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evolution
the MtCK gene is likely basal and ancestral and has evolved very early in metazoan evolution
malfunction
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absence of creatine kinase in muscle cells leads to morphological and functional adaptations towards preservation of muscle contractile abilities
malfunction
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complete brain-type creatine kinase deficiency in mice blocks seizure activity and affects intracellular calcium kinetics
malfunction
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oxygen consumption dynamics during electrical stimulation in superfused fast-twitch hindlimb muscles isolated from wild-type and transgenic mice deficient in the myoplasmic and mitochondrial creatine isoforms (MiM CK-/-), respectively. Transgenic mice deficient in the mitochondrial creatinine isoforms (MiM CK-/-) show muscle oxygen consumption activation kinetics 30% faster than wild-type. MiM CK-/- muscle oxygen consumption deactivation kinetics are 380% faster than wild-type
malfunction
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24 h after trauma brain injury (TBI) of mice preconditioned with N-methyl-D-aspartate, creatine kinase activity is augmented in the cerebral cortex. Eventhough N-methyl-D-aspartate preconditioning and TBI have similar effects on the enzyme activity, each manages its response via opposite mechanisms because the protective effects of preconditioning are unambiguous
malfunction
downregulation of brain-type creatine kinase in brain of a Huntington's disease mouse model. Huntington's disease is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Mutant HTT (mHTT) suppresses the activity of the CKB gene promoter, which contributes to the lowered CKB expression in Huntington's disease. Exogenous expression of wild-type CKB, but not a dominant negative CKB mutant, rescues the ATP depletion, aggregate formation, impaired proteasome activity, and shortened neurites induced by mHTT. Negative regulation of isozyme CKB by mHTT is a key event in the pathogenesis of Huntington's disease and contributes to the neuronal dysfunction associated with Huntington's disease
malfunction
downregulation of brain-type creatine kinase in brains of Huntington's disease patients. Huntington's disease is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene
malfunction
knockout mice that lack the brain CK isoforms, i.e. BCK and/or ubiquitous MtCK, uMtCK, show defects in spatial memory acquisition and behavior, development of the hippocampus, correct functioning of hair bundle cells in the auditory system, and energy distribution within photoreceptor cells, transgenic models of creatine deficiency, overview
malfunction
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impairment of enzyme activity leads to a downregulation of renal Na+, K+-ATPase activity during an Aeromonas caviae infection, contributing to energy depletion
malfunction
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downregulation of brain-type creatine kinase in brain of a Huntington's disease mouse model. Huntington's disease is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Mutant HTT (mHTT) suppresses the activity of the CKB gene promoter, which contributes to the lowered CKB expression in Huntington's disease. Exogenous expression of wild-type CKB, but not a dominant negative CKB mutant, rescues the ATP depletion, aggregate formation, impaired proteasome activity, and shortened neurites induced by mHTT. Negative regulation of isozyme CKB by mHTT is a key event in the pathogenesis of Huntington's disease and contributes to the neuronal dysfunction associated with Huntington's disease
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malfunction
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24 h after trauma brain injury (TBI) of mice preconditioned with N-methyl-D-aspartate, creatine kinase activity is augmented in the cerebral cortex. Eventhough N-methyl-D-aspartate preconditioning and TBI have similar effects on the enzyme activity, each manages its response via opposite mechanisms because the protective effects of preconditioning are unambiguous
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metabolism
co-localization and functional coupling of creatine kinase isoforms with ATP-producing and ATP-consuming reactions, a non-equilibrium state of the creatine kinase reaction, and restricted intracellular diffusion of adenine nucleotides support the concept of a cellular CK/PCr phosphoryl transfer network. spatial organization of the CK/PCr shuttle in brain, in particular the association of BCK to subcellular components as well as to specific, interacting proteins, overview
metabolism
co-localization and functional coupling of creatine kinase isoforms with ATP-producing and ATP-consuming reactions, a non-equilibrium state of the creatine kinase reaction, and restricted intracellular diffusion of adenine nucleotides support the concept of a cellular CK/PCr phosphoryl transfer network. The reactions catalyzed by different isoforms of compartmentalized creatine kinase, organized in intracellular energetic units tend to maintain the intracellular metabolic stability
metabolism
importance of functional coupling between MtCK, ANT and respiration/ATP synthesis provided by the close co-localization of MtCK and ANT in proteolipid complexes. Co-localization and functional coupling of creatine kinase isoforms with ATP-producing and ATP-consuming reactions, a non-equilibrium state of the creatine kinase reaction, and restricted intracellular diffusion of adenine nucleotides support the concept of a cellular CK/PCr phosphoryl transfer network. The reactions catalyzed by different isoforms of compartmentalized creatine kinase, organized in intracellular energetic units tend to maintain the intracellular metabolic stability
metabolism
the enzyme preferentially interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids, but not with polyunsaturated fatty acid-containing phosphatidic acids. Notably, the enzyme exclusively interacts with phosphatidic acid, whereas the protein does not bind to other lipids such as diacylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol (3,4,5)-triphosphate and cardiolipin
metabolism
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co-localization and functional coupling of creatine kinase isoforms with ATP-producing and ATP-consuming reactions, a non-equilibrium state of the creatine kinase reaction, and restricted intracellular diffusion of adenine nucleotides support the concept of a cellular CK/PCr phosphoryl transfer network. spatial organization of the CK/PCr shuttle in brain, in particular the association of BCK to subcellular components as well as to specific, interacting proteins, overview
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physiological function
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cerebral ischemia is accompanied by opposite changes in activities of mitochondrial creatine kinase (mCK) and cytoplasmic creatine kinase (cCK). Catalytic properties of mCK depend on the functional interaction with mitochondrial membranes. Acute ischemia impairs enzyme interaction with the mitochondrial membrane. These changes manifest in activation of mCK and change in the dimer/octamer ratio toward the formation of octamer. Mitochondrial creatine kinase gains new properties under conditions of oxygen eficiency in nerve cells
physiological function
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sarcomeric mitochondrial creatine kinase (sMiCK) interacts with NCX1IL (sodium-calcium exchanger). In addition to sMiCK, cytoplasmic muscle-type creatine kinase (CKM) is also able to interact with NCX1 in mammalian cells. Sarcomeric mitochondrial creatine kinase (sMiCK) and cytoplasmic muscle-type CK (CKM) are able to produce a recovery in the decreased NCX1 activity that is lost under energy-compromised conditions
physiological function
brain-type creatine kinase is an enzyme involved in energy homeostasis via the phosphocreatine-creatine kinase system, the CK system plays a critical role in energy homeostasis and ATP distribution
physiological function
brain-type creatine kinase is an enzyme involved in energy homeostasis via the phosphocreatine-creatine kinase system, the CK system plays a critical role in energy homeostasis and ATP distribution. Creatine kinase activity is critical for the beneficial effects of isozyme CKB of enhancing proteasome activity and reducing aggregate formation
physiological function
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creatine kinase catalyzes the reversible transfer of the phosphoryl group from phosphocreatine to ADP, regenerating ATP, and it is a major enzyme of higher eukaryotes that manages high, fluctuating energy demands to maintain cellular energy homeostasis and guarantee stable, locally buffered ATP/ADP ratios
physiological function
creatine kinase inhibits ADP-induced platelet aggregation. Inter-individual differences in plasma creatine kinase activity modulate the bleeding risk. Proposed mode of action of creatine kinase in main inhibitory pathways of platelet activation and the potential role of plasma creatine kinase herein, overview. The enzyme might attenuate platelet activation through scavenging plasma ADP as a binding protein, or via its catalytic activity converting ADP to ATP, leading to a reduced activation of the P2Y12 ADP receptor and attenuated platelet aggregation
physiological function
creatine kinase is a key player in maintaining cellular energy homeostasis using creatine for reversible phosphoryl transfer between ATP and phosphocreatine. The cellular energy sensor AMP-activated protein kinase (AMPK) is able to phosphorylate brain-type cratine kinase at Ser6 to trigger BCK localization at the endoplasmic reticulum, in close vicinity of the highly energy-demanding Ca2+ ATPase pump. Recruitment of BCK into the surface layer of a membrane, close to ATPases, and the resulting two-dimensional ATP diffusion along the membrane are sufficient to provide an energetic advantage. BCK may fuel the endoplasmic reticulum Ca2+ ATPase pump
physiological function
creatine kinase is a key player in maintaining cellular energy homeostasis using creatine for reversible phosphoryl transfer between ATP and phosphocreatine. The cellular energy sensor AMP-activated protein kinase (AMPK) is able to phosphorylate brain-type cratine kinase at serine 6 to trigger BCK localization at the endoplasmic reticulum, in close vicinity of the highly energy-demanding Ca2+ ATPase pump. Membrane localization of BCK seems to be an important and regulated feature for the fueling of membrane-located, ATP-dependent processes, stressing again the importance of local rather than global ATP concentrations. Creatine kinase microcompartments play a role in the energy metabolism. At the cellular level, creatine kinase acts mainly via two different mechanisms. Firstly, the enzyme enables the building-up of a global cellular energy buffer in the form of a large phosphocreatine pool that can be used to regenerate ATP during a temporal mismatch between ATP generation and consumption. Secondly, cytosolic and mitochondrial isozymes, together with highly concentrated and diffusible phosphocreatine, facilitate the so-called CK/PCr shuttle to correct for a spatial mismatch between ATP generation and -consumption within a cell. The CK/PCr shuttle is particularly important for large and polar cells with high and/or fluctuating energy demands such as skeletal and heart muscle cells, or many cell types in the brain, but may occur in any cell type expressing creatine kinase. BCK may fuel the endoplasmic reticulum Ca2+ ATPase pump. In retina photoreceptor cells, BCK may play an equally important role, but rather in synaptic transmission at the synaptic terminal or for cGMP resynthesis in the rod outer segments. In astrocytes and fibroblasts, BCK in peripheral cellular structures facilitates actin-driven cell spreading and migration
physiological function
creatine kinase is a key player in maintaining cellular energy homeostasis using creatine for reversible phosphoryl transfer between ATP and phosphocreatine. The cellular energy sensor AMP-activated protein kinase (AMPK) is able to phosphorylate brain-type cratine kinase at serine 6 to trigger BCK localization at the endoplasmic reticulum, in close vicinity of the highly energy-demanding Ca2+ ATPase pump. Membrane localization of BCK seems to be an important and regulated feature for the fueling of membrane-located, ATP-dependent processes, stressing again the importance of local rather than global ATP concentrations. Creatine kinase microcompartments play a role in the energy metabolism. At the cellular level, creatine kinase acts mainly via two different mechanisms. Firstly, the enzyme enables the building-up of a global cellular energy buffer in the form of a large phosphocreatine pool that can be used to regenerate ATP during a temporal mismatch between ATP generation and consumption. Secondly, cytosolic and mitochondrial isozymes, together with highly concentrated and diffusible phosphocreatine, facilitate the so-called CK/PCr shuttle to correct for a spatial mismatch between ATP generation and -consumption within a cell. The CK/PCr shuttle is particularly important for large and polar cells with high and/or fluctuating energy demands such as skeletal and heart muscle cells, or many cell types in the brain, but may occur in any cell type expressing creatine kinase. The role of MtCK within the mitochondrial interactosome is to separate energy fluxes from the intracellular energy signals and to amplify these signals due to the intramitochondrial recycling of ADP
physiological function
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the essential enzyme plays an important role in brain energy homeostasis
physiological function
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the enzyme plays an important role in brain energy homeostasis
physiological function
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brain-type creatine kinase is an enzyme involved in energy homeostasis via the phosphocreatine-creatine kinase system, the CK system plays a critical role in energy homeostasis and ATP distribution. Creatine kinase activity is critical for the beneficial effects of isozyme CKB of enhancing proteasome activity and reducing aggregate formation
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physiological function
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creatine kinase catalyzes the reversible transfer of the phosphoryl group from phosphocreatine to ADP, regenerating ATP, and it is a major enzyme of higher eukaryotes that manages high, fluctuating energy demands to maintain cellular energy homeostasis and guarantee stable, locally buffered ATP/ADP ratios
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physiological function
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creatine kinase is a key player in maintaining cellular energy homeostasis using creatine for reversible phosphoryl transfer between ATP and phosphocreatine. The cellular energy sensor AMP-activated protein kinase (AMPK) is able to phosphorylate brain-type cratine kinase at Ser6 to trigger BCK localization at the endoplasmic reticulum, in close vicinity of the highly energy-demanding Ca2+ ATPase pump. Recruitment of BCK into the surface layer of a membrane, close to ATPases, and the resulting two-dimensional ATP diffusion along the membrane are sufficient to provide an energetic advantage. BCK may fuel the endoplasmic reticulum Ca2+ ATPase pump
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additional information
dual active-site cysteine 283 residues
additional information
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dual active-site cysteine 283 residues
additional information
formation of the disulfide bond between the C74 and the C146 residues in the oxidized form
additional information
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formation of the disulfide bond between the C74 and the C146 residues in the oxidized form
additional information
phosphocreatine is an alternative energy carrier that compared to ATP is metabolically inert (except for the creatine kinase reaction), much smaller in molecular size and less charged over the physiological pH range, and is thus significantly more diffusible than ATP
additional information
phosphocreatine is an alternative energy carrier that compared to ATP is metabolically inert (except for the creatine kinase reaction), much smaller in molecular size and less charged over the physiological pH range, and is thus significantly more diffusible than ATP
additional information
phosphocreatine is an alternative energy carrier that compared to ATP is metabolically inert (except for the creatine kinase reaction), much smaller in molecular size and less charged over the physiological pH range, and is thus significantly more diffusible than ATP
additional information
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phosphocreatine is an alternative energy carrier that compared to ATP is metabolically inert (except for the creatine kinase reaction), much smaller in molecular size and less charged over the physiological pH range, and is thus significantly more diffusible than ATP
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