Creatine Kinase, MM Form (CKMM/CPK-MM/CK-3)

EC 2.7.3.2

Creatine kinase is also sometimes referred to as creatine phosphokinase, creatine phosphotransferase, CPK or just CK. All isoenzymes of CK catalyze the phosphorylation of creatine to form phosphocreatine. Very high levels of CK are found in skeletal muscle, primarily the MM form. Phosphocreatine is used as an energy storage system in muscle tissue with CK serving to catalyze the reverse reaction: The rapid formation of ATP from phosphocreatine and ADP when ATP is needed by the tissue¹.

CK is a dimeric enzyme. There are two common gene products, one coding for the subunit (so named because of its predominance in muscle) and the other for the B subunit (so named because of its predominance in brain tissue). The three common forms of active CK include two homodimers and one heterodimer. The first homodimer (CK-1) consists of two B subunits and is referred to as CKBB. The other has two M subunits and is referred to as CKMM (CK-3). The heterodimer has one of each subunit and is referred to as CKMB (CK-2)². There is a third gene product which results in the mitochondrial form of CK.

CKMM is a very important constituent of active muscle, and it has been shown to increase with prolonged exercise³. Also, when measuring total CK or just serum CK in normal serum, it is really CKMM that is being measured since it accounts for the vast majority of CK activity normally found in serum from healthy adults^4,5. Significant levels of CKMM activity are also found in cardiac muscle and therefore a large increase in total CK was once used as a tool in the diagnosis of acute myocardial infarction (AMI)⁶. Once the CK isoenzymes were elucidated and isoenzyme tests became available, CKMB quickly became the marker of choice for AMI, only to be surpassed later by the cardiac troponins. However where CKMM (usually just measured as total CK) still has an important role to play is in pathologies of skeletal muscle including the diagnosis, monitoring and assessment of carrier status of muscular dystrophy^7,8,9. CKMM also plays a useful role in diagnosis, prognosis and treatment monitoring of muscle diseases such as polymyositis, dermatomyositis and in ruling out others such as polymyalgia rheumatica^10-13.

There are no useful spectrophotometric changes that occur during the CK reaction, but a very common way of measuring CK activity is to couple the production of ATP in the reverse reaction with glucose and hexokinase which results in glucose-6-phosphate, which is then coupled with its dehydrogenase reaction (catalyzed by G6PDH) which uses NADP, the reduction of which can be monitored by an increase of absorbance at 340 nm. The CK isoenzymes have different isoelectric points and thus can be readily distinguished and quantified by electrophoresis using chromogenic substrate stains.