Creatine Kinase

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

## Contents

* 1 Overview
* 2 Types
* 3 Laboratory testing
* 4 Differential Diagnosis
* 4.1 Differential Diagnosis of Increased Total CK
* 5 Differential Diagnosis of Increased Total CK and CK-MB Ratio
* 6 CK and CK-MB Elevation During Pregnancy
* 7 See also
* 8 References

## Overview

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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

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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

Template:Protbox finish

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Media

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Clinical Trials

Ongoing Trials on Creatine kinase at Clinical Trials.gov

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NICE Guidance on Creatine kinase

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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 (CKm), 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—CKa (in times of acute need, produces ATP in the cytosol at the cost of creatine phosphate), CKc (maintains critical concentration of creatine and creatine phosphate in the cytosol by coupling their phosphorylation and dephosphorylation respectively with ATP and ADP) and CKg (which couples direct phosphorylation of creatine to the glycolytic pathway (see glycolysis).

## Laboratory testing

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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

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### Differential Diagnosis of Increased Total CK

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* 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

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

## CK and CK-MB Elevation During Pregnancy

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* In contrast to troponin, the utility of CK-MB for the diagnosis of AMI in pregnancy has not been validated.[1]
* During labor and within 30 minutes of delivery, there may be up to two-fold increase in CK and CK-MB concentrations.[2][1]
* Concentrations increase within 30 minutes of delivery and peak at 24 hours post-delivery.[2][1]
* It is thought that both the cells in the uterus and the placenta may leak enzymes.[2][1]
* To view changes in troponin concentration during pregnancy, click here.

## See also

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* reference ranges for common blood tests
* kinase

## References

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

* v
* t
* e

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO4)|

| 2.7.1: OH acceptor|

* Hexo-
* Gluco-
* Fructo-
* Hepatic
* Galacto-
* Phosphofructo-
* 1
* Liver
* Muscle
* Platelet
* 2
* Riboflavin
* Shikimate
* Thymidine
* ADP-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

|

2.7.2: COOH acceptor|

* Phosphoglycerate
* Aspartate kinase

2.7.3: N acceptor|

* Creatine

2.7.4: PO4 acceptor|

* Phosphomevalonate
* Adenylate
* Nucleoside-diphosphate
* Uridylate
* Guanylate
* Thiamine-diphosphate

2.7.6: diphosphotransferase
(P2O7)|

* Ribose-phosphate diphosphokinase
* Thiamine diphosphokinase

2.7.7: nucleotidyltransferase
(PO4-nucleoside)|

| Polymerase|

| DNA polymerase|

DNA-directed DNA polymerase

III

RNA-directed DNA polymerase
Reverse transcriptase

Telomerase

DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

|

RNA nucleotidyltransferase|

RNA polymerase/DNA-directed RNA polymerase
RNA polymerase I

III

Primase
RNA-dependent RNA polymerase

PNPase

Phosphorolytic
3' to 5' exoribonuclease|

* RNase PH
* PNPase

Nucleotidyltransferase|

* UTP—glucose-1-phosphate uridylyltransferase
* Galactose-1-phosphate uridylyltransferase

Guanylyltransferase|

* mRNA capping enzyme

Other|

* Recombinase (Integrase)
* Transposase

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

|

Glycosyl-1-phosphotransferase|

* N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO4; protein acceptor)|

| 2.7.10: protein-tyrosine|

* see tyrosine kinases

|

2.7.11: protein-serine/threonine|

* see serine/threonine-specific protein kinases

2.7.12: protein-dual-specificity|

* see serine/threonine-specific protein kinases

2.7.13: protein-histidine|

* Protein-histidine pros-kinase
* Protein-histidine tele-kinase
* Histidine kinase

* v
* t
* e

Mitochondrial proteins

Outer membrane|

| fatty acid degradation|

* Carnitine palmitoyltransferase I
* Long-chain-fatty-acid—CoA ligase

|

tryptophan metabolism|

* Kynureninase

monoamine neurotransmitter
metabolism|

* Monoamine oxidase

Intermembrane space|

* Adenylate kinase
* Creatine kinase

Inner membrane|

| oxidative phosphorylation|

* Coenzyme Q – cytochrome c reductase
* Cytochrome c
* NADH dehydrogenase
* Succinate dehydrogenase

|

pyrimidine metabolism|

* Dihydroorotate dehydrogenase

mitochondrial shuttle|

* Malate-aspartate shuttle
* Glycerol phosphate shuttle

other|

* Glutamate aspartate transporter
* Glycerol-3-phosphate dehydrogenase
* ATP synthase
* Carnitine palmitoyltransferase II
* Uncoupling protein

Matrix|

| citric acid cycle|

* Citrate synthase
* Aconitase
* Isocitrate dehydrogenase
* Oxoglutarate dehydrogenase complex
* Succinyl coenzyme A synthetase
* Fumarase
* Malate dehydrogenase

|

anaplerotic reactions|

* Aspartate transaminase
* Glutamate dehydrogenase
* Pyruvate dehydrogenase complex

urea cycle|

* Carbamoyl phosphate synthetase I
* Ornithine transcarbamylase
* N-Acetylglutamate synthase

alcohol metabolism|

* ALDH2

* PMPCB

Other/to be sorted|

| steroidogenesis|

* Cholesterol side-chain cleavage enzyme
* Steroid 11-beta-hydroxylase
* Aldosterone synthase
* Frataxin

|

* Mitochondrial membrane transport protein
* Mitochondrial permeability transition pore
* Mitochondrial carrier

Mitochondrial DNA|

| Complex I|

* MT-ND1
* MT-ND2
* MT-ND3
* MT-ND4
* MT-ND4L
* MT-ND5
* MT-ND6

|

Complex III|

* MT-CYB

Complex IV|

* MT-CO1
* MT-CO2
* MT-CO3

ATP synthase|

* MT-ATP6
* MT-ATP8

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

see also mitochondrial diseases

de:Creatin-Kinase it:Creatinchinasi

Template:WH Template:WS

1. ↑ 1.0 1.1 1.2 1.3 Sahni G (2012). "Chest pain syndromes in pregnancy". Cardiol Clin. 30 (3): 343–67. doi:10.1016/j.ccl.2012.04.008. PMID 22813362.
2. ↑ 2.0 2.1 2.2 Shivvers SA, Wians FH, Keffer JH, Ramin SM (1999). "Maternal cardiac troponin I levels during normal labor and delivery". Am J Obstet Gynecol. 180 (1 Pt 1): 122. PMID 9914590.CS1 maint: Multiple names: authors list (link)

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