What is creatine kinase (CK)?

Creatine kinase (CK) is an enzyme that mainly exists in your heart and skeletal muscle, with small amounts in your brain. The cells in your skeletal muscles, heart muscles or brain release creatine kinase into your blood when they’re damaged.

An enzyme is a protein that acts as a catalyst to bring about a specific biochemical reaction.

The small amount of CK that’s normally in your blood mainly comes from your skeletal muscles (the muscles that are attached to your bones and tendons). Any condition, injury or event that causes muscle damage and/or interferes with muscle energy production or use increases levels of CK in your blood. For example, intense exercise can increase CK levels. Muscle diseases (myopathies) such as muscular dystrophy can also increase CK levels.

There are three types of CK enzymes:

CK-MM: Found mostly in your skeletal muscles.

CK-MB: Found mostly in your heart muscle.

CK-BB: Found mostly in your brain tissue.

What is the function of creatine kinase (CK)?

The regular function of creatine kinase (CK) is not really related to what elevated levels of it may indicate in a blood test. CK’s job is to add a phosphate group, a group of natural chemicals, to creatine, a substance in your muscle cells that helps your muscles produce energy. When CK adds phosphates to creatine, it turns the creatine into the high-energy molecule, phosphocreatine, which your body uses to generate energy.

CK gets into your bloodstream when your muscles, heart or brain experience acute damage or chronic degeneration. When your muscles are damaged, the muscle cells break open, and their contents, including creatine kinase, leak into your bloodstream.

Creatine kinase MM

Creatinine kinase in muscles. Creatinine kinase catalyzes reverse reaction of phosphoryl residue transport from ATP to creatine from creatinine phosphate to ADP. Creatinine phosphokinase acts in a dual manner in the muscular tissue: in sarcoplasm, enzyme transports phosphoryl group from ATP to creatine; resulting creatinine phosphate is used for phosphorylating ADP, which is combined with myosin in myofibrils. This system, along with sodium and potassium and stimulated ATPase, participates in energy supply to the active ion transportation through cell membranes.

Creatine kinase (CK), also known as creatine phosphokinase (CPK or CFK) or phosphocreatine kinase, is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses 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 and heart, but also brain, photoreceptor cells of the retina, hair cells of the inner ear and so on, 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. Thus, creatine kinase is an important enzyme in such tissues.

Heart contains mainly MM and MB forms.

What does a high level of creatine kinase (CK) mean?

Having a high level of creatine kinase (CK), or a rise in levels in subsequent CK tests, generally indicates that you have experienced some recent muscle damage. A CK test can’t indicate which muscle(s) was damaged or the cause of the damage.

Other causes of increased creatine kinase (CK) levels

Certain conditions and injuries that aren’t directly related to your muscles can cause elevated CK levels, including:

Hormonal (endocrine) disorders, such as thyroid disease, Addison’s disease or Cushing’s syndrome.

Prolonged surgeries.

Seizures.

Infections (viral, bacterial, fungal or parasitic).

Connective tissue disorders, such as lupus and rheumatoid arthritis.

Celiac disease.

Kidney (renal) failure.

High fever accompanied by shivering.

A blood clot.

Any drug or toxin that interferes with muscle energy production or increases energy requirements.

Shot injections.

Abnormalities. Disorders or diseases caused or related.

A considerable increase of creatine kinase (CK/CFK) is seen with musculoskeletal disorder and in acute myocardial infarction. Thus, CK/CFK activity increases earlier than the activity of other enzymes [3].

Creatine kinase will increase with muscle, heart, or brain damage – these can be caused by an underlying disease or disorder, including [3,5]:

Muscle injuries, physical trauma, and burns;

Genetic muscle disorder, such as muscular dystrophy (i.e Duchenne muscular dystrophy);

Infections by viruses, bacteria, fungi, or parasites, causing muscle wasting;

Fever, accompanied by shivering;

Hypothermia, a dangerous drop in body temperature;

Hormonal disorders, such as hypothyroidism, Addison’s disease, acromegaly (a disorder where the pituitary gland produces too much growth hormones), and Conn’s syndrome/hyperaldosteronism (a condition where too much aldosterone is produced in the adrenal glands);

Metabolic disturbances such as hyponatremia (low sodium), hypokalemia (low potassium), or hypophosphatemia (low phosphate)

Diabetes; when it causes muscle dysfunction (myopathy);

Some cases of autoimmune diseases when there is muscle involvement, such as lupus, rheumatoid arthritis, and celiac disease;

Heart attacks;

Head/brain injury;

Seizures;

Some cancers;

Medical interventions, like injections and surgery;

and in various central nervous system diseases:

schizophrenia,

manic-depressive psychosis,

syndromes, induced by psychotropic agents.

also

in athletes in training process and at rest,

in obese and overweight people,

in people taking drugs (like cocaine) and medications (like statins, fibrates, beta-blockers, glucocorticoids, antipsychotic, antibiotic, etc.).

The most common cause of low creatine kinase levels is [4,5]

Low muscle mass - muscle wasting (muscle atrophy) due to physical inactivity, illnesses, or old age;

Inflammation in Autoimmune Disease - creatine kinase levels can be significantly reduced in autoimmune diseases, such as lupus and rheumatoid arthritis. The more inflammation there is, the lower creatine kinase levels can get;

Pregnancy - total creatine kinase levels are reduced in the second trimester of pregnancy. However, they increase in late pregnancy.

1.    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 ( Pt 1) (1): 21–40. doi:10.1042/bj2810021. PMC 1130636. PMID 1731757.

2.     Wallimann T, Hemmer W (1994). "Creatine kinase in non-muscle tissues and cells". Molecular and Cellular Biochemistry. 133–134 (1): 193–220. doi:10.1007/BF01267955. eISSN 1573-4919. PMID 7808454.

3.     Moghadam-Kia S, Oddis CV, Aggarwal R (January 2016). "Approach to asymptomatic creatine kinase elevation". Cleveland Clinic Journal of Medicine. 83 (1): 37–42. doi:10.3949/ccjm.83a.14120. PMC 4871266. PMID 26760521

4.    Sidney B Rosalki, Low Serum Creatine Kinase Activity, Clinical Chemistry, Volume 44, Issue 5, 1 May 1998, Page 905, https://doi.org/10.1093/clinchem/44.5.905

5.    Biljana Novkovic. Creatine Kinase Test: High & Low Levels + Normal Range. | Last updated: March 2, 2021. Medically reviewed by Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD. Available online https://labs.selfdecode.com/blog/creatine-kinase/