Lactate dehydrogenase, isoenzyme

Gay, R. J. McComb, R. B. and Bowers, G. N. Optimum reaction conditions for human lactate dehydrogenase isoenzymes as they affect total lactate dehyrogenase activity. Clin. Chem. (1968), U, 740-753. 

Rosalki, S. B. Standardization of isoenzyme assays with special reference to lactate dehydrogenase isoenzyme electrophoresis. Clin. Biochem. (1974), 2> 29-40. 

Bittar, P. G., Charnay, Y., Pellerin, L. etal. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. /. Cereb. Blood Flow Metab. 16 1079-1089,1996. 

The isoenzymes within a particular family will operate under slightly different circumstances or may respond differently to metabolite feedback regulation. In this case there is some degree of structural similarity between the different isoenzymes. The usual example used to illustrate this point is lactate dehydrogenase (LD), which has five isoenzymes, each composed of four sub-units. The subunits are of two types, H or M, so the five forms arise as follows ... 

Why is it desirable to have an enzyme in heart which works efficiently to remove lactate, that is an isoenzyme of lactate dehydrogenase with a low Km for lactate ... 

Lactate dehydrogenase exists in the cytoplasm of humans and most animals as five forms which are easily separable by electrophoresis and are evenly spaced on electropherograms.8 This enzyme is a tetra-mer made of two kinds of subunits. Isoenzyme 1, which has the highest electrophoretic mobility, consists of four identical type B subunits. The slowest moving tetramer (isoenzyme 5) consists of four type A subunits, while the other three forms, AB3, A2B2, and A3B, contain... 

Most NAD+- or NADP+- dependent dehydrogenases are dimers or trimers of 20- to 40-kDa subunits. Among them are some of the first enzymes for which complete structures were determined by X-ray diffraction methods. The structure of the 329-residue per subunit muscle (M4) isoenzyme of lactate dehydrogenases (see Chapter 11) from the dogfish was determined to 0.25 nm resolution by Rossmann and associates in 1971.2 1 More recently, structures have been determined for mammaliam muscle and heart type (H4) isoenzymes,5 for the testicular (C4) isoenzyme from the... 

Elevated pyruvate concentration inhibits the heart muscle lactate dehydrogenase (LDH) isoenzyme but not the skeletal muscle LDH isoenzyme. 

Tang PT, Wang XP, Lu DS. 1992. Changes in lactate dehydrogenase isoenzymes of mitochondriaand microsomes in hepatic damage caused by phosphorus, sodium arsenite, and carbon tetrachloride. Zhongguo Yaolixue Yu Dulixue Zazhi 6(4) 292-296. 

Isoenzymes Isoenzymes are different forms of an enzyme which catalyze the same reaction, but which exhibit different physical or kinetic properties. The isoenzymes of lactate dehydrogenase (LDH) can be separated electrophoretically and can be used clinically to diagnose a myocardial infarction. 

An example of an enzyme which has different isoenzyme forms is lactate dehydrogenase (LDH) which catalyzes the reversible conversion of pyruvate into lactate in the presence of the coenzyme NADH (see above). LDH is a tetramer of two different types of subunits, called H and M, which have small differences in amino acid sequence. The two subunits can combine randomly with each other, forming five isoenzymes that have the compositions H4, H3M, H2M2, HM3 and M4. The five isoenzymes can be resolved electrophoretically (see Topic B8). M subunits predominate in skeletal muscle and liver, whereas H subunits predominate in the heart. H4 and H3M isoenzymes are found predominantly in the heart and red blood cells H2M2 is found predominantly in the brain and kidney while HM3 and M4 are found predominantly in the liver and skeletal muscle. Thus, the isoenzyme pattern is characteristic of a particular tissue, a factor which is of immense diagnostic importance in medicine. Myocardial infarction, infectious hepatitis and muscle diseases involve cell death of the affected tissue, with release of the cell contents into the blood. As LDH is a soluble, cytosolic protein it is readily released in these conditions. Under normal circumstances there is little LDH in the blood. Therefore the pattern of LDH isoenzymes in the blood is indicative of the tissue that released the isoenzymes and so can be used to diagnose a condition, such as a myocardial infarction, and to monitor the progress of treatment. 

Lactate dehydrogenase (LDH) is an oxidoreductase that catalyzes the conversion of lactate to pyruvate. It consists of four subunits that may be of two different types M and H ( muscle and heart formerly known as A and B, respectively). Five different isoenzymes are therefore possible, depending on the subunit composition ... 

Several markers should no longer be used to evaluate cardiac disease, including aspartate aminotransferase, total CK, total lactate dehydrogenase (LDH), and LDH isoenzymes. Due to their wide tissue distribution, these markers have poor specificity for the detection of cardiac injury. Because total CK and CK-MB have served as standards for so many years, some laboratories may continue to measure them to allow for comparisons to cardiac troponin over time, before discontinuing use of CK and CK-MB. In addition, the use of total CK in developing countries may be the preferred or only alternative for financial reasons. However, it should be clear that, for monitoring ACS patients to assist in clinical classification, cardiac troponin is the preferred biomarker. 

Jaffe AS, Landt Y, Parvin CA,et al. Comparative sensitivity of cardiac troponin I and lactate dehydrogenase isoenzymes for diagnosing acute myocardial infarction. Clin Chem 42 1770-1776,1996. 

Both aspartate aminotransferase and alanine aminotransferase are released into the blood after damage to tissues or after cell death. Consequently, they are used as diagnostic tools when heart or liver damage has occurred, such as after a heart attack or in hepatitis, respectively. Other enzymes are also released into the blood at such times. For example, damage to heart muscle is further characterized by the presence of isoenzymes of creatine kinase or lactate dehydrogenase in the plasma. 

Pejovic, M., Stankovic, a., Mitrovic, D. R. (1992). Lactate dehydrogenase activity and its isoenzymes in serum and synovial fluid of patients with rheumatoid arthritis and osteoarthritis. 

Agarose gel electrophoresis (typically 0.7-1 % agarose w/v) is increasingly used in clinical laboratories in place of cellulose acetate, for example in zone electrophoresis of serum proteins, isoenzyme analysis of lactate dehydrogenase and creatine kinase, and immunoelectrophoresis. 

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