Thus, CK enhances skeletal, cardiac, and smooth muscle contractility, and is involved in the generation of blood pressure. PCr is not only an energy buffer, but also a cellular transport form of energy between subcellular sites of energy (ATP) production (mitochondria and glycolysis) and those of energy utilization (ATPases). The bound cytosolic CK accepts the PCr shuttled through the cell and uses ADP to regenerate ATP, which can then be used as an energy source by the ATPases (CK is associated intimately with the ATPases, forming a functionally coupled microcompartment). ATPases, such as acto-myosin ATPase and calcium ATPase involved in muscle contraction, and sodium/potassium ATPase involved in sodium retention in the kidney. PCr generated by mtCK in mitochondria is shuttled to cytosolic CK that is coupled to ATP-dependent processes, e.g. Mitochondrial mtCK and cytosolic CK are connected in a so-called PCr/Cr-shuttle or circuit. Whereas MM-CK is expressed in sarcomeric muscle, that is, skeletal and cardiac muscle, MB-CK is expressed in cardiac muscle, and BB-CK is expressed in smooth muscle and in most non-muscle tissues. Apart from the two mitochondrial CK isoenzyme forms, that is, ubiquitous mtCK (present in non-muscle tissues) and sarcomeric mtCK (present in sarcomeric muscle), there are three cytosolic CK isoforms present in the cytosol, depending on the tissue. Mitochondrial creatine kinase (CK m) is present in the mitochondrial intermembrane space, where it regenerates phosphocreatine (PCr) from mitochondrially generated ATP and creatine (Cr) imported from the cytosol. Cytosolic BB-CK, as well as muscle-type MM-CK both form banana-shaped symmetric dimers, with one catalytic active site in each subunit. The atomic structure of the banana-shaped, dimeric cytosolic brain-type BB-CK was solved in 1999 at a resolution of 1,4 Å. Both mt-CK isoforms form octameric structures (built of 4 banana-like dimers) with a four-fold symmetry and a central channel. The first structure of a creatine kinase solved by X-ray protein crystallography was that of the octameric, sarcomeric muscle-type mitochondrial CK (s-mtCK) in 1996., followed by the structure of ubiquitous mitochondrial CK (u-mtCK) in 2000. CK-BB is predominantly expressed in brain and smooth muscle, including vascular and uterine tissue. The myocardium (heart muscle), in contrast, expresses CK-MM at 70% and CK-MB at 25–30%. Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%). This happens at intracellular sites where ATP is used in the cell, with CK acting as an in situ ATP regenerator.Ĭreatine kinase mitochondrial 1 ubiquitous mtCK or umtCKĬreatine kinase mitochondrial 2 sarcomeric mtCK or smtCK While mitochondrial creatine kinase is directly involved in the formation of phosphocreatine from mitochondrial ATP, cytosolic CK regenerates ATP from ADP, using PCr. The functional entity of the mitochondrial CK isoforms is an octamer consisting of four dimers each. In addition to those three cytosolic CK isoforms, there are two mitochondrial creatine kinase isoenzymes, the ubiquitous form and the sarcomeric form. The genes for these subunits are located on different chromosomes: B on 14q32 and M on 19q13. There are, therefore, three different isoenzymes: CK-MM, CK-BB and CK-MB. In the cells, the cytosolic CK enzymes consist of two subunits, which can be either B (brain type) or M (muscle type). Ĭlinically, creatine kinase is assayed in blood tests as a marker of damage of CK-rich tissue such as in myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy, autoimmune myositides, and acute kidney injury. Thus creatine kinase is an important enzyme in such tissues. In tissues and cells that consume ATP rapidly, especially skeletal muscle, but also brain, photoreceptor cells of the retina, hair cells of the inner ear, spermatozoa and smooth muscle, PCr serves as an energy reservoir for the rapid buffering and regeneration of ATP in situ, as well as for intracellular energy transport by the PCr shuttle or circuit. This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). Ĭreatine kinase ( CK), also known as creatine phosphokinase ( CPK) or phosphocreatine kinase, is an enzyme ( EC 2.7.3.2) expressed by various tissues and cell types. Crystal structure of human brain-type creatine kinase with ADP and creatine.
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