance training variables are manipulated. Fatigue is a complex phenomenon usually attributed to central (neuronal) and/or peripheral (muscular) origin. Cerebral oxygenation may be associated with the decision to stop exercise, and muscle oxygenation may be related to resistance training responses. Near infrared spectroscopy (NIRS) is a non-invasive optical technique used to monitor cerebral and muscle oxygenation levels. The purpose of this review is to briefly describe the NIRS technique, validation and reliability, and its application in resistance exercise. NIRS-measured oxygenation in cerebral tissue has been validated against magnetic resonance imaging during motor tasks. In muscle tissue, NIRS-measured oxygenation was shown to be highly related to venous oxygen saturation and muscle oxidative rate was closely related to phosphocreatine resynthesis, measured by (31)P-magnetic resonance spectroscopy after exercise. The test-retest reliability of cerebral and muscle NIRS measurements have been established under a variety of experimental conditions, including static and dynamic exercise. Although NIRS has been used extensively to evaluate muscle oxygenation levels during aerobic exercise, only four studies have used this technique to examine these changes during typical resistance training exercises. Muscle oxygenation was influenced by different resistance exercise protocols depending on the load or duration of exercise, the number of sets and the muscle being monitored. NIRS is a promising, non-invasive technique that can be used to evaluate cerebral and muscle oxygenation levels simultaneously during exercise, thereby improving our understanding of the mechanisms influencing performance and fatigue.

An Initial Phase of Phosphocreatine Recovery after Exercise with Flow Occlusion can be Explained by Glycogenolysis

PURPOSE: Classic studies (e.g., Sahlin, et al, Scand. J. Clin. Lab Invest. 39:551, 1979) suggested that phosphocreatine (PCr) resynthesis in human muscle after exercise is entirely dependent on oxidative metabolism. These results reinforce the view that glycogenolytic flux is strongly dependent on feedforward activation by calcium or other signals associated with contractile activity. In contrast, recent modeling studies (e.g., Lambeth and Kushmerick, Ann. Biomed. Eng. 30:808, 2002) suggest that the observed dependence of glycogenolysis on contractile activity is explained by strong coupling of the pathway to ATPase rate via classic feedback mechanisms. According to this modeling, glycogenolytically-driven PCr recovery ought to be observed under some conditions. METHODS: In this study, PCr resynthesis after 1 min of repetitive isometric ankle dorsiflexion exercise was measured in anterior tibial muscle of human subjects (n=4) by 31P-NMR spectroscopy (51.7 MHz, TR 3s) via a small surface coil under 3 conditions: no occlusion, partial flow occlusion (120 Torr cuff placed above knee), and near complete occlusion (160-180 Torr cuff). RESULTS: As expected, PCr recovery after exercise with no occlusion followed an exponential time course (see Figure top panel). In contrast, recovery during partial occlusion was biphasic, with a brief fast phase, followed by linear PCr recovery. During near-complete occlusion, only the brief, fast-phase of PCr recovery was observed. These three patterns of PCr recovery could be mimicked by a metabolic model in which glycogenolytic rate depends solely on changes in cytoplasmic AMP and inorganic phosphate (see Figure bottom panel).FigureFigureCONCLUSION: The results suggest that PCr recovery in human muscle is not entirely dependent on oxidative metabolism, and that feedforward mechanisms are not required to explain control of muscle glycogenolysis.

Mitochondrial respiration in creatine-loaded muscle: is there 31P-MRS evidence of direct effects of phosphocreatine and creatine in vivo?

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using 31P-magnetic resonance spectroscopy in 16 men and women (36.9 ± 4.6 yr). The initial PCr resynthesis rate and time constant (Tc) were used as indicators of mitochondrial respiration after brief (10–12 s) and exhaustive (1–4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr ( r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP ( r = 0.77, P < 0.001), and no relationship with end-exercise pH ( r = −0.14, P = 0.34). The PCr Tc was not as strongly related to PCr, Cr, PCr/Cr, and ADP ( r < 0.77, P < 0.001–0.18) and was significantly influenced by end-exercise pH ( r = −0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr Tc.

Muscle Fatigue during High-Intensity Exercise in Children

Children are able to resist fatigue better than adults during one or several repeated high-intensity exercise bouts. This finding has been reported by measuring mechanical force or power output profiles during sustained isometric maximal contractions or repeated bouts of high-intensity dynamic exercises. The ability of children to better maintain performance during repeated high-intensity exercise bouts could be related to their lower level of fatigue during exercise and/or faster recovery following exercise. This may be explained by muscle characteristics of children, which are quantitatively and qualitatively different to those of adults. Children have less muscle mass than adults and hence, generate lower absolute power during high-intensity exercise. Some researchers also showed that children were equipped better for oxidative than glycolytic pathways during exercise, which would lead to a lower accumulation of muscle by-products. Furthermore, some reports indicated that the lower ability of children to activate their type II muscle fibres would also explain their greater resistance to fatigue during sustained maximal contractions. The lower accumulation of muscle by-products observed in children may be suggestive of a reduced metabolic signal, which induces lower ratings of perceived exertion. Factors such as faster phosphocreatine resynthesis, greater oxidative capacity, better acid-base regulation, faster readjustment of initial cardiorespiratory parameters and higher removal of metabolic by-products in children could also explain their faster recovery following high-intensity exercise.From a clinical point of view, muscle fatigue profiles are different between healthy children and children with muscle and metabolic diseases. Studies of dystrophic muscles in children indicated contradictory findings of changes in contractile properties and the muscle fatigability. Some have found that the muscle of boys with Duchenne muscular dystrophy (DMD) fatigued less than that of healthy boys, but others have reported that the fatigue in DMD and in normal muscle was the same. Children with glycogenosis type V and VII and dermatomyositis, and obese children tolerate exercise weakly and show an early fatigue. Studies that have investigated the fatigability in children with cerebral palsy have indicated that the femoris quadriceps was less fatigable than that of a control group but the fatigability of the triceps surae was the same between the two groups. Further studies are required to elucidate the mechanisms explaining the origins of muscle fatigue in healthy and diseased children. The use of non-invasive measurement tools such as magnetic resonance imaging and magnetic resonance spectroscopy in paediatric exercise science will give researchers more insight in the future.

IS CHILDREN’S FASTER RECOVERY FROM EXERCISE DUE TO A HIGHER METABOLITE CLEARANCE RATE?

Dear Editor-in-Chief: We are writing regarding a recent article by Zafeiridis et al. (5), comparing recovery from high-intensity exercise in boys, adolescents, and adults. A faster recovery of performance capacity (knee flexion/extension) was demonstrated in children and adolescents compared with adults. It was concluded that recovery rate was maturity dependent. While the study and its results are well presented, we believe there is a significant discussion oversight regarding the mechanisms underlying this phenomenon. The authors speculate that a possible explanation may be a higher metabolite (lactate, H+) clearance rate in children: “Based on these facts, the possibility that the boys and teens in the current study had faster removal of lactate that facilitated the recovery process should not be excluded” (p. 511). The authors failed to consider the experimental evidence that contradicts their explanation. We addressed this very issue in a paper by Dotan et al. (1), which demonstrated, that blood lactate (La) disappearance rate following high-intensity exercise, is strikingly similar in children and adults, despite markedly different peak values ([La]peak). It was shown that not only was children’s La-disappearance half-time similar to that of adults, but that there was no difference between their La-recovery curves following similar [La]peak values. The only consistent difference being children’s shorter lag time to [La]peak. Therefore, it was argued that faster recovery in children is not due to a more efficient metabolite clearance rate, but rather to the fact that they have less to recover from (lower power output and La production) and that their [La]peak is reached sooner. The evidence of children’s lower sympathetic activation (3) that Zafeiridis et al. (5) cite in support of their view only supports our notion that children are anaerobically inferior, precisely because they are unable to fully mobilize their sympathetic system and recruit higher hierarchy motor units. This would explain their lower La production but not a faster La clearance. This is not to exclude other factors that separate boys from men (e.g., faster phosphocreatine resynthesis (2,4)). However, future research may well demonstrate that many or all of these differences stem from the alleged maturation-related difference in recruitment potential. Bareket Falk Raffy Dotan Brock University, Department of Physical Education and Kinesiology, St. Catharines, Ontario, Canada

Determination of muscle pH and glycolytic flux by magnetic resonance spectroscopy in contracting human skeletal muscle may have systematic errors

To the Editor : 31P magnetic resonance spectroscopy (MRS) is a powerful noninvasive technique to quantitatively assess phosphate metabolites and intracellular pH in vivo and has proven useful in describing the metabolic changes occurring in intact muscle. However, there are limitations and pitfalls

Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708-2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1-related DOA.

Magnetic resonance spectroscopy in patients with MELAS

Localized magnetic resonance spectroscopy (MRS) yields sensitive metabolic markers to provide insight into the pathophysiology of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in vivo. Findings in full MELAS syndrome at 1H MRS of the brain typically include severely elevated lactate and reduced N-acetylaspartate, glutamate, myo-inositol, and total creatine concentrations in stroke-like lesions. Similar but less extreme alterations are also common in gray matter (GM) regions that appear normal at magnetic resonance imaging. Phosphorus spectroscopy of peripheral muscle permits investigation of the bioenergetic status. A decline of the phosphorylation potential indicates a low energy reserve at rest. Phosphocreatine resynthesis during post-exercise recovery is delayed pointing to reduced mitochondrial capacity. As MRS is inherently non-invasive, follow-up studies can be performed to assess treatment response quantitatively.

Deficit of in vivo mitochondrial ATP production in OPA1‐related dominant optic atrophy

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708-2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1-related DOA.

Potential Ergogenic Effects of Arginine and Creatine Supplementation

The rationale for the use of nutritional supplements to enhance exercise capacity is based on the assumption that they will confer an ergogenic effect above and beyond that afforded by regular food ingestion alone. The proposed or advertised ergogenic effect of many supplements is based on a presumptive metabolic pathway and may not necessarily translate to quantifiable changes in a variable as broadly defined as exercise performance. L-arginine is a conditionally essential amino acid that has received considerable attention due to potential effects on growth hormone secretion and nitric oxide production. In some clinical circumstances (e.g., burn injury, sepsis) in which the demand for arginine cannot be fully met by de novo synthesis and normal dietary intake, exogenous arginine has been shown to facilitate the maintenance of lean body mass and functional capacity. However, the evidence that supplemental arginine may also confer an ergogenic effect in normal healthy individuals is less compelling. In contrast to arginine, numerous studies have reported that supplementation with the arginine metabolite creatine facilitates an increase in anaerobic work capacity and muscle mass when accompanied by resistance training programs in both normal and patient populations. Whereas improvement in the rate of phosphocreatine resynthesis is largely responsible for improvements in acute work capacity, the direct effect of creatine supplementation on skeletal muscle protein synthesis is less clear. The purpose of this review is to summarize the role of arginine and its metabolite creatine in the context of a nutrition supplement for use in conjunction with an exercise stimulus in both healthy and patient populations.

Impaired Muscle Metabolic Function in a Mitochondrial Myopathy Patient

0098 PURPOSE: Mitochondrial myopathy (MM) is a metabolic disorder, which may impair functional capacity during exercise and limit daily activity. We examined metabolic function in a 25-year old female patient with a possible mitochondrial disorder and an age matched healthy subject using simultaneous near infrared spectroscopy (NIRS) and 31P magnetic resonance spectroscopy (MRS) measures. METHODS: The MM patient and the healthy subject performed 12-second all out dynamic plantar flexion exercise and submaximal steady state (SS) plantar flexion exercise in a 2 Tesla, 75 cm bore MRS magnet. In both exercise protocols, subjects stopped the exercise when the medial gastrocnemius muscle phosphocreatine (PCr) level declined to 50% of the resting PCr. Muscle deoxygenation, reoxygenation, PCr, inorganic phosphate (Pi), ATP, and muscle pH during exercise and recovery were calculated from NIRS and MRS spectra. RESULTS: Compared to the healthy subject, the MM patient exhibited much slower rates of reoxygenation (T50: 15 s vs. 230 s) and PCr resynthesis (KPCr = 2.10 min−1 vs. 1.20 min−1) after 12-second exercise. At the onset of SS exercise, the MM patient showed much faster PCr breakdown (dPCr/dt: −4.12 %/s vs. −1.13 %/s) while Hb/Mb-deoxygenation was minimal compared to the healthy subject. In addition, the MM patient reached 50% of her resting PCr much faster than the healthy subject during steady state exercise protocol (1.5 minutes vs. 5 minutes). CONCLUSIONS: The nominal deoxygenation and faster PCr breakdown during exercise and the nominal reoxygenation and slower PCr resynthesis rates during recovery for the MM patient, indicate impaired mitochondrial oxidative capacity. These results suggest that NIRS may provide a reliable and relatively inexpensive means of assessing mitochondrial myopathies compared to MRS. Supported by NIH HL 44125

Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion.

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using (31)P-magnetic resonance spectroscopy in 16 men and women (36.9 +/- 4.6 yr). The initial PCr resynthesis rate and time constant (T(c)) were used as indicators of mitochondrial respiration after brief (10-12 s) and exhaustive (1-4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr (r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP (r = 0.77, P < 0.001), and no relationship with end-exercise pH (r = -0.14, P = 0.34). The PCr T(c) was not as strongly related to PCr, Cr, PCr/Cr, and ADP (r < 0.77, P < 0.001-0.18) and was significantly influenced by end-exercise pH (r = -0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr T(c).

ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery.

We used (31)P-magnetic resonance spectroscopy to study proton buffering in finger flexor muscles of eight healthy men (25-45 yr), during brief (18-s) voluntary finger flexion exercise (0.67-Hz contraction at 10% maximum voluntary contraction; 50/50 duty cycle) and 180-s recovery. Phosphocreatine (PCr) concentration fell 19 +/- 2% during exercise and then recovered with half time = 0.24 +/- 0.01 min. Cell pH rose by 0.058 +/- 0.003 units during exercise as a result of H(+) consumption by PCr splitting, which (assuming no lactate production or H(+) efflux) implies a plausible non-P(i) buffer capacity of 20 +/- 3 mmol. l intracellular water(-1). pH unit(-1). There was thus no evidence of significant glycogenolysis to lactate during exercise. Analysis of PCr kinetics as a classic linear response suggests that oxidative ATP synthesis reached 48 +/- 2% of ATP demand by the end of exercise; the rest was met by PCr splitting. Postexercise pH recovery was faster than predicted, suggesting "excess proton" production, with a peak value of 0.6 +/- 0.2 mmol/l intracellular water at 0.45 min of recovery, which might be due to, e.g., proton influx driven by cellular alkalinization, or a small glycolytic contribution to PCr resynthesis in recovery.

Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet–induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo.

Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

Muscle reoxygenation rate after isometric exercise at various intensities in relation to muscle oxidative capacity.

The purpose of this study was to determine whether the reoxygenation rate (Reoxy-rate) immediately after static exercise at various submaximal intensities would be related to muscle oxidative capacity. Seven healthy male subjects performed isometric handgrip exercise for 10 sec at 30%, 60% and 90% of maximal voluntary contraction (MVC). The Reoxy-rate and muscle oxygen consumption during exercise (muscle VO2EX) were monitored by near infrared continuous wave spectroscopy (NIRcws). The muscle oxidative capacity was evaluated by the time constant for phosphocreatine resynthesis (PCrTc) using 31-phosphorus magnetic resonance spectroscopy (31P-MRS). The Peak blood flow of brachial artery after exercise (BABFpeak) was measured using Doppler ultrasound. There was no correlation between PCrTc and Reoxy-rate at 30% and 60% MVC. In contrast, Reoxy-rate at 90% MVC was positively correlated to PCrTC (r = 0.825, p < 0.05). The muscle VO2EX increased 5.9, 8.8 and 12.6-fold of the resting on average at 30%, 60% and 90% MVC, respectively, and the muscle VO2EX at 90% MVC was significantly higher than that at 30% and 60% MVC. On the other hand, BABFpeak increased only just 1.9, 2.4 and 2.7-fold of the resting on average at 30%, 60% and 90% MVC, respectively (Fig. 4). These results suggest that the higher oxidative capacity muscle shows slower muscle reoxygenation after 10 sec isometric exercise at 90% MVC because the Reoxy-rate after this type of exercise may be influenced more by muscle VO2 than by O2 supply. In contrast, 60% MVC and lower exercise intensities may not be severe enough to influence the muscle VO2 dependent Reoxy-rate.

THE DOSE-RESPONSE RELATIONSHIP BETWEEN SHORT DURATION HIGH-INTENSITY EXERCISE AND EPOC.

This study examined the dose-response relationship between single bouts of short duration high-intensity exercise and the fast component of excess post-exercise oxygen consumption (EPOCFC). On three separate occasions, 21 active males (22 ± 0.6 years, 74.1 ± 2.0 kg, 55.5 ± 1.8 ml·kg−1·min−1) performed single all-out sprints of 5, 10 and 20 seconds (s) from a stationary start on a friction loaded cycle ergometer (.08kg·kg of body weight−1). EPOCFC was defined as the VO2 (ml), above resting O2 (ml·min−1), in the 3-minute period immediately following the end of the 5, 10 and 20s sprints.Table 1: Total Work (Joules) Performed In 5, 10 and 20s Sprints, and the Resulting EPOCFC (ml) and EPOCFC Per Minute (ml·min−1) for the 1st, 2nd and 3rd Minutes.Two-fold (5s to 10s) and four-fold (5s to 20s) increases in the duration of high-intensity exercise resulted in 37% and 95% increases in EPOCFC. Regardless of sprint duration, approximately 62% of the total VO2 (ml) occurred in the 1st minute of EPOCFC. This pattern parallels the resynthesis of Phosphocreatine, an oxygen dependent process, which is half completed in ≈ 1 minute. It was concluded that a systematic increase in the dose of short duration high-intensity exercise does not produce a proportional response on the fast component of EPOC.

Effect of creatine supplementation on phosphocreatine resynthesis, inorganic phosphate accumulation and pH during intermittent maximal exercise

In this study, we examined the effect of creatine ingestion on muscle power output, muscle phosphocreatine resynthesis, inorganic phosphate and pH during repeated brief bouts of maximal exercise. Nine healthy males performed maximal plantar flexion before and after creatine ingestion (20 g ·day -1 for 6 days). The experimental protocol consisted of five 8 s bouts (bouts 1-5) interspersed with 30 s recovery, followed by bouts 6 (8 s) and 7 (16 s) separated by 1 and 2 min, respectively. Muscle phosphocreatine, inorganic phosphate and pH were estimated every 16 s by 31 P magnetic resonance spectroscopy. After creatine ingestion, muscle power output increased by ~5% ( P ≪ 0.05) from bouts 3 to 7 and muscle phosphocreatine resynthesis increased ( P ≪ 0.05) during 10 min recovery. The higher phosphocreatine concentration observed after only 30 s of recovery was accompanied by lower inorganic phosphate accumulation and higher pH. Strong correlations were found between exercise power restoration and the corresponding pre-exercise phosphocreatine and inorganic phosphate concentrations and muscle pH after creatine ingestion. The better maintenance of muscle power output observed after creatine ingestion was attributed to a higher rate of phosphocreatine resynthesis, lower accumulation of inorganic phosphate and higher pH.

Magnetization‒transfer 31P NMR of biochemical exchange in vivo: Application to creatine kinase kinetics

Phosphorus‒31 saturation‒transfer NMR spectroscopy provides an elegant means to study fluxes through the creatine kinase reaction in human skeletal muscle. To obtain reliable quantitative kinetic information, experimental imperfections, such as incomplete saturation and radiofrequency bleed over need to be addressed appropriately. In resting muscle, creatine kinase was near equilibrium both in normal controls and in a patient with impaired oxidative phosphorylation. Oral intake of high doses of creatine monohydrate for several days resulted in significantly increased concentrations of phosphocreatine but had no measurable effect on the phosphocreatine resynthesis rate in resting muscle.

Factors affecting the rate of phosphocreatine resynthesis following intense exercise.

Within the skeletal muscle cell at the onset of muscular contraction, phosphocreatine (PCr) represents the most immediate reserve for the rephosphorylation of adenosine triphosphate (ATP). As a result, its concentration can be reduced to less than 30% of resting levels during intense exercise. As a fall in the level of PCr appears to adversely affect muscle contraction, and therefore power output in a subsequent bout, maximising the rate of PCr resynthesis during a brief recovery period will be of benefit to an athlete involved in activities which demand intermittent exercise. Although this resynthesis process simply involves the rephosphorylation of creatine by aerobically produced ATP (with the release of protons), it has both a fast and slow component, each proceeding at a rate that is controlled by different components of the creatine kinase equilibrium. The initial fast phase appears to proceed at a rate independent of muscle pH. Instead, its rate appears to be controlled by adenosine diphosphate (ADP) levels; either directly through its free cytosolic concentration, or indirectly, through its effect on the free energy of ATP hydrolysis. Once this fast phase of recovery is complete, there is a secondary slower phase that appears almost certainly rate-dependent on the return of the muscle cell to homeostatic intracellular pH. Given the importance of oxidative phosphorylation in this resynthesis process, those individuals with an elevated aerobic power should be able to resynthesise PCr at a more rapid rate than their sedentary counterparts. However, results from studies that have used phosphorus nuclear magnetic resonance ((31)P-NMR) spectroscopy, have been somewhat inconsistent with respect to the relationship between aerobic power and PCr recovery following intense exercise. Because of the methodological constraints that appear to have limited a number of these studies, further research in this area is warranted.