Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

Perry, Stanton B.; McAuliffe, John J.; Balschi, James A.; Hickey, Paul R.; Ingwall, Joanne S.

doi:10.1021/bi00406a052

Cited by 62 publications

(39 citation statements)

References 23 publications

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“…In the fetal stage, CK-BB is almost exclusively expressed, whereas the CK-MM and CK-Mit isoenzymes are features of differentiation (13,44,50). The expression of CK-Mit has been correlated with the development of oxidative capacity in heart and brain (9,49), whereas levels of CK-MM correlate with the glycolytic capacity of muscle (30). The pattern of expression of CK isoenzymes changes during adaptation of muscle, with a decrease in CK-MM and an increase in CK-Mit with processes that convert fast-twitch toward slow-twitch muscle (37).…”

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confidence: 99%

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Askenasy

Koretsky

2002

American Journal of Physiology-Cell Physiology

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Askenasy, Nadir, and Alan P. Koretsky. Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels. Am J Physiol Cell Physiol 282: C338-C346, 2002. First published October 3, 2001 10.1152/ajpcell.00404.2001.-The function of creatine kinase (CK) and its effect on phosphorus metabolites was studied in livers of transgenic mice expressing human ubiquitous mitochondrial CK (CK-Mit) and rat brain CK (CK-B) isoenzymes and their combination.31 P NMR spectroscopy and saturation transfer were recorded in livers of anesthetized mice to measure high-energy phosphates and hepatic CK activity. CK reaction velocity was related to total enzyme activity irrespective of the isoenzyme expressed, and it increased with increasing concentrations of creatine (Cr). The fluxes mediated by both isoenzymes in both directions (phosphocreatine or ATP synthesis) were equal. Over a 20-fold increase in CK-Mit activity (28-560 mol ⅐ g wet wt Ϫ1 ⅐ min Ϫ1 ), the fraction of phosphorylated Cr increased 1.6-fold. Hepatic free ADP concentrations calculated by assuming equilibrium of the CK-catalyzed reaction in vivo decreased from 84 Ϯ 9 to 38 Ϯ 4 nmol/g wet wt. Calculated free ADP levels in mice expressing high levels of CK-B (920-1,635 mol ⅐ g wet wt Ϫ1 ⅐ min Ϫ1 ) were 52 Ϯ 6 nmol/g wet wt. Mice expressing both isoenzymes had calculated free ADP levels of 36 Ϯ 4 nmol/g wet wt. These findings indicate that CK-Mit catalyzes its reaction equally well in both directions and can lower hepatic apparent free ADP concentrations. mitochondrial creatine kinase; cytosolic creatine kinase; phosphorus-31 nuclear magnetic resonance spectroscopy; magnetization transfer; liver adenosine 5Ј-diphosphate concentration

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confidence: 99%

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Askenasy

Koretsky

2002

American Journal of Physiology-Cell Physiology

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“…It is not possible to compare the data in Figure 10 directly with the results presented in other figures, because in this experiment the oxygen consumption (workload) could not be kept the same for all CK levels. Also, the MiCK activity for the control group denoted as 100% of relative VCK in Figure 10 was only about 1/3 of the MiCK activity found in adult rabbit heart by other groups [12,16] implying the MiCK/MMCK ratio of activities 1/20 in these hearts instead of 1/6.…”

Section: Adequacy Of the Modelmentioning

confidence: 82%

“…The results are presented with respect to the relative activity of creatine kinase, VCK , where VCK = 1 corresponds to normal MiCK and MMCK activities in rabbit heart, 1.0 and 5.7 IU/mgdw, respectively [12,16] at T = 25…”

Section: Resultsmentioning

confidence: 99%

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Creatine kinase in energy metabolic signaling in muscle

Kongas

Beek

2007

Nature Precedings

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There has been much debate on the mechanism of regulation of mitochondrial ATP synthesis to balance ATP consumption during changing cardiac workloads. A key role of creatine kinase (CK) isoenzymes in this regulation of oxidative phosphorylation and in intracellular energy transport had been proposed, but has in the mean time been disputed for many years. It was hypothesized that high-energy phosphoryl groups are obligatorily transferred via CK; this is termed the phosphocreatine shuttle. The other important role ascribed to the CK system is its ability to buffer ADP concentration in cytosol near sites of ATP hydrolysis.Almost all of the experiments to determine the role of CK had been done in the steady state, but recently the dynamic response of oxidative phosphorylation to quick changes in cytosolic ATP hydrolysis has been assessed at various levels of inhibition of CK. Steady state models of CK function in energy transfer existed but were unable to explain the dynamic response with CK inhibited.The aim of this study was to explain the mode of functioning of the CK system in heart, and in particular the role of different CK isoenzymes in the dynamic response to workload steps. For this purpose we used a mathematical model of cardiac muscle cell energy metabolism containing the kinetics of the key processes of energy production, consumption and transfer pathways. The model underscores that CK plays indeed a dual role in the cardiac cells. The buffering role of CK system is due to the activity of myofibrillar CK (MMCK) while the energy transfer role depends on the activity of mitochondrial CK (MiCK). We propose that this may lead to the differences in regulation mechanisms and energy transfer modes in species with relatively low MiCK activity such as rabbit in comparison with species with high MiCK activity such as rat.The model needed modification to explain the new type of experimental data on the dynamic response of the mitochondria. We submit that building a Virtual Muscle Cell is not possible without continuous experimental tests to improve the model. In close interaction with experiments we are developing a model for muscle energy metabolism and transport mediated by the creatine kinase isoforms which now already can explain many different types of experiments. * On the leave

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“…Many investigations suggest that this enzyme is a basic diagnostic indicator useful in early detection of changes caused by pathological change of the muscle [8][9][10] . In this experiment, we observed a significant increase of CK in saline groups on day 3, and then decreased on day 7.…”

Section: Discussionmentioning

confidence: 99%

Effect of Energy Compound on Skeletal Muscle Strain Injury and Regeneration in Rats

Feng

et al. 2008

INDUSTRIAL HEALTH

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This study was designed to determine whether the supplement of energy compound could attenuate strain-induced damage to skeletal muscle in rats. Energy compound is a saline mixture of the following ingredients: ATP (10 mg), Coenzyme-A (50 units), Coenzyme-Q 10 (50 mg), Cytochrome C (30 mg) and Vitamin B 6 (50 mg). Experimental animals were injured in right gastrocnemius muscles by a strain injury model. Energy compound groups were given energy compound 10 ml/kg body weight per day since injured, while saline groups were given saline at the same dose. And a sham operation was performed on the right hindlimb of control group. Plasma was centrifuged to measure lactate dehydrogenase (LDH), lactic acid (La) and creatine kinase (CK) on 3, 7 and 14 d post injury. Muscles were removed and fixed for histology observation and immunohistochemistry assay of desmin and vimentin. The results showed a similar tendency of plasma CK, La and LDH in saline and energy compound groups, while the lower level was found in the energy-compound group. The histological examination of muscle sections revealed a lower degree of damage in the energy compound group in which the expression levels of desmin and vimentin were higher than in the saline group. It is suggested that energy compound supplement may attenuate strain-induced muscle damage and facilitate its regeneration.

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Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

Cited by 62 publications

References 23 publications

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Creatine kinase in energy metabolic signaling in muscle

Effect of Energy Compound on Skeletal Muscle Strain Injury and Regeneration in Rats

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