Creatine kinase

Creatine Kinase

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Creatine kinase (CK), also known as phosphocreatine kinase or creatine phosphokinase (CPK) is an enzyme (EC 2.7.3.2) expressed by various tissue types. It catalyses the conversion of creatine to phosphocreatine, consuming adenosine triphosphate (ATP) and generating adenosine diphosphate (ADP).

In tissues that consume ATP rapidly, especially skeletal muscle, but also brain and smooth muscle, phosphocreatine serves as an energy reservoir for the rapid regeneration of ATP. 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 and in acute renal failure.

There are three different isoenzymes that come from three distinct locations in the body:

• BB: Brain, prostate, gastrointestinal, breast, ovary, lung
• MM: Skeletal muscle
• MB: Heart

Types

In most of the cell, the CK enzyme consists 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, there are two mitochondrial creatine kinases, the ubiquitous and sarcomeric form.

creatine kinase, brain
Identifiers
Symbol	CKB
Alt. symbols	CKBB, CK-1
Entrez	1152
HUGO	1991
OMIM	123280
RefSeq	NM_001823
UniProt	P12277
Other data
EC number	2.7.3.2
Locus	Chr. 14 q32.3

creatine kinase, muscle
File:Creatine kinase.PNG
Identifiers
Symbol	CKM
Alt. symbols	CKMM, CK-3
Entrez	1158
HUGO	1994
OMIM	123310
RefSeq	NM_001824
UniProt	P06732
Other data
EC number	2.7.3.2
Locus	Chr. 19 q13.2-13.3

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Most recent articles on Creatine kinase Most cited articles on Creatine kinase Review articles on Creatine kinase Articles on Creatine kinase in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Creatine kinase Images of Creatine kinase Photos of Creatine kinase Podcasts & MP3s on Creatine kinase Videos on Creatine kinase
Evidence Based Medicine
Cochrane Collaboration on Creatine kinase Bandolier on Creatine kinase TRIP on Creatine kinase
Clinical Trials
Ongoing Trials on Creatine kinase at Clinical Trials.gov Trial results on Creatine kinase Clinical Trials on Creatine kinase at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Creatine kinase NICE Guidance on Creatine kinase NHS PRODIGY Guidance FDA on Creatine kinase CDC on Creatine kinase
Books
Books on Creatine kinase
News
Creatine kinase in the news Be alerted to news on Creatine kinase News trends on Creatine kinase
Commentary
Blogs on Creatine kinase
Definitions
Definitions of Creatine kinase
Patient Resources / Community
Patient resources on Creatine kinase Discussion groups on Creatine kinase Patient Handouts on Creatine kinase Directions to Hospitals Treating Creatine kinase Risk calculators and risk factors for Creatine kinase
Healthcare Provider Resources
Symptoms of Creatine kinase Causes & Risk Factors for Creatine kinase Diagnostic studies for Creatine kinase Treatment of Creatine kinase
Continuing Medical Education (CME)
CME Programs on Creatine kinase
International
Creatine kinase en Espanol Creatine kinase en Francais
Business
Creatine kinase in the Marketplace Patents on Creatine kinase
Experimental / Informatics
List of terms related to Creatine kinase

Isoenzyme patterns differ in tissues. CK-BB occurs mainly in tissues, and its levels do rarely have any significance in bloodstream. 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 expressed in all tissues at low levels and has little clinical relevance.

The mitochondrial creatine kinase (CK_m), which produces ATP from ADP by converting creatine phosphate to creatine, is present between the two membranes of the mitochondrion. Apart from the mitochondrial form, there are three forms present in the cytosol—CK_a (in times of acute need, produces ATP in the cytosol at the cost of creatine phosphate), CK_c (maintains critical concentration of creatine and creatine phosphate in the cytosol by coupling their phosphorylation and dephosphorylation respectively with ATP and ADP) and CK_g (which couples direct phosphorylation of creatine to the glycolytic pathway (see glycolysis).

Laboratory testing

CK is often determined routinely in emergency patients. In addition, it is determined specifically in patients with chest pain and acute renal failure is suspected. Normal values are usually between 25 and 200 U/L. 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, muscular dystrophy, myositis, myocarditis, malignant hyperthermia and neuroleptic malignant syndrome. It is also seen in McLeod syndrome and hypothyroidism. 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.

Lowered CK can be an indication of alcoholic liver disease and rheumatoid arthritis.

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.

Differential Diagnosis

Differential Diagnosis of Increased Total CK

• Alcoholism
• Arterial embolism
• Asenapine maleate
• Bacterial myositis
• Becker's Muscular Dystrophy
• Crush injury or trauma
• Duchenne's Muscular Dystrophy
• Hyperthermia
• Hyperthyroidism
• Hypothyroidism
• Intramuscular injections
• Lymphangitis
• Leyden-Moebius Muscular Dystrophy
• Liver, pancreas and gastrointestinal diseases
• Medications such as Saxagliptin
• Muscular spasm
• Myasthenia Gravis
• Myositis
• Neurogenic muscular atrophy
• Pancreatic cancer
• Polymyositis
• Pralidoxime
• Pregnancy and labor
• Rhabdomyolysis
• Seizure
• Surgery
• Thyrotoxicosis
• Vigorous exercise
• Viral myositis

Differential Diagnosis of Increased Total CK and CK-MB Ratio

• Cardiac contusion
• Cardiogenic shock
• Heart surgery
• Myocardial Infarction
• Perimyocarditis
• Right ventricular failure

CK and CK-MB Elevation During Pregnancy

• In contrast to troponin, the utility of CK-MB for the diagnosis of AMI in pregnancy has not been validated.
• During labor and within 30 minutes of delivery, there may be up to two-fold increase in CK and CK-MB concentrations.
• Concentrations increase within 30 minutes of delivery and peak at 24 hours post-delivery.
• It is thought that both the cells in the uterus and the placenta may leak enzymes.
• To view changes in troponin concentration during pregnancy, click here.

See also

• reference ranges for common blood tests
• kinase

References

• Simply stated at mdausa.org
• Creatine+Kinase at the US National Library of Medicine Medical Subject Headings (MeSH)