Crystal structure of human brain-type creatine kinase with ADP and creatine. PDB .
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
Creatine kinase (CK) — also known as creatine phosphokinase (CPK) or phospho-creatine kinase — is an enzyme (EC 220.127.116.11) expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.
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. Thus creatine kinase is an important enzyme in such tissues.
Clinically, creatine kinase is assayed in blood tests as a marker of myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy, the autoimmune myositides and in acute renal failure.
In the cells, the "cytosolic" CK enzymes consist of two subunits, which can be either B (brain type) or M (muscle type). There are, therefore, three different isoenzymes: CK-MM, CK-BB and CK-MB. The genes for these subunits are located on different chromosomes: B on 14q32 and M on 19q13. In addition to those three cytosolic CK isoforms, there are two mitochondrial creatine kinase isoenzymes, the ubiquitous and sarcomeric form. The functional entity of the latter two mitochondrial CK isoforms is an octamer consisting of four dimers each.
While mitochondrial creatine kinase is directly involved in formation of phospho-creatine from mitochondrial ATP, cytosolic CK regenerates ATP from ADP, using PCr. This happens at intracellular sites where ATP is used in the cell, with CK acting as an in situ ATP regenerator.
|CKB||creatine kinase, brain, BB-CK|
|CKBE||creatine kinase, ectopic expression|
|CKM||creatine kinase, muscle, MM-CK|
|CKMT1A, CKMT1B||creatine kinase mitochondrial 1; ubiquitous mtCK; or umtCK|
|CKMT2||creatine kinase mitochondrial 2; sarcomeric mtCK; or smtCK|
Isoenzyme patterns differ in tissues. CK-BB is expressed in all tissues at low levels and has little clinical relevance. Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%). The myocardium (heart muscle), in contrast, expresses CK-MM at 70% and CK-MB at 25–30%.
The mitochondrial creatine kinase (CKm) 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).
CK is often determined routinely in a medical laboratory. It is also determined specifically in patients with chest pain or if acute renal failure is suspected. Normal values are usually between 60 and 174 IU/L, where one unit is enzyme activity, more specifically the amount of enzyme that will catalyze 1 μmol of substrate per minute under specified conditions (temperature, pH, substrate concentrations and activators.) This test is not specific for the type of CK that is elevated.
Elevation of CK is an indication of damage to muscle. It is therefore indicative of injury, rhabdomyolysis, myocardial infarction, myositis and myocarditis. The use of statin medications, which are commonly used to decrease serum cholesterol levels, may be associated with elevation of the CPK level in about 1% of the patients taking these medications, and with actual muscle damage in a much smaller proportion.
There is an inverse relationship in the serum levels of T3 and CK in thyroid disease. In hypothyroid patients, with decrease in serum T3 there is a significant increase in CK. Therefore, the estimation of serum CK is considered valuable in screening for hypothyroid patients.
Isoenzyme determination has been used extensively as an indication for myocardial damage in heart attacks. Troponin measurement has largely replaced this in many hospitals, although some centers still rely on CK-MB.
CK can be used in the diagnosis of neuroleptic malignant syndrome, which is manifested as fever, rigidity, altered mental state and autonomic dysfunction.
- Bong, S.; Moon, J.; Nam, K.; Lee, K.; Chi, Y.; Hwang, K. (2008). "Structural studies of human brain-type creatine kinase complexed with the ADP–Mg2+–NO3−–creatine transition-state analogue complex". FEBS Letters 582 (28): 3959–3965. doi:10.1016/j.febslet.2008.10.039. PMID 18977227.
- Wallimann T; Wyss M; Brdiczka D; Nicolay K; Eppenberger HM (January 1992). "Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the "phosphocreatine circuit" for cellular energy homeostasis". The Biochemical Journal 281 (1): 21–40. PMC 1130636. PMID 1731757.
- Wallimann T; Hemmer W (1994). "Creatine kinase in non-muscle tissues and cells". Molecular and Cellular Biochemistry. 133–135: 193–220. doi:10.1007/BF01267955. PMID 7808454.
- Schlattner U; Tokarska-Schlattner M; Wallimann T (February 2006). "Mitochondrial creatine kinase in human health and disease". Biochimica et Biophysica Acta 1762 (2): 164–80. doi:10.1016/j.bbadis.2005.09.004. PMID 16236486.
- Armstrong, April W.; David E. Golan (2008). "Pharmacology of Hemostasis and Thrombosis". In David E. Golan, Armen H. Tashjian, Ehrin J. Armstrong and April W. Armstrong. Principles of pharmacology: the pathophysiologic basis of drug therapy. Philadelphia: Lippincott Williams & Wilkins. p. 388. ISBN 978-0-7817-8355-2. OCLC 76262148.
- Michael L. Bishop, Edward P. Fody and Larry E. Schoeff, ed. (2004). Clinical chemistry: principles, procedures, correlations. Philadelphia: Lippincott Williams & Wilkins. p. 243. ISBN 978-0-7817-4611-3. OCLC 56446391.
- Hekimsoy, Zeliha; Oktem, Iris Kavalali (2005). "Serum creatine kinase levels in overt and subclinical hypothyroidism". Endocrine Research 31 (3): 171–5. doi:10.1080/07435800500371706. PMID 16392619.
- Simply stated at mdausa.org
- Creatine Kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
- CPK isoenzymes test MedlinePlus Encyclopedia 003504
- CK at Lab Tests Online