Plasma aminotransferases

Use of the plasma enzyme alanine aminotransferase (ALT) in monitoring the progress of infectious hepatitis. 

The aminotransferases, aspartate transaminase and alanine transaminase, are enzymes that have increased concentrations in plasma following hepatocellular injury. The highest concentrations are seen in acute viral infections, or ischemic or toxic liver injury. 

Hepatic Effects. Liver function tests (serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase) completed in 11 hexachloroethane workers were within the normal range (Selden et al. 1994). Plasma hexachloroethane levels in these workers, who wore protective equipment, were 7.3 + 6.04 pg/L at the time of the tests (Selden et al. 1993). Mild skin and mucous membrane irritation were reported in the exposed group, suggesting that exposure may have been through either the inhalation or dermal routes of exposure. 

Cottrell et al. (1996) reported that a single oral dose of coumarin produced liver necrosis in mice 200 mg/kg bw coumarin was hepatotoxic to both C3H/He and DBA/2 mice. Hepatotoxicity was characterized by an increase in plasma aminotransferase activity, mild subcapsular linear hepatocyte necrosis and, in some C3H/He mice, centrilobular necrosis. Mice were pretreated with (3-naphthoflavone (80 mg/kg bw), Aroclor 1254 (54, 125 or 162 mg/kg bw) or vehicle alone by intraperitoneal injection for three consecutive days. Twenty-four hours later, a single dose of coumarin (200 mg/kg bw) or vehicle was administered by gavage. Pretreatment with... 

Dayal et al. (1989) treated BALB/c mice intraperitoneally with a single dose of 9 mmol/kg bw 2-nitropropane. In male mice, plasma activities of the hepatic enzymes sorbitol dehydrogenase, alanine aminotransferase and aspartate aminotransferase were significantly elevated, while doses of 6.7 mmol/kg bw were ineffective. In female mice, a dose of 6.7 mmol/kg bw was sufficient to cause hepatotoxicity. Histopathological evaluation revealed hepatic damage, particularly in the periportal region. 

Some enzymes show relatively high activity in only one or a few tissues. The presence of increased levels of these enzymes in plasma thus reflects damage to the corresponding tissue. For example, the enzyme alanine aminotransferase ALT, see p. 248) is abundant in the liver. The appearance of elevated levels of ALTin plasma signals possible damage to hepatic tissue. Increases in plasma levels of enzymes with a wide tissue distribution provide a less specific indication of the site of cellular injury. This lack of tissue specificity limits the diagnostic value of many plasma enzymes. 

Diagnostic value of plasma aminotransferases Aminotrans ferases are normally intracellular enzymes, with the low levels found in the plasma representing the release of cellular contents during normal cell turnover. The presence of elevated plasma levels of aminotransferases indicates damage to cells rich in these enzymes. For example, physical trauma or a disease pro cess can cause cell lysis, resulting in release of intracellular enzymes into the blood. Two aminotransferases—ASTand ALT—are of particular diagnostic value when they are found in the plasma. 

Pattern of serum alanine aminotransferase (ALT) and bilirubin in the plasma, following poisoning with the toxic mushroom Amanita phalloides. 

Reasons for the presence of enzymes in the plasma Enzymes can normally be found in the plasma either because they were specifically secreted to fulfill a function in the blood, or because they were released by dead or damaged cells. Many diseases that cause tissue damage result in an increased release of intracellular enzymes into the plasma. The activities of many of these enzymes (for example, creatine kinase, lactate dehydrogenase, and alanine aminotransferase) are routinely determined for diagnostic purposes in diseases of the heart, liver, skeletal muscle, and other tissues. 

Amino groups are tunneled to glutamate from all amino acids except lysine and threonine. The enzymes are aminotransferases, and they are reversible. The two most important of these enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aminotransferases require pyridoxal phosphate as a coenzyme. The presence of elevated levels of aminotransferases in the plasma can be used to diagnose liver disease. 

Mocarelli et al. (1986) conducted a 6-year study on clinical laboratory parameters of children exposed to 2,3,7,8-TCDD following the Seveso accident. ALT, aspartate aminotransferase (AST), GGT, alkaline phosphatase, cholesterol, and triglycerides in plasma and delta amino levulinic acid in urine were monitored yearly in exposed and control groups beginning in June, 1977, approximately 1 year after the incident. The children were 6-10 years old at the time of the accident 69, 528, and 874 resided in the A, B, and R zones, respectively. Chloracne was seen in 19, 0.7, and 4.6%, of the children in areas A, B, and R, respectively. Blood samples were drawn from 69, 83, and 221 children in areas A, B, and R,... 

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. 

Liver. In humans, chronic Cd exposure does not typically result in hepatotoxicity. In laboratory animals, the liver accumulates the largest concentrations of Cd after acute or chronic exposures. In chronically exposed rats, liver injury occurs prior to renal dysfunction. Chronic Cd effects in the liver include increased plasma activities of alanine and aspartate aminotransferases, structural irregularities in hepatocytes, and decreased microsomal mixed function oxidase and CYP450 activities. Acute exposures in rats result in hepatic necrosis, particularly in parenchymal cells. Additionally, rough endoplasmic reticulum deteriorates, while smooth endoplasmic reticulum proliferates. Mitochondria are also degraded. As is the case with chronic exposure, microsomal mixed function oxidases and CYP450s are inhibited. 

As shown in Table 9.5, there are a number of indices of vitamin Be status available plasma concentrations of the vitamin, urinary excretion of 4-pyridoxic acid, activation of erythrocyte aminotransferases by pyridoxal phosphate added in vitro, and the ability to metabolize test doses of tryptophan and methionine. None is wholly satisfactory and where more than one index has been used in population studies, there is poor agreement between the different methods (Bender, 1989b Bates et al., 1999a). 

Several tests are available for asses ing vitamin B status measurement of plasma levels of PLP, measurement of the percentage stimulation of red blood cell glula-matc-oxaloacetate aminotransferase, measurement of the daily excretion of urinary pyridoxic acid, and the tryptophan load test. 

BCAA catabolism, 209 chemical structure, 18 plasma concentrahon, 465 waste nitrogen and, 209-210 Alanine aminotransferase, 426 Alanine cycle, amino transferases and, 427-428... 

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