Ammonia and IMP in different skeletal muscle fibers after exercise in rats

Meyer, Ronald A.; Dudley, Gary A.; Terjung, Ronald L.

doi:10.1152/jappl.1980.49.6.1037

Cited by 127 publications

(57 citation statements)

References 21 publications

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“…In normal skeletal muscle the accumulation of free ADP is limited by several processes involved in ATP synthesis (glycolysis and oxidative phosphorylation) and ADP buffering (CK). Even when energy demands exceed the capacity for ATP synthesis such that a decline in ATP is observed, ADP removal is facilitated by the coupled reactions of AK and AMPD and the accumulation of IMP accounts for nearly the entire decline in ATP (20). The objective of this study was to determine whether the increase in ADP measured from muscle extracts under similar conditions in these mice was metabolically active free ADP.…”

Section: Discussionmentioning

confidence: 99%

³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

Hancock

Brault

Wiseman³

et al. 2005

American Journal of Physiology-Cell Physiology

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. 31 P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1. Am J Physiol Cell Physiol 288: C1298 -C1304, 2005. First published February 2, 2005 doi:10.1152/ajpcell.00621.2004.-Metabolic control within skeletal muscle is designed to limit ADP accumulation even during conditions where ATP demand is out of balance with ATP synthesis. This is accomplished by the reactions of adenylate kinase (AK; ADPϩ ADP 7 AMPϩATP) and AMP deaminase (AMPϩH 2O 3 NH 3ϩIMP), which limit ADP accumulation under these conditions. The purpose of this study was to determine whether AK deficiency (AK Ϫ/Ϫ ) would result in sufficient ADP accumulation to be visible using 31 P-NMRS during the high energy demands of frequent in situ tetanic contractions. To do this we examined the high-energy phosphates of the gastrocnemius muscle in the knockout mouse with AK1 Ϫ/Ϫ and wild-type (WT) control muscle over the course of 64 rapid (2/s) isometric tetanic contractions. Near-complete depletion of phosphocreatine was apparent after 16 contractions in both groups. By ϳ40 contractions, ADP was clearly visible in AK1 Ϫ/Ϫ muscle. This transient concentration of the NMR visible free ADP was estimated to be ϳ1.7 mM, and represents the first time free ADP has been directly measured in contracting skeletal muscle. Such an increase in free ADP is severalfold greater than previously thought to occur. This large accumulation of free ADP also represents a significant reduction in energy available from ATP, and has implications on cellular processes that depend on a high yield of energy from ATP such as calcium sequestration. Remarkably, the AK1 Ϫ/Ϫ and WT muscles exhibited similar fatigue profiles. Our findings suggest that skeletal muscle is surprisingly tolerant to a large increase in ADP and by extension, a decline in energy from ATP. muscle energetics; muscle relaxation; magnetic resonance spectroscopy IN NORMAL MUSCLE DURING EXERCISE the demand for ATP is adequately balanced by ATP supply from oxidative phosphorylation and glycolysis, coupled with the ATP buffering capacity of the creatine kinase reaction, such that ATP is not significantly depleted. Even when ATP demand does exceed ATP supply, and a decline in ATP is observed, the decline in ATP is not matched by a stoichiometric accumulation of ADP because of the action of adenylate kinase (AK), which transfers a phosphate from one ADP to another ADP resulting in ATP and AMP formation. In skeletal muscle the AMP formed from this reaction is rapidly deaminated by AMP deaminase (AMPD) resulting in the formation of inosine 5Ј-monophosphate (IMP). Thus, when the rate of ATP hydrolysis exceeds the ATP supply capacity, there is a stoichiometric accumulation of IMP, due to the coupled reactions of AK and AMPD. Therefore, at high energy demands, the reactions of AK and AMPD both serve to limit ADP accumulation.The importance of limiting ADP accumulation in skeletal muscle is implied by the apparent lack of such a limit on another product of ATP hydrolysis, in...

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Section: Discussionmentioning

confidence: 99%

³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

Hancock

Brault

Wiseman³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…Indeed, fibres devoid of ATP have been identified in equine muscle after exercise, but these have been attributed to experimental error ( Snow et al, 1985 ). It has been reported that deamination of AMP to IMP occurred rapidly in type-Il but not in type-I muscle fibres of rats during intense stimulation or strenuous exercise (Meyer, Dudley and Terjung, 1980;Meyer and Terjung, 1979) indicating, possibly, that the activity of AMP-deaminase is higher in type-Il than type-I fibres. Moreover, it has been shown in rat (Dudley and Terjung, 1985) and human muscle (Harris and Hultman, 1985) that during exercise IMP accumulation did not occur until muscle lactate content reached 50-75mrnol.Kg'dm.…”

Section: Metabolic Aspects Of Fatigue During High-intensity Exercisementioning

confidence: 99%

Human muscle metabolism during intermittent maximal exercise

Gaitanos

Williams

Boobis

et al. 1993

Journal of Applied Physiology

747

591

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Eight male subjects volunteered to take part in this study. The exercise protocol consisted of ten 6-s maximal sprints with 30 s of recovery between each sprint on a cycle ergometer. Needle biopsy samples were taken from the vastus lateralis muscle before and after the first sprint and 10 s before and immediately after the tenth sprint. The energy required to sustain the high mean power output (MPO) that was generated over the first 6-s sprint (870.0 +/- 159.2 W) was provided by an equal contribution from phosphocreatine (PCr) degradation and anaerobic glycolysis. Indeed, within the first 6-s bout of maximal exercise PCr concentration had fallen by 57% and muscle lactate concentration had increased to 28.6 mmol/kg dry wt, confirming significant glycolytic activity. However, in the tenth sprint there was no change in muscle lactate concentration even though MPO was reduced only to 73% of that generated in the first sprint. This reduced glycogenolysis occurred despite the high plasma epinephrine concentration of 5.1 +/- 1.5 nmol/l after sprint 9. In face of a considerable reduction in the contribution of anaerobic glycogenolysis to ATP production, it was suggested that, during the last sprint, power output was supported by energy that was mainly derived from PCr degradation and an increased aerobic metabolism.

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“…(7,19). Other studies have found that fast fibers exhibit a large depletion of ATP, while slow fibers maintain their ATP content near normal levels during intense stimulation conditions that produce rapid fatigue (20).…”

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confidence: 95%

Metabolic heterogeneity in human calf muscle during maximal exercise.

Vandenborne

McCully

Kakihira

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Human skeletal muscle is composed of various muscle fiber types. We hypothesized that differences in metabolism between fiber types could be detected noninvasively with 31P nuclear magnetic resonance spectroscopy during maximal exercise. This assumes that during maximal exercise all fiber types are recruited and all vary in the amount of acidosis. The calf muscles of seven subjects were studied. Two different coils were applied: an 11-cm-diameter surface coil and a five-segment meander coil. The meander coil was used to localize the 31p signal to either the medial or the lateral gastrocnemius. Maximal exercise, consisting of rapid plantar flexions, resulted in an 83.7% ± 7.8% decrease of the phosphocreatine pool and an 8-fold increase of the inorganic phosphate (Pi) pool. At rest the Pi pool was observed as a single resonance (pH 7.0). Toward the end of the first minute of exercise, three subjects showed three distinct Pi peaks. During the second minute of exercise the pH values stabilized at 7.12 ± 0.12, 6.63 ± 0.15, and 6.27 ± 0.23. The same pattern was seen when the signal was collected from the medial or lateral gastrocnemius. In four subjects only two distinct Pi peaks were observed. The Pi peaks had differing relative areas in different subjects, but they were reproducible in each individual. This method allowed us to study the appearance and disappearance of the different Pi peaks, together with the changes in pH.

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Ammonia and IMP in different skeletal muscle fibers after exercise in rats

Cited by 127 publications

References 21 publications

³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

Human muscle metabolism during intermittent maximal exercise

Metabolic heterogeneity in human calf muscle during maximal exercise.

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Ammonia and IMP in different skeletal muscle fibers after exercise in rats

Cited by 127 publications

References 21 publications

31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

Human muscle metabolism during intermittent maximal exercise

Metabolic heterogeneity in human calf muscle during maximal exercise.

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³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1

³¹P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1