| Creatine kinase |
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Crystal structure of human brain-type creatine kinase with ADP and creatine. PDB 3b6r.[1]
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| Identifiers |
| EC number |
2.7.3.2 |
| CAS number |
9001-15-4 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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Creatine kinase (CK) — also known as creatine phosphokinase (CPK) or phospho-creatine kinase — is an enzyme (EC 2.7.3.2) expressed by various tissues and cell types. CK catalyses the conversion of creatine and utilizes 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.[2] Thus creatine kinase is an important enzyme in such tissues.[3]
Clinically, 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, the autoimmune myositides and in acute renal failure.
Contents
- 1 Types
- 2 Functions
- 3 Laboratory testing
- 4 See also
- 5 References
- 6 External links
Types
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.[4]
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.
| gene |
protein |
| 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. 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%. CK-BB is predominantly expressed in brain and smooth muscle, including vascular and uterine tissue.
Functions
The mitochondrial creatine kinase (CKm) is present in the mitochondrial intermembrane space, where it regenerates 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, such as acto-myosin ATPase and calcium ATPase involved in muscle contraction, and sodium/potassium ATPase involved in sodium retention in the kidney. The bound cytosolic CK accepts the PCr shuttled through the cell and uses ADP 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). 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).[2] Thus, CK enhances skeletal, cardiac, and smooth muscle contractility, and is involved in the generation of blood pressure.[5]
Laboratory testing
CK is often determined routinely in a medical laboratory. It used to be determined specifically in patients with chest pain but this test has been replaced by troponin. Normal values at rest are usually between 60 and 174 IU/L,[6] 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.[7]) This test is not specific for the type of CK that is elevated.
Creatine kinase in the blood may be high in health and disease. Exercise increases the outflow of creatine kinase to the blood stream for up to a week, and this is the most common cause of high CK in blood.[8] Furthermore, high CK in the blood may be related to high intracellular CK such as in persons of African descent.[9] Finally, high CK in the blood may be an indication of damage to CK-rich tissue, such as in rhabdomyolysis, myocardial infarction, myositis and myocarditis. This means creatine kinase in blood may be elevated in a wide range of clinical conditions including the use of medication such as statins; endocrine disorders such as hypothyroidism;[10] and skeletal muscle diseases and disorders including malignant hyperthermia,[11] and neuroleptic malignant syndrome.[12]
Furthermore, the 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.
Reference ranges for blood tests, comparing blood content of creatine kinase (shown in yellow near center) with other constituents.
See also
- Kinase
- Reference ranges for blood tests
References
- ^ 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.
- ^ a b 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. doi:10.1042/bj2810021. 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.
- ^ Brewster, L. M.; Mairuhu, G; Bindraban, N. R.; Koopmans, R. P.; Clark, J. F.; Van Montfrans, G. A. (2006). "Creatine kinase activity is associated with blood pressure". Circulation 114 (19): 2034–9. doi:10.1161/CIRCULATIONAHA.105.584490. PMID 17075013.
- ^ 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.
- ^ >Johnsen SH, Wilsgaard T, Bekkelund SI (January 2011). "Creatine kinase activity and blood pressure in a normal population: the Tromsø study". Journal of Hypertension 29 (1): 36–42. doi:10.1097/HJH.0b013e32834068e0. PMID 21063205.
- ^ Brewster LM, Coronel CM, Sluiter W (March 2012). "Ethnic differences in tissue creatine kinase activity: an observational study". PLOS ONE 7 (3): e32471. doi:10.1371/journal.pone.0032471. PMID 22438879.
- ^ Hekimsoy, Z; Oktem, I. K. (2005). "Serum creatine kinase levels in overt and subclinical hypothyroidism". Endocrine research 31 (3): 171–5. doi:10.1080/07435800500371706. PMID 16392619.
- ^ Johannsen, S; Berberich, C; Metterlein, T; Roth, C; Reiners, K; Roewer, N; Schuster, F (2013). "Screening test for malignant hyperthermia in patients with persistent hyperCKemia: A pilot study". Muscle & Nerve 47 (5): 677–81. doi:10.1002/mus.23633. PMID 23400941.
- ^ O'Dwyer, A. M.; Sheppard, N. P. (1993). "The role of creatine kinase in the diagnosis of neuroleptic malignant syndrome". Psychological Medicine 23 (2): 323–6. doi:10.1017/s0033291700028415. PMID 8101383.
External links
- 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
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Mitochondrial proteins
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| Outer membrane |
| fatty acid degradation |
- Carnitine palmitoyltransferase I
- Long-chain-fatty-acid—CoA ligase
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| tryptophan metabolism |
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monoamine neurotransmitter
metabolism |
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| Intermembrane space |
- Adenylate kinase
- Creatine kinase
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| Inner membrane |
| oxidative phosphorylation |
- Coenzyme Q – cytochrome c reductase
- Cytochrome c
- NADH dehydrogenase
- Succinate dehydrogenase
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| pyrimidine metabolism |
- Dihydroorotate dehydrogenase
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| mitochondrial shuttle |
- Malate-aspartate shuttle
- Glycerol phosphate shuttle
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| other |
- Glutamate aspartate transporter
- Glycerol-3-phosphate dehydrogenase
- ATP synthase
- Carnitine palmitoyltransferase II
- Uncoupling protein
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| Matrix |
| citric acid cycle |
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- Oxoglutarate dehydrogenase complex
- Succinyl coenzyme A synthetase
- Fumarase
- Malate dehydrogenase
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| anaplerotic reactions |
- Aspartate transaminase
- Glutamate dehydrogenase
- Pyruvate dehydrogenase complex
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| urea cycle |
- Carbamoyl phosphate synthetase I
- Ornithine transcarbamylase
- N-Acetylglutamate synthase
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| alcohol metabolism |
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| Other/to be sorted |
| steroidogenesis |
- Cholesterol side-chain cleavage enzyme
- Steroid 11-beta-hydroxylase
- Aldosterone synthase
- Frataxin
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- Mitochondrial membrane transport protein
- Mitochondrial permeability transition pore
- Mitochondrial carrier
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| Mitochondrial DNA |
| Complex I |
- MT-ND1
- MT-ND2
- MT-ND3
- MT-ND4
- MT-ND4L
- MT-ND5
- MT-ND6
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| Complex III |
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| Complex IV |
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| ATP synthase |
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| tRNA |
- MT-TA
- MT-TC
- MT-TD
- MT-TE
- MT-TF
- MT-TG
- MT-TH
- MT-TI
- MT-TK
- MT-TL1
- MT-TL2
- MT-TM
- MT-TN
- MT-TP
- MT-TQ
- MT-TR
- MT-TS1
- MT-TS2
- MT-TT
- MT-TV
- MT-TW
- MT-TY
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see also mitochondrial diseases
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Metabolism: Protein metabolism, synthesis and catabolism enzymes
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Essential amino acids are in Capitals
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| K→acetyl-CoA |
| LYSINE→ |
- Saccharopine dehydrogenase
- Glutaryl-CoA dehydrogenase
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| LEUCINE→ |
- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- Isovaleryl coenzyme A dehydrogenase
- Methylcrotonyl-CoA carboxylase
- Methylglutaconyl-CoA hydratase
- 3-hydroxy-3-methylglutaryl-CoA lyase
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| TRYPTOPHAN→ |
- Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase
- Arylformamidase
- Kynureninase
- 3-hydroxyanthranilate oxidase
- Aminocarboxymuconate-semialdehyde decarboxylase
- Aminomuconate-semialdehyde dehydrogenase
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| PHENYLALANINE→tyrosine→ |
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| G |
G→pyruvate
→citrate |
| glycine→serine→ |
- Serine hydroxymethyltransferase
- Serine dehydratase
- glycine→creatine: Guanidinoacetate N-methyltransferase
- Creatine kinase
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| alanine→ |
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| cysteine→ |
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| threonine→ |
- L-threonine dehydrogenase
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G→glutamate→
α-ketoglutarate |
| HISTIDINE→ |
- Histidine ammonia-lyase
- Urocanate hydratase
- Formiminotransferase cyclodeaminase
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| proline→ |
- Proline oxidase
- Pyrroline-5-carboxylate reductase
- 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1
- PYCR1
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| arginine→ |
- Ornithine aminotransferase
- Ornithine decarboxylase
- Agmatinase
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| →alpha-ketoglutarate→TCA |
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| Other |
- cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase
- Glutathione synthetase
- Gamma-glutamyl transpeptidase
- glutamate→glutamine: Glutamine synthetase
- Glutaminase
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G→propionyl-CoA→
succinyl-CoA |
| VALINE→ |
- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- Enoyl-CoA hydratase
- 3-hydroxyisobutyryl-CoA hydrolase
- 3-hydroxyisobutyrate dehydrogenase
- Methylmalonate semialdehyde dehydrogenase
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| ISOLEUCINE→ |
- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
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| METHIONINE→ |
- generation of homocysteine: Methionine adenosyltransferase
- Adenosylhomocysteinase
- regeneration of methionine: Methionine synthase/Homocysteine methyltransferase
- Betaine-homocysteine methyltransferase
- conversion to cysteine: Cystathionine beta synthase
- Cystathionine gamma-lyase
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| THREONINE→ |
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| →succinyl-CoA→TCA |
- Propionyl-CoA carboxylase
- Methylmalonyl CoA epimerase
- Methylmalonyl-CoA mutase
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| G→fumarate |
| PHENYLALANINE→tyrosine→ |
- Phenylalanine hydroxylase
- Tyrosine aminotransferase
- 4-Hydroxyphenylpyruvate dioxygenase
- Homogentisate 1,2-dioxygenase
- Fumarylacetoacetate hydrolase
- tyrosine→melanin: Tyrosinase
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| G→oxaloacetate |
| asparagine→aspartate→ |
- Asparaginase/Asparagine synthetase
- Aspartate transaminase
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References ranges for blood tests (CPT 82000–84999)
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| Electrolytes |
- Sodium
- Potassium
- Chloride
- Calcium
- Renal function
- Creatinine
- Urea
- BUN-to-creatinine ratio
- Plasma osmolality
- Serum osmolal gap
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| Acid-base |
- Anion gap
- Arterial blood gas
- Base excess
- Bicarbonate
- CO2 content
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| Iron tests |
- Ferritin
- Serum iron
- Transferrin saturation
- Total iron-binding capacity
- Transferrin
- Transferrin receptor
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| Hormones |
- ACTH stimulation test
- Thyroid function tests
- Thyroid-stimulating hormone
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| Metabolism |
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| Cardiovascular |
- Cardiac marker
- CPK-MB test
- Lactate dehydrogenase
- Myoglobin
- Glycogen phosphorylase isoenzyme BB
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| Liver function tests |
- Proteins
- Human serum albumin
- Serum total protein
- ALP
- transaminases
- Bilirubin
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| Pancreas |
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Transferases: phosphorus-containing groups (EC 2.7)
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2.7.1-2.7.4:
phosphotransferase/kinase
(PO4) |
| 2.7.1: OH acceptor |
- Hexo-
- Gluco-
- Fructo-
- Galacto-
- Phosphofructo-
- 1
- Liver
- Muscle
- Platelet
- 2
- Riboflavin
- Shikimate
- Thymidine
- NAD+
- Glycerol
- Pantothenate
- Mevalonate
- Pyruvate
- Deoxycytidine
- PFP
- Diacylglycerol
- Phosphoinositide 3
- Class I PI 3
- Class II PI 3
- Sphingosine
- Glucose-1,6-bisphosphate synthase
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| 2.7.2: COOH acceptor |
- Phosphoglycerate
- Aspartate kinase
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| 2.7.3: N acceptor |
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| 2.7.4: PO4 acceptor |
- Phosphomevalonate
- Adenylate
- Nucleoside-diphosphate
- Uridylate
- Guanylate
- Thiamine-diphosphate
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2.7.6: diphosphotransferase
(P2O7) |
- Ribose-phosphate diphosphokinase
- Thiamine diphosphokinase
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2.7.7: nucleotidyltransferase
(PO4-nucleoside) |
| Polymerase |
| DNA polymerase |
- DNA-directed DNA polymerase
- I
- II
- III
- IV
- V
- RNA-directed DNA polymerase
- Reverse transcriptase
- Telomerase
- DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase
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| RNA nucleotidyltransferase |
- RNA polymerase/DNA-directed RNA polymerase
- RNA polymerase I
- RNA polymerase II
- RNA polymerase III
- RNA polymerase IV
- Primase
- RNA-dependent RNA polymerase
- PNPase
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Phosphorolytic
3' to 5' exoribonuclease |
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| Nucleotidyltransferase |
- UTP—glucose-1-phosphate uridylyltransferase
- Galactose-1-phosphate uridylyltransferase
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| Guanylyltransferase |
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| Other |
- Recombinase (Integrase)
- Transposase
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| 2.7.8: miscellaneous |
| Phosphatidyltransferases |
- CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase
- CDP-diacylglycerol—serine O-phosphatidyltransferase
- CDP-diacylglycerol—inositol 3-phosphatidyltransferase
- CDP-diacylglycerol—choline O-phosphatidyltransferase
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| Glycosyl-1-phosphotransferase |
- N-acetylglucosamine-1-phosphate transferase
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2.7.10-2.7.13: protein kinase
(PO4; protein acceptor) |
| 2.7.10: protein-tyrosine |
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| 2.7.11: protein-serine/threonine |
- see serine/threonine-specific protein kinases
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| 2.7.12: protein-dual-specificity |
- see serine/threonine-specific protein kinases
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| 2.7.13: protein-histidine |
- Protein-histidine pros-kinase
- Protein-histidine tele-kinase
- Histidine kinase
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Proteins: enzymes
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| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
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