Metabolic fluctuation during a muscle contraction cycle

Chung, Youngran; Sharman, Robert B.; Carlsen, Richard C.; Unger, Steven W.; Larson, Douglas E.; Jue, Thomas

doi:10.1152/ajpcell.1998.274.3.c846

Cited by 66 publications

(48 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a spatial ATP buffer, CK is important for maintaining high cytosolic ATP concentration at the site of utilization and low ADP concentration at the site of de novo ATP synthesis. CK also buffers ATP over time (6,48), and this buffering effect is likely important when energy demands vary widely during the cardiac cycle. In normal skeletal muscle, PCr acts as a rapid, transient source to replenish ATP by the CK reaction after each contraction, with changes in PCr observed on a millisecond time scale (6).…”

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

“…CK also buffers ATP over time (6,48), and this buffering effect is likely important when energy demands vary widely during the cardiac cycle. In normal skeletal muscle, PCr acts as a rapid, transient source to replenish ATP by the CK reaction after each contraction, with changes in PCr observed on a millisecond time scale (6). Cyclic changes in PCr during the cardiac-contraction cycle have also been described in some (49)(50)(51)(52), but not all (53)(54)(55) reports.…”

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

“…Cyclic changes in PCr during the cardiac-contraction cycle have also been described in some (49)(50)(51)(52), but not all (53)(54)(55) reports. To the extent that cardiac muscle shares some properties with skeletal muscle (6), rapid provision of ATP by CK with contraction would represent a potentially important mechanism by which a significant reduction in CK flux in heart failure could limit temporal buffering and, thereby, limit contractile ATP supply and function. In this light it is important to reconsider the current evidence on CK reserve as indexed by the time-averaged ratio of net CK flux to de novo ATP synthesis which our data predict would approach unity in some human heart failure settings.…”

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

“…CK reversibly converts ADP and creatine phosphate (PCr) to ATP and creatine (Cr). This reaction allows tight control of ADP and ATP concentrations in cardiac and skeletal muscle as well as in brain, providing a rapid source of ATP during ischemia and burst activity in skeletal muscle (4)(5)(6). It is also hypothesized that the CK reaction serves as an intracellular spatial energy shuttle, facilitating the transfer of high-energy phosphates from the mitochondria (where ATP is produced) to the cytosol (where ATP is used) and facilitating the return of products to the mitochondria for rephosphorylation (5,7).…”

mentioning

confidence: 99%

See 3 more Smart Citations

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Weiss

Gerstenblith

Bottomley

2005

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

294

348

View full text Add to dashboard Cite

The heart consumes more energy per gram than any other organ, and the creatine kinase (CK) reaction serves as its prime energy reserve. Because chemical energy is required to fuel systolic and diastolic function, the question of whether the failing heart is ''energy starved'' has been debated for decades. Despite the central role of the CK reaction in cardiac energy metabolism, direct measures of CK flux in the beating human heart were not previously possible. Using an image-guided molecular assessment of endogenous ATP turnover, we directly measured ATP flux through CK in normal, stressed, and failing human hearts. We show that cardiac CK flux in healthy humans is faster than that estimated through oxidative phosphorylation and that CK flux does not increase during a doubling of the heart rate-blood pressure product by dobutamine. Furthermore, cardiac ATP flux through CK is reduced by 50% in mild-to-moderate human heart failure (1.6 ؎ 0.6 vs. 3.2 ؎ 0.9 mol͞g of wet weight per sec, P < 0.0005). We conclude that magnetic resonance strategies can now directly assess human myocardial CK energy flux. The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of sufficient magnitude, even in the absence of a significant reduction in ATP stores, to contribute to the pathophysiology of human heart failure. These findings support the pursuit of new therapies that reduce energy demand and͞or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.heart failure ͉ magnetic resonance spectroscopy ͉ metabolism A TP provides the chemical energy that fuels myocardial contractile function. Relatively large rates of ATP synthesis are required to sustain normal systolic and diastolic function. The ''energy starvation'' hypothesis of heart failure suggests that inadequate ATP supply underlies the contractile dysfunction present in heart failure (1, 2). Large-scale clinical trials demonstrating that pharmacologic agents such as beta-blockers and angiotensin-converting enzyme inhibitors that reduce metabolic demand improve outcomes in heart failure, whereas those such as positive inotropic agents that increase energetic demand worsen outcomes (3) are consistent with the energy-starvation hypothesis. However, the ability to test the energy-starvation hypothesis has been limited, in part, by an inability to directly measure ATP synthesis in the human heart.Creatine kinase (CK) is central to mammalian energy metabolism and serves as the prime energy reserve of the heart. CK reversibly converts ADP and creatine phosphate (PCr) to ATP and creatine (Cr). This reaction allows tight control of ADP and ATP concentrations in cardiac and skeletal muscle as well as in brain, providing a rapid source of ATP during ischemia and burst activity in skeletal muscle (4-6). It is also hypothesized that the CK reaction serves as an intracellular spatial energy shuttle, facilitating the transfer of high-energy phosphates from the mitochondria (where AT...

show abstract

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Weiss

Gerstenblith

Bottomley

2005

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

294

348

View full text Add to dashboard Cite

show abstract

“…Of course, oxidative metabolism appears to be too slow to participate to this initial mechanism. Thus, in these conditions, [ATP] does not decrease, not even during the first few milliseconds after the onset of exercise (Chung et al, 1998) …”

Section: The Exercise Transient Periodmentioning

confidence: 86%

Saturation of the Lactate Clearance Mechanisms Different from the “Lactate Shuttle” Determines the Anaerobic Threshold: Prediction from the Bioenergetic Model

Binzoni

2005

J. Physiol. Anthropol.

View full text Add to dashboard Cite

It is demonstrated, that the bioenergetic model combined with the mathematical constraints determined by the experimental knowledge of the aerobic metabolism and the Lohmann reaction dictates the exact lactate (La)-time relationship during exercise. The theory predicts that La is necessarily produced (above the resting baseline), even during extremely low work loads, where the metabolism was usually considered in the past to be "pure" aerobic. The La rate of production increases linearly as a function of the work load. The anaerobic threshold is strictly determined by the saturation of the La clearance mechanisms of the body different from the "La shuttle" and not by the involvement of a sudden increased La production at the cellular level. These results imply that the half time of the PCr breakdown kinetics at the onset of a constant load exercise can be expressed as a function of the onset speed of the aerobic and of the anaerobic metabolism, even in the case of a very low mechanical power. The PCr halftime does not depend on the workload and represents a physiological invariant. The bioenergetic model was created during a long historical period, when it was believed that the La production was not present at all for very low exercise levels but, actually, the bioenergetic model predicts exactly the opposite result!

show abstract

Osteoinductivity of partially purified bovine, ostrich and emu bone morphogenetic proteins in vitro

Peel

et al. 2011

J Biomedical Materials Res

View full text Add to dashboard Cite

The aim of this study was to observe the osteogenic activity of native bone morphogenetic proteins (BMPs) obtained from different species including bovine, ostrich and emu sources in order to compare mammalian and avian BMPs. Rat mesenchymal progenitor marrow stromal cells and pre-osteoblastic C2C12 cell cultures, were exposed to the native BMPs and alkaline phosphatase (ALP) and creatine kinase (CK) levels were determined by assay. The results showed that the ALP activity in C2C12 cultures was elevated by bovine BMP by 2- to 10-fold (p < 0.05-0.001) from day 3 during 14 days. There were no significant differences in avian BMP related elevations of ALP activity except with ostrich BMPs at day 14 (p < 0.05). However, exposure of MSCs cultures to BMPs derived from bovine, ostrich or emu sources resulted in elevated ALP from day 3 (p < 0.05). Bovine BMP resulted in more ALP elevation than with either of the avian BMPs. All of BMPs elevated Creatine kinase (CK) activity from day 1 and climbed until peaking at day 7. Compared with control cultures, CK was elevated more with exposure to emu BMP and was more elevated with greater statistical significance than with bovine and ostrich BMP before day 5. These higher levels remained until day 14 (p < 0.05). The results of this study suggest that both bovine and avian BMPs are able to stimulate osteogenesis in mature osteoblasts in vitro. The strongest synergistic effect on osteogenesis was detected in cells stimulated with bovine BMP. Avian BMPs had lower effects on ALP and CK activity, emu BMP being more effective than ostrich BMP.

show abstract

Metabolic fluctuation during a muscle contraction cycle

Cited by 66 publications

References 33 publications

ATP flux through creatine kinase in the normal, stressed, and failing human heart

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Saturation of the Lactate Clearance Mechanisms Different from the “Lactate Shuttle” Determines the Anaerobic Threshold: Prediction from the Bioenergetic Model

Osteoinductivity of partially purified bovine, ostrich and emu bone morphogenetic proteins in vitro

Contact Info

Product

Resources

About

Metabolic fluctuation during a muscle contraction cycle

Cited by 66 publications

References 33 publications

ATP flux through creatine kinase in the normal, stressed, and failing human heart

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Saturation of the Lactate Clearance Mechanisms Different from the &ldquo;Lactate Shuttle&rdquo; Determines the Anaerobic Threshold: Prediction from the Bioenergetic Model

Osteoinductivity of partially purified bovine, ostrich and emu bone morphogenetic proteins in vitro

Contact Info

Product

Resources

About

Saturation of the Lactate Clearance Mechanisms Different from the “Lactate Shuttle” Determines the Anaerobic Threshold: Prediction from the Bioenergetic Model