Creatine Kinase (CK) is a dimeric enzyme composed of either M- or B-type subunits. The subunits, each encoded by a unique gene, associate to form three isoenzymic forms: BB, MB, and MM. These isoenzymes are expressed at different levels in various tissues in humans. CK-BB is predominantly found in brain tissue, CK-MB in heart muscle, and CK-MM in skeletal and heart muscle.
CK-BB is not normally present in measurable amounts in the serum of normal adults, although serum levels may increase after severe damage to tissues containing CK-BB. Elevated serum levels of CK-BB are associated with cancer of the breast, ovary, prostate, colon and other gastrointestinal carcinomas, as well as small-cell anaplastic carcinoma of the lung. In addition, CK-BB serum levels may be measured in conjunction with the other isoenzymes, CK-MB and CK-MM, to aid in the diagnosis of myocardial infarction.
CK-MB is known to exist in two forms: CK-MB2, the gene product, and CK-MB1, which is modified upon release into the bloodstream. Carboxypeptidase cleavage of the C-terminal Lysine residue of the M subunit transforms CK-MB2 into CK-MB1. In healthy individuals, CK-MB2 is in equilibrium with the modified CK-MB1 subform at a ratio of approximately 1:1. In the early hours of myocardial infarction, the abrupt release of CK-MB2 from myocardium produces an upward shift in the serum CK-MB2/CK-MB1 ratio, usually before total CK-MB (CK-MB2 + CK-MB1) exceeds normal levels.
Enzymatic assessments of the CK-MB2/CK-MB1 ratio have given way to antibody-based determinations of CK-MB mass. CK-MB mass is often measured as part of a cardiac panel of markers for the detection of myocardial infarction, along with Myoglobin, Troponin I, and Troponin T. CK-MB is also useful in the follow-up of an individual who has suffered a heart attack, helping to detect whether a subsequent infarction has occurred.
Although CK-MM is predominantly found in skeletal muscle, it is also the primary CK isoenzyme present in heart muscle. In fact, serum levels of CK-MM elevate as early as six hours after the onset of myocardial infarction. Serum assays for CK-MM are sensitive for the detection of an infarction, but lack cardiac tissue specificity and, therefore, are used in conjunction with serum assays for CK-MB and CK-BB to rule-in or rule-out the presence of an infarction.
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