What is creatine phosphokinase (CPK)?

What is CPK (Creatine Phosphokinase)?

CPK (creatine phosphokinase), also called creatine kinase (CK), is an enzyme that catalyzes the reversible transfer of phosphate between creatine and ATP, playing a crucial role in cellular energy metabolism in tissues with high energy demands like muscle and heart. 1, 2

Biochemical Function

CPK catalyzes the reversible reaction: phosphocreatine + MgADP⁻ + H⁺ ↔ MgATP²⁻ + creatine 2, 3

• This reaction either re-phosphorylates ADP to ATP or stores immediately available energy as phosphocreatine, functioning as a reservoir of "high-energy phosphate" that supplies ATP on demand 2, 3
• The enzyme has a molecular size of approximately 82 kDa, which prevents it from entering the bloodstream under normal conditions 1, 2
• CPK plays a significant role in energy homeostasis of cells with intermittently high energy requirements 3

CPK Isoenzymes

There are three main CPK isoenzymes with distinct tissue distributions: 4

• CK-MM: Predominantly found in skeletal muscle 4
• CK-MB: Primarily located in myocardium (heart muscle) 4, 5
• CK-BB: Present in brain and smooth muscle 4
• Mitochondrial CK (CKm): A fourth isoenzyme involved in mitochondrial oxidative phosphorylation 4, 6

Primary Clinical Applications

Cardiac Injury Detection

• CK-MB remains useful for diagnosing early reinfarction and periprocedural myocardial injury despite being superseded by troponins for initial MI diagnosis, because its shorter half-life makes it superior for detecting reinfarction 1, 2
• CK-MB by mass immunoassay should be obtained at baseline and compared with samples 6-12 hours later when symptoms recur 1
• Elevated CK-MB is highly specific for myocardial injury, as myocardium is the only tissue containing sufficient MB isoenzyme to cause substantial serum elevations 1, 5
• Approximately 30% of patients with chest pain and normal CK-MB actually have NSTEMI when assessed with troponin, highlighting CK-MB's lower sensitivity 1

Skeletal Muscle Injury

• Elevated total CPK without elevated CK-MB indicates skeletal muscle injury rather than cardiac damage 1, 2
• CPK commonly increases after unaccustomed exercise, particularly eccentric contractions 1, 2
• Raising CPK levels above five times normal (approximately 1000 IU/L) is a sign of rhabdomyolysis 7
• CPK levels above 75,000 IU/L are associated with high incidence of acute kidney injury (>80%) in crush syndrome patients 7

Neuromuscular Disease Screening

• CPK measurement is recommended for screening conditions like Duchenne muscular dystrophy in pediatric patients with motor delays and low muscle tone, where levels typically show marked elevation 1, 2
• Muscle enzymes including CPK should be measured at diagnosis and follow-up in patients with juvenile dermatomyositis 1

Other Clinical Scenarios

• CPK elevation, along with leukocytosis, acidosis, and elevated alkaline phosphatase, suggests acute mesenteric ischemia 1
• Routine CPK monitoring is not required during JAK inhibitor treatment, but should be performed if myalgia develops 1

Critical Interpretation Pitfalls

Account for timing of measurement, as CPK levels fluctuate with physical activity and have specific kinetics after exercise 1, 8

• Consider the patient's muscle mass when interpreting results, as baseline CPK correlates with total muscle mass 1
• Be aware that medications may affect muscle function and CPK levels 1
• Physical activity significantly affects CPK and CK-MB variability, emphasizing the need for caution when evaluating acute myocardial infarctions and skeletal muscle injury 8