Bile duct ligation in rats increased alkaline phosphatase activity in serum and liver. In the serum, the activity reached a peak 24 h after bile duct ligation, earlier than in the liver. This finding indicates that the elevation of serum alkaline phosphatase activity is not due to simple overspill of this enzyme from the liver into the circulation. An electrophoretic study, employing polyacrylamide gel with Triton X-100, and a gel filtration study disclosed that 24 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphatase in addition to the hepatic and intestinal isoenzymes. The high molecular weight form was also found in bile, indicating that regurgitation of bile contributed to the increase in alkaline phosphatase activity in the serum. The absence of the high molecular weight alkaline phosphatase in the sera of rats with intrahepatic cholestasis induced by α-naphthylisothiocyanate suggests that, in this type of cholestasis, regurgitation of bile alkaline phosphatase does not play an important role in the elevation of serum alkaline phosphatase activity. These findings indicate that the high molecular weight alkaline phosphatase in serum is a useful diagnostic marker of biliary obstruction.
"Nevertheless, several features of much of the cholephilic enzyme activity found in the blood are not entirely answered by either of these pathways. These features include the fact that much of the cholephilic enzyme activity found in the blood is relatively low molecular weight and hydrophilic, while almost all of the activity found in bile is hydrophobic (Inoue et al., 1980; Toda et al., 1980; Tsuji et al., 1980; Selvaraj et al., 1984), and the hydrophobic forms found in blood frequently present within large particles that have biochemical characteristics consistent with their originating from basolateral, not apical, membranes (De Broe et al., 1985; Kihn et al., 1991). These particles are not found in bile and are believed to be membrane fragments shed from the basolateral surfaces of liver cells (Deng et al., 1996b; Van Hoof et al., 1997). "
[Show abstract][Hide abstract] ABSTRACT: Testing the blood for evidence of hepatic damage and dysfunction frequently involves measuring several blood constituents simultaneously to screen for disease. While useful, this approach occasionally leads to apparent disparities between the blood test results, and the results of other diagnostic tests such as histology. In part, these perceived discrepancies may stem from a lack of appreciation for tissue, cellular, and molecular factors that affect the appearance of hepatic disease biomarkers in the blood. Further confusing the matter is that in some instances the mechanisms responsible for the appearance of diagnostic compounds in blood are only partially understood. Many of the known factors that affect hepatic biomarkers are similar to those affecting other tissue markers, while others are unique to the liver, such as those involved with cholestasis. Disease conditions can also cause misleading results by affecting tissue concentrations of test compounds, hepatic mass, and the clearance rate of compounds from the blood. Knowledge of the factors affecting the blood concentrations of biomarkers, as well as investigations into the mechanisms behind changes to hepatic biomarker concentrations, may allow for a better interpretation of blood test results and fewer inconsistencies between diagnostic results.
[Show abstract][Hide abstract] ABSTRACT: The alterations of the alkaline phosphatase (ALP) activity in the rat liver following bile duct ligation were investigated by electron microscopical techniques. Serum ALP activity reached the maximum at 24 hours after ligation and two isozymes of ALP, high molecular and low molecular one, appeared in the serum. Bile canaliculi became dilated at 48 hours after ligation and the microvilli were destructed and diminished in number. ALP activity was observed almost only on the bile canalicular membrane of the liver cells in the control. On the other hand, in the bile duct-ligated rat, the ALP activity on the canalicular membrane was markedly increased initially, then it appeared on the lateral membrane, and finally on the sinusoidal membrane also. It was not stainable on the canalicular membranes which lacked microvilli. The proposed pathway through which hepatic ALP enters the blood stream in bile duct-ligated rats is as follows: ALP, being synthesized in the microsomes of hepatocytes, is initially transferred to the bile canalicular membrane and diffused to lateral membrane through tight junction, reaches to sinusoidal membrane then released into the blood stream.
[Show abstract][Hide abstract] ABSTRACT: The review discusses the similarities and differences between the common isoenzymatic forms of ALP. Methods for separating, measuring, and purifying the isoenzymes on the basis of these differing properties are described. The evidence is reviewed for the existence of different genes coding for different isoenzymes, and the current state of knowledge is surveyed concerning the location, development, function, and regulation of the isoenzymes. Finally, some unusual forms of ALP which may appear in the circulation are described.
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