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Creatine Kinase

Creatine Kinase (CK), sometimes referred to as Creatine Phosphokinase (CPK), is an enzyme (EC 2.7.3.2). CK is classified as a transferase, which means it facilitates the transfer of a group from one molecule to another. (Reference 2)

                                           AX + B ---> A + BX

The first three numbers of its EC number indicate that it is a phosphotransferase with a nitrogenous group as the acceptor. CK is a very important enzyme for all organisms, as it catalyzes the conversion of creatine into phosphocreatine. Phosphocreatine is used as an energy source for high energy need cells such as smooth muscle cells. CK is clinically relevant in blood serum assays in that an elevated CK level might indicate muscle wasting or myocardial infarction.

Structure

There are four major isozymes in the CK family and have been characterized on the basis of differences in gene and amino acid sequence, as well as tissue localization and immunogenicity. The four isozymes are the muscle (MM-CK), brain (BB-CK), mitochondrial ubiquitous (Miu-CK) and mitochondrial sarcomeric (Mis-CK). The amino acid sequences of the CK isozymes show six regions of homology which are flanked by seven more variable regions. Many studies have linked these conserved regions with similar functions.

The functional entity of the two mitochondrial CK isozymes is an octamer consisting of four dimers each. (Reference 1)

Creatine Kinase has a very narrow substrate specificity where the only naturally occuring are creatine, glycocyamine, and N-ethylglycocyamine. Other substrates were later found to exist in vitro In the 3D model to the left you can see the creatine and ADP analog sites highlighted in pink.

Mechanism

Creatine Kinase catalyzes the reversible transfer of a phosporyl group from MgATP to creatine. This yields phosphocreatine (PCr) and MgADP as seen below. (Reference 6)

Real World Application

As mention previously, CK is routinely assayed in blood serum samples in a clinical setting. High levels of CK along with other factors such as lactate dehydrogenase and aspartate transaminase have become reliable indicators of myocardial infarctions. These levels are sometimes drawn in patients that have not experienced clear heart attack symptoms but are at risk for such occurences. Normal values are between 60 and 410 IU/L, but these values do not represent the specific isozyme present. Testing of CK levels are also performed in the case of renal discomfort or muscle wasting diseases. Elevated levels might indicate malnourishment, injury,myocarditis,hypothyroidism, or use of statin medications. Lower than average CK levels rheumatoid arthritis or certain hepatic diseases. (Reference 3,4)

References

1. McLeish, M. and Kenyon, G. Relating Structure to Mechanism in Creatine Kinase Critical Reviews in Biochemistry and Molecular Biology, 40:1-20, 2005. DOI: 10.1080.10409230590918577

2. Knopp, J. Knopp's Knotes p47, Fifth Edition.

3. Nienhuis, Mark et. al. Prognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction American Heart Journal, Vol 155, Issue 4, April 2008. pp 673-679

4. Protein Data Bank. http://www.rcsb.org

5. Parker, Beth. Effects of Statins on Creatine Kinase Levels Before and After a Marathon Run. The American Journal of Cardiology Volume 109, Issue 2, pp 282-287

6. Figure. http://en.wikipedia.org/wiki/Creatine_kinase