Lactate dehydrogenase distribution

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. 

Few studies aimed at understanding the effects of pressure on metabolism in fish have been performed in the Black Sea or Sea of Azov because no distinct stratification was found in the distribution of water animals there. The Sea of Azov is saucer-like, its maximum depth being only 15 m, and in the Black Sea the oxygenated water layer extends only to 150 m depth. However, Emeretli (1996) has shown that activity of lactate dehydrogenase in the liver increases 2-10 times in scorpion fish and annular bream placed in a barorespirometer (designed by A. Stolbov) and sunk to a depth of 300 m. This response seems to be peculiar to shallow-water species (Hochachka and Somero, 1984). 

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. 

There are five enzymes that are commonly used in diagnosis of liver disease Aspartate aminotransferase (AST EC 2.6.1.1), alanine aminotransferase (ALT EC 2.6.1.2), alkaline phosphatase (ALP 3.1.3.1), and y-glutamyl transferase (GGT EC 2.3.2.2), are commonly used to detect liver injury, and lactate dehydrogenase (LD EC 1.1.1.27) is occasionaEy used. ALT and GGT are present in several tissues, but plasma activities primarily reflect liver injury. AST is found in liver, muscle (cardiac and skeletal), and to a liipited extent iti fed cells. LD has wide tissue distribution, and is thus relatively nonspecific. ALP is found in a number of tissues, but in normal individuals primarEy reflects bone and liver sources. Thus based on tissue distribution, ALT and GGT would seem to be the most specific markers for liver injury. 

H17. Hultin, H. O., and Westort, C., Factors affecting the distribution of lactate dehydrogenase between particulate and non-particulate fractions of homogenized skeletal muscle. Arch. Biochem. Biophys. 117, 523-533 (1966). 

The diagnosis of organ disease is aided by measurement of a number of enzymes characteristic of that tissue or organ. Most tissues have characteristic enzyme patterns (Table 8-2) that may be reflected in the relative serum concentrations of the respective enzymes in disease. The diseased tissue can be further identified by determination of the isoenzyme pattern of one of these enzymes (e.g., lactate dehydrogenase, creatine kinase) in the serum, since many tissues have characteristic isoenzyme distribution patterns for a given enzyme. For example, creatine kinase (CK) is a dimer composed of two subunits, M (for muscle) and B (for brain), that occur in three isoenzyme forms, BB(CKi), MB(CK2) and MM(CK3), which catalyze the reversible phosphorylation of creatine with adenosine triphosphate (ATP) as the phosphate donor ... 

Laughton JD, Charnay Y, Belloir B, Pellerin L, Magistretti PJ, et al. 2000. Differential messenger RNA distribution of lactate dehydrogenase LDH-1 and LDH-5 isoforms in the rat brain. Neuroscience 96 619-625. 

SUBCELLULAR DISTRIBUTION OF CKAc, LACTATE DEHYDROGENASE AND PROTEIN IN RAT HIPPOCAMPAL... 

Several of the common enzyme measurements aimed at detecting hepatotoxicity are not specific to the liver, show a widespread tissue distribution, and are therefore affected by damage to extrahepatic tissue (e.g., alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase following injury to cardiac or skeletal muscles). The development of troponin assays has provided an alternative to enzyme measurements as indicators of cardiotoxicity, but not for myotoxicity here, the timing and the methods of sample collection are particularly critical for the detection of cardiac or muscle damage (see Chapter 7). 

In the course of electrophoretic studies it has been found that some enzymes exist in several distinct forms in a single organism and that the distribution patterns of the various forms may vary not only from tissue to tissue but also in the same tissue at different stages of development. Such multiple enzymes which catalyse the same reaction but which vary in their detailed structure and reactivity are known as isoenzymes. Perhaps the best known example is lactate dehydrogenase which is composed of four subunits of two different types, H and M. Five different forms of lactate dehydrogenase have been identified, having the constitution H4, H3M, H2M2, HM3 and M4 respectively. All five catalyse the reaction... 

Another overexpression strategy was tried with the NAD -dependent malic enzyme of E. coli Thermodynamically, the reduction of pyruvate to malate is favored, but in nature this reaction does not occur. A double mutant of E. coli, NZNlll, which is blocked in both pyruvate formate lyase pjT) and lactate dehydrogenase (Idh), was used as the host. It is unable to grow anaerobically because its pyruvate metabolism is blocked by the fermentation end products acetate, formate, ethanol, and lactic acid. The mutant NZNl 11 with multiple copies of malic enzyme accumulated succinic acid as a major end product only when the cells were switched to anaerobic metabolism gradually by metabolic depletion of oxygen in a sealed tube (Clark et al. 1988). Mutant strains blocked in either pfl or Idh did not alter their distribution of fermentation products when overexpressing malic enzyme. 

---