Liver enzymes glutamate dehydrogenase

Elevated activities of liver enzymes (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase) were found in the serum of rats exposed continuously to 26 ppm phenol vapor for 15 days (Dalin and Kristoffersson 1974). Increased concentration of these enzymes in serum is often associated with liver injury but is not conclusive evidence for the type or severity of injury. Therefore, 26 ppm can be considered a less serious LOAEL in rats. Serum levels of... 

Ammonia is normally condensed with 2-oxoglutarate and thus converted to glutamate via the enzyme glutamate dehydrogenase this enzyme is of highest activity in the liver and kidney. Glutamate is produced from 2-oxoglutarate and ammonia as follows ... 

Reactions of the urea cycle occur in both the mitochondria and cytosol of liver cells. Glutamate dehydrogenase, the citric acid cycle enzymes, carbamoyl phosphate synthetase I, and ornithine transcarbamoylase are localized in the mitochondrion, whereas the rest of the cycle occurs in the cytosol. This means that ornithine must be transported into mitochondria, and citrulline must be exported to the cytosol, in order for the cycle to proceed. 

The conversion of glutamic acid to a-keto glutaric acid is catalysed by a highly specific enzyme, glutamic dehydrogenase, found chiefly in liver and kidney. 

The major enzyme involved in the formation of ammonia in the liver, brain, muscle, and kidney is glutamate dehydrogenase, which catalyzes the reaction in which ammonia is condensed with 2-oxoglutarate to form glutamate (Sec. 15.1). Small amounts of ammonia are produced from important amine metabolites such as epinephrine, norepinephrine, and histamine via amine oxidase reactions. It is also produced in the degradation of purines and pyrimidines (Sec. 15.6) and in the small intestine from the hydrolysis of glutamine. The concentration of ammonia is regulated within narrow limits the upper limit of normal in the blood in humans is 70/tmol L-1. It is toxic to most cells at quite low concentrations hence there are specific chemical mechanisms for its removal. The reasons for ammonia toxicity are still not understood. The activity of the urea cycle in the liver maintains the concentration of ammonia in peripheral blood at 20/ molL. ... 

Figure 3. Schematic representation of five enzyme activity levels in blood serum as a result of various liver diseases. These data (28) do not show the large range in values among individuals. GOT, glutamate-oxaloacetate transaminase GPT, glutamate-pyruvate transaminase GlDH, glutamate dehydrogenase LDH, lactate dehydrogenase P, alkaline phosphatase.

Enzymes in this category include alanine and aspartate aminotransferases, glutamate dehydrogenase (GLD), ATP, 5 -nucleotidase (NTP), y-glutamyl transferase (GGT), glutathione S-transferase (GST), and serum cholinesterase (CHE). The aminotransferases and ALP are widely used. They have long been mistakenly called, as a group, liver function tests. They are not, of course, but the habit persists. GGT is widely available in the United States and on automated analyzers. The others have not been adopted as widely. 

Glutamate dehydrogenase (EC 1.4.1.3 L-glutamate NAD(P) oxidoreductase, deaminating GLD) is a mitochondrial enzyme found mainly in the liver, heart muscle, and kidneys, but small amounts occur in other tissue, including brain and skeletal muscle tissue, and in leukocytes. 

Fractionation of beef liver shows an aggregation of zinc as glutamic dehydrogenase activity to protein ratio reaches its maximum value. Simultaneously, the metal protein ratio of all other elements studied decreases with increasing enzyme purity. The zinc/protein and activity/protein ratios become maximal in the third crystallization. 

This reaction is close to equilibrium in the liver, and the direction of the reaction is determined by the concentrations of reactants and products. Normally, the reaction is driven forward by the rapid removal of ammo-aium ion. Glutamate dehydrogenase is located in mitochondria, as are some of the other enzymes required for the production of urea. This compart-mentalization sequesters free ammonium ion, which is toxic. 

Often there is no good clinical test available to determine the exact type of hepatic lesion, short of liver biopsy. There are certain patterns of enzyme elevation that have been identified and can be helpful (Table 38-3). ° The specificity of any serum enzyme depends on the distribution of that enzyme in the body. Alkaline phosphatase is found in the bile duct epithelium, bone, and intestinal and kidney cells. 5-Nucleotidase is more specific for hepatic disease than alkaline phosphatase, because most of the body s store of 5 -nucleotidase is in the liver. Glutamate dehydrogenase is a good indicator of centrolobular necrosis because it is found primarily in centrolobular mitochondria. Most hepatic cells have extremely high concentrations of transaminases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are commonly measured. Because of their high concentrations and easy liberation from the hepato-cyte cytoplasm, AST and ALT are very sensitive indicators of necrotic lesions within the liver. After an acute hepatic lesion is established, it may take weeks for these concentrations to return to normal. ... 

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