Creatine Kinase (肌酸激酶)

Creatine Kinase (CK) is an enzyme that catalyzes the reversible reaction between creatine and ATP and belongs to the guanidine phosphokinase family. This family is highly conserved in the animal kingdom, and its members also include arginine kinase, guanidine acetate kinase, etc. There are four main isoenzymes of CK, which are divided into two cytoplasmic types (MM-CK and BB-CK, which can form MB heterodimers) and two mitochondrial types (the ubiquitous Mi₋CK and the sarcomeric Mi-CK). CK has multiple upstream and downstream or interaction targets in the cell. In the energy metabolism pathway, CK in mitochondria interacts closely with adenine nucleotide translocase (ANT) and participates in the regulation of mitochondrial respiration; some cytoplasmic CKs bind to glycolytic enzyme complexes, such as pyruvate kinase, phosphofructokinase, etc., affecting the glycolysis process. In terms of muscle contraction, CK interacts with myosin ATPase, Ca²⁺-ATPase of sarcoplasmic reticulum, Na⁺-K⁺-ATPase of sarcolemma, etc., to provide energy support for muscle contraction and relaxation. In addition, CK also interacts with proteins related to cell cycle regulation. For example, in cell cycle regulation, CK works synergistically with AK, NDPK, etc. The main function of CK is to maintain the energy homeostasis of cells. In cells with high and fluctuating energy demands, such as muscle and brain cells, CK converts ATP into PCr to store energy at ATP generation sites through the creatine phosphate-creatine (PCr-Cr) shuttle mechanism, and converts PCr into ATP at ATP consumption sites, thereby effectively buffering the fluctuation of ATP levels in cells and ensuring the stability of cellular energy supply. At the same time, CK is also involved in the regulation of cell metabolism, affecting the progress of related metabolic reactions by regulating the ATP/ADP ratio, and plays a key role in intracellular energy transport, connecting ATP generation processes such as glycolysis and mitochondrial oxidative phosphorylation with many intracellular ATP consumption processes. CK is closely related to many diseases. In myocardial and skeletal muscle diseases, it is an important diagnostic indicator. For example, in acute myocardial infarction, the CK level in serum will increase significantly, especially the CK-MB isoenzyme, which can assist in judging myocardial damage. In muscle diseases such as Duchenne muscular dystrophy, the patient's serum CK activity is significantly increased. In terms of nervous system diseases, the lack of brain-type CK can lead to behavioral changes, spatial learning and memory dysfunction and other problems. In addition, CK also plays an important role in the occurrence and development of cancer. It participates in the energy metabolism, cell cycle regulation and cell migration of cancer cells. Abnormal CK levels are associated with a variety of cancers, such as ovarian cancer and breast cancer, and are expected to become a biomarker and therapeutic target for cancer diagnosis^{[1][2][3][4][5][6][7][8]}.