Creatine Kinase - Functions

Functions

The mitochondrial creatine kinase (CK_m) is present in the mitochondrial intermembrane space, where it produces phosphocreatine (PCr) from mitochondrially-generated ATP and creatine (Cr) imported from the cytosol. 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. 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. Mitochondrial mtCK and cytosolic CK are connected in a so-called PCr/Cr-shuttle or circuit. PCr generated by mtCK in mitochondria is shuttled to cytosolic CK that is coupled to ATP-dependent processes, e.g. ATPases, like acto-myosin ATPase for muscle contraction, or ion pumps, like the calcium pump for muscle relaxation. There, the bound cytosolic CK accepts the PCr shuttled through the cell and uses it to regenerate ATP, which can then be used as energy source by the ATPases. (CK is associated intimately with the ATPases, forming a functionally coupled microcompartment.) Thus, 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).