Creatine kinase isoforms

Abendschein D, Seacord LM, Nohara R, Sobel BE, Jaffe AS. Prompt detection of myocardial injury by assay of creatine. kinase isoforms in initial plasma samples. Clin Cardiol 1988 11 661-4. 

Creatine kinase isoforms s % Total activity Fractional activity... 

Creatine kinase, creatine kinase myocardial band Creatine kinase (CK) enzymes are found in many isoforms, with varying concentrations depending on the type of tissue. Creatine kinase is a general term used to describe the nonspecific total release of all types of CK, including that found in skeletal muscle (MM), brain (BB) and heart (MB). CK MB is released into the blood from necrotic myocytes in response to infarction and is a useful laboratory test for diagnosing myocardial infarction. If the total CK is elevated, then the relative index (RI), or fraction of the total that is composed of CK MB, is calculated as follows RI = (CK MB/CK total) x 100. An RI greater than 2 is typically diagnostic of infarction. 

Winnard, P. Cashon, R.E. Sidell, B.D. Vayda, M.E. Isolation, characterization and nucleotide sequence of the muscle isoforms of creatine kinase from the Antarctic teleost Chaenocephalus aceratus. Comp. Biochem. Physiol. B, 134B, 651-667 (2003)... 

Ye, Y. Wang, C. Zhang, J. Cho, Y.K. Gong, G. Murakami, Y. Bache, R.J. Myocardial creatine kinase kinetics and isoform expression in hearts with severe LV hypertrophy. Am. J. Physiol., 281, H376-H386 (2001)... 

Harder, G. McGowan, R. Isolation and characterization of the muscle-specific isoform of creatine kinase from the zebrafish, Danio rerio. Biochem.-Cell Biol., 79, 779-782 (2001)... 

Although it is true that abnormal proteins increase with age, most of them are a result of posttranslational changes. An example is the various isoforms of creatine kinase (CK). Here, the major isoenzyme, CK-MM (isoform CK-33), is normally synthesized in the heart and skeletal muscle. However, after its release into the circulation, carboxypeptidase hydrolyzes the terminal lysine from one of the M-peptides to form CK-32. Subsequent hydrolysis of the terminal lysine from the second M-peptide produces the third isoform, CK-3i (W8). Numerous similar posttranslational proteins are produced. Hence, the presence of abnormal proteins per se does not support this aging theory. 

Panteghini M. Serum isoforms of creatine kinase isoenzymes. Clin Biochem 1988 21 211-8. 

Abendschein DR, Fontanet HL, Nohara R. Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing. Clin Chem 1990 36 723-7. 

Christenson RH, Russell ME, Pizzo CM. Creatine kinase-MB isoforms fractionated by immunoprecipi-tation and quantified in a rapid analyzer. Clin Chem 1990 36 1127-33. 

Muscle cells which arc damaged will leak creatine kina.se into the plasma. This enzyme exists in different isoforms. CK-MM or total CK is used as an index of skeletal mu.scle damage. Very high serum levels may be expected in patients who have been convulsing or have muscular damage due to electrical shock or crush injury. Creatine kinase concentrations may also be high in acute spells in muscular dystrophy. For these rea.sons, when CK is used as an indicator of myocardial infarction. it is better to measure the MB... 

Within the same individual, the primary structure of many proteins varies with the stage of development and is present in fetal and adult isoforms, such as fetal and adult hemoglobin. The primary structure of some proteins, such as creatine kinase, can also vary between tissues (tissue-specific isozymes) or between intracellular locations in the same tissue. Electrophoretic separation of tissue-specific isozymes has been useful in medicine as a means of identifying the tissue site of injury. 

Proteins that differ somewhat in primary structure and properties from tissue to tissue, but retain essentially the same function, are called tissue-specific isoforms or isozymes. The enzyme creatine kinase is an example of a protein that exists as tissue-specific isozymes, each composed of two subunits with 60 to 72% sequence homology. Of the two creatine kinases that bind to the muscle sarcomere, the M form is produced in skeletal muscle, and the B polypeptide chains are produced in the brain. The protein comprises two subunits, and skeletal muscle therefore produces an MM creatine kinase, and the brain produces a BB form. The heart produces both types of chains and therefore forms a heterodimer, MB, as well as an MM dimer. Two more creatine kinase isozymes are found in mitochondria, a heart mitochondrial creatine kinase, and the universal isoform found in other tissues. (In general, most proteins present in both the mitochondria and cytosol will be present as different isoforms.) The advantage conferred on different tissues by having their own isoform of creatine kinase is unknown. However, tissue-specific isozymes such as MB creatine kinase are useful in diagnosing sites of tissue injury and cell death. 

Cora Nari is experiencing a second myocardial infarction. Ischemia (a low blood flow) has caused hypoxia (low levels of oxygen) in her heart muscle, resulting in inadequate generation of ATP for the maintenance of low intracellular Na and Ca + levels (see Chapter 19). As a consequence, cells have become swollen and the cytosolic proteins creatine kinase (MB isoform) and troponin (heart isoform) have leaked into the blood. (See Ann Jeina, Chapters 6 and 7). 

Studies on cardiac function in fhe dog and monkey have shown neither troponin-T nor the cardiac selective isoforms of creatine kinase that appeared to be reliable indicators of cardiac pathology of systolic dysfunction. 

Uda K, Ellington WR, Suzuki T. Adverse array of creatine kinase and arginine kinase isoform genes is present in the starlet sea anemone Nematostella vectensis, a cnidarians model system for studying developmental evolution. Gene. 2012 497 214-27. 

Apple, F. S., Y. HeUsten, and P. M. Clarkson (1988). Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise. Clin Chem 34(6) 1102-1104. 

The morphology of the M band in cardiac muscle can be correlated roughly with heartbeat frequency. In general, cardiac M bands give a five line pattern, in which the Ml-line is relatively much stronger than the other M-lines (Pask et al. 1994). Five proteins have been described to be locahsed specifically in the M-band the muscle isoform of creatine kinase, M-protein, myomesin, skelemin and titin. 

Isoforms of Enoyl-ACP Reductase. Protein extracts from seeds and leaf were subjected to two-dimensional electrophoresis and Western analysis. The same four isoforms of ER were present in the leaf and seed material(Fig. 2), indicating that all four genes in 8. napus show increased expression in seeds, rather than switching on a seed specific gene. The denatured isoelectric point of the four isoforms was determined by a comparison with carbamylated creatine kinase(BDH) markers. The relative pi s of the polypeptides are ER I, 5.9 ER II, 6.1 ER III, 6.4 and ER IV, 6.8. 

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