Creatine Kinase (CK) Isoenzymes and Clinical Significance

Vocabulary flashcards covering creatine kinase structure, tissue sources, isoenzymes, atypical forms, diagnostic significance, determination methods, analytical errors, and reference values.

Creatine Kinase (CK)

An enzyme ($\text{E.C. 2.7.3.2}$, $\text{MW } 82{,}000\,\text{Da}$) that catalyzes the reversible phosphorylation of creatine by ATP, playing a vital role in high-energy phosphocreatine production for muscle contraction and transport systems.

Creatine Phosphokinase (CPK)

The common alternative name and abbreviation for the enzyme creatine kinase.

B Subunit (CK)

The brain subunit of creatine kinase with a molecular weight of approximately $40{,}000\,\text{Da}$, which forms dimeric isoenzymes when paired with another subunit.

M Subunit (CK)

The muscle subunit of creatine kinase with a molecular weight of approximately $40{,}000\,\text{Da}$, which forms dimeric isoenzymes when paired with another subunit.

CK-BB (CK1)

The brain-type isoenzyme of creatine kinase composed of two B subunits ($\text{BB}$), which migrates fastest toward the anode during electrophoresis.

CK-MB (CK2)

The hybrid-type isoenzyme of creatine kinase composed of one M subunit and one B subunit ($\text{MB}$), representing $25\text{--}46\%$ of CK activity in heart muscle.

CK-MM (CK3)

The muscle-type isoenzyme of creatine kinase composed of two M subunits ($\text{MM}$), which constitutes $94\text{--}100\%$ of normal serum CK and exhibits the slowest electrophoretic mobility.

Electrophoretic Migration Pattern of CK Isoenzymes

The migration pattern of CK isoenzymes from cathode to anode, where CK-BB (CK1) migrates fastest, followed by CK-MB (CK2), and CK-MM (CK3) which moves slowest.

Macro-CK

An atypical complex form of CK that migrates on electrophoresis between CK-MM and CK-MB, observed in $0.8\text{--}1.6\%$ of serum samples, particularly in women older than $50\,\text{years}$.

Macro-CK Type 1

An atypical form of CK consisting of CK-1 (CK-BB) complexed with IgG, or CK3 complexed with IgA.

Macro-CK Type 2

An atypical oligomeric form of mitochondrial CK (CK-Mt).

Mitochondrial CK (CK-Mi)

The 4th CK isoenzyme ($\text{MW } 350{,}000\,\text{Da}$) bound to the outer surface of inner mitochondrial membranes, constituting up to $15\%$ of cardiac CK activity and migrating cathodic to CK-MM.

Duchenne-type Muscular Dystrophy

A sex-linked progressive muscular dystrophy that causes severe skeletal muscle breakdown and extreme serum CK elevations up to $50 \times$ the upper limit of normal (ULN).

AMI CK-MB Time Course

The unique diagnostic kinetics of CK-MB following acute myocardial infarction, beginning to rise within $4\text{--}8\,\text{hours}$, peaking at $12\text{--}24\,\text{hours}$, and returning to normal within $48\text{--}72\,\text{hours}$.

Reye's Syndrome

A childhood condition resulting in liver and brain swelling following viral infections, which causes elevated levels of serum CK-BB.

Tanzer-Gilbarg Assay

A forward-reaction assay for CK determination with an optimum pH of $9.0$, where absorbance of the produced NADH is measured at $340\,\text{nm}$.

Oliver-Rosalki Method

The most commonly used reverse-reaction assay for CK determination, operating at an optimum pH of $6.8$, which is $2\text{--}6$ times faster than forward assays and measures the rate of NADPH formation.

Adenylate Kinase (AK) Effect

An analytical error caused by AK released from hemolyzed erythrocytes, which reacts with ADP to produce ATP and migrates cathodal to CK-MM, causing falsely elevated CK or CK-MB values.

Reference Range for Total CK (Male)

The normal serum total CK activity in males, defined as $15\text{--}160\,\text{U/L}$ at $37\,^\circ\text{C}$.

Reference Range for Total CK (Female)

The normal serum total CK activity in females, defined as $15\text{--}130\,\text{U/L}$ at $37\,^\circ\text{C}$.

Reference Value for CK-MB

The normal physiological proportion of CK-MB relative to total CK activity, defined as $<6\%$ of total CK.

Electrophoresis (CK Separation)

The reference separation method for CK isoenzymes, in which bands are visualized using bluish-white fluorescence of NADPH under ultraviolet light after incubation with a reverse reaction assay.

Ion-Exchange Chromatography (CK Separation)

A separation technique utilizing charged resins that offers high precision but may suffer from column errors where CK-MM, CK-BB, or Macro-CK merge or elute alongside CK-MB.

Immunoassay Method (CK Determination)

An analytical method using specific antibodies to measure CK-2 enzyme protein concentration rather than catalytic activity, capable of detecting enzymatically inactive CK-2 for earlier infarction diagnosis.

Immunoinhibition Method (CK Determination)

A procedure using anti-CK-M subunit antiserum to inhibit M subunits of CK-MM and CK-MB, allowing remaining B subunit activity to be measured and multiplied by $2$ to calculate total CK-MB activity.

Pronounced CK Elevation

Serum CK activity elevated $5$ or more times above normal, seen in conditions such as Duchenne's muscular dystrophy, polymyositis, dermatomyositis, and acute myocardial infarction.

Mild to Moderate CK Elevation

Serum CK activity elevated $2\text{--}4$ times above normal, seen in severe exercise, surgical procedures, delirium tremens, alcoholic myopathy, pulmonary infarction, and hypothyroidism.