Function of M-line-bound creatine kinase as intramyofibrillar ATP regenerator at the receiving end of the phosphorylcreatine shuttle in muscle.

Wallimann, Theo; Schlösser, Thomas; Eppenberger, Hans M.

doi:10.1016/s0021-9258(17)42981-4

Cited by 184 publications

(21 citation statements)

References 37 publications

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“…Specific enzyme activities were determined in the pH-stat assay [28,29], measuring the initial velocity of the reverse reaction (ATP production) at pH 7.0 and 25 mC in the presence of 4 mM ADP, 10 mM phosphocreatine (PCr), 10 mM MgCl # , 75 mM KCl, 0.1 mM EGTA and 1 mM β-mercaptoethanol. The Michaelis-Menten constants V max,rev , K ADP m and K PCr m were determined by measuring the initial velocity of the reverse reaction under the same conditions as above, but varying the ADP concentration between 0.05 and 10 mM, and the PCr concentration between 0.25 and 50 mM, sometimes even up to 100 mM.…”

Section: Ck Activity Measurementsmentioning

confidence: 99%

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics

Stolz

Hornemann²,

Schlattner³

et al. 2002

Biochem. J.

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Muscle-type creatine kinase (MM-CK) is a member of an isoenzyme family with key functions in cellular energetics. It has become a matter of debate whether the enzyme is autophosphorylated, as reported earlier [Hemmer, Furter-Graves, Frank, Wallimann and Furter (1995) Biochim. Biophys. Acta 1251, 81-90], or exclusively nucleotidylated. In the present paper, we demonstrate unambiguously that CK is indeed autophosphorylated. However, this autophosphorylation is not solely responsible for the observed microheterogeneity of MM-CK on two-dimensional isoelectric focusing gels. Using phosphoamino-acid analysis of (32)P-labelled CK isoforms, phosphothreonine (P-Thr) residues were identified as the only product of autophosphorylation for all CK isoenzymes. The phosphorylated residues in chicken MM-CK were allocated to a region in the vicinity of the active site, where five putative phosphorylation sites were identified. Site-directed threonine-valine-replacement mutants reveal that autophosphorylation is not specific for one particular residue but occurs at all examined threonine residues. The enzyme kinetic parameters indicate that the autophosphorylation of CK exerts a modulatory effect on substrate binding and the equilibrium constant, rather than on the catalytic mechanism itself.

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Section: Ck Activity Measurementsmentioning

confidence: 99%

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics

Stolz

Hornemann²,

Schlattner³

et al. 2002

Biochem. J.

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“…The association between this monomeric form and a nonglycosylated form of bovSERPINA3-7 can achieve a complex of 96 kDa, as observed. In addition, it is well documented that creatine kinase M-type is located in the M-band of the sarcomere [48] where it interacts with myomesin and M protein [49], especially in fast-twitch skeletal muscles [50]. More recently, computational simulations to predict creatine kinase-associated factors [51] have shown that creatine kinase M-type can potentially interact with 85 significant partners.…”

Section: Discussionmentioning

confidence: 99%

Expression of SERPINA3s in cattle: focus on bovSERPINA3-7 reveals specific involvement in skeletal muscle

et al. 2015

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α1-Antichymotrypsin is encoded by the unique SERPINA3 gene in humans, while it is encoded by a cluster of eight closely related genes in cattle. BovSERPINA3 proteins present a high degree of similarity and significant divergences in the reactive centre loop (RCL) domains which are responsible for the antiprotease activity. In this study, we analysed their expression patterns in a range of cattle tissues. Even if their expression is ubiquitous, we showed that the expression levels of each serpin vary in different tissues of 15-month-old Charolais bulls. Our results led us to focus on bovSERPINA3-7, one of the two most divergent members of the bovSERPINA3 family. Expression analyses showed that bovSERPINA3-7 protein presents different tissue-specific patterns with diverse degrees of N-glycosylation. Using a specific antibody raised against bovSERPINA3-7, Western blot analysis revealed a specific 96 kDa band in skeletal muscle. BovSERPINA3-7 immunoprecipitation and mass spectrometry revealed that this 96 kDa band corresponds to a complex of bovSERPINA3-7 and creatine kinase M-type. Finally, we reported that the bovSERPINA3-7 protein is present in slow-twitch skeletal myofibres. Precisely, bovSERPINA3-7 specifically colocalized with myomesin at the M-band region of sarcomeres where it could interact with other components such as creatine kinase M-type. This study opens new prospects on the bovSERPINA3-7 function in skeletal muscle and promotes opportunities for further understanding of the physiological role(s) of serpins.

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“…This does not affect enzymatic activity, but causes its localization to specific subcellular compartments (e.g., endoplasmic reticulum) as well as its co-localization with the highly energy-demanding SERCA. Moreover, it has been shown that a decrease in intracellular pH in muscle activates MM-CK to facilitate ATP regeneration [96], which might be expected after heightened muscle activity if we consider the optimum pH of this enzyme is between 6.5 and 6.7 [97].…”

Section: Ck Isozymesmentioning

confidence: 99%

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

et al. 2021

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Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

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Function of M-line-bound creatine kinase as intramyofibrillar ATP regenerator at the receiving end of the phosphorylcreatine shuttle in muscle.

Cited by 184 publications

References 37 publications

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics

Expression of SERPINA3s in cattle: focus on bovSERPINA3-7 reveals specific involvement in skeletal muscle

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

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