Alkaline phosphatase liver/bone/kidney

Alkaline phosphatase catalyzes the biochemical splitting of phosphoric acid ester. AP (W.M. Roberts, 1933) is found in the liver, bone, kidney, intestine, lung and placenta. A Regan isoenzyme can be detected as an ectopic variation of placental AP in tumour patients (10-30% of cases). The AP of the liver is located in the cytoplasm and in the membranes, primarily at the biliary pole. Placental AP is also present in the liver. The AP of bile duct epithelia is not elevated in healthy individuals. The serum activity of AP is predominantly due to the isoenzymes of the liver and osteoblasts only 14% are of renal origin. Half-life is 3-7 days. 

As reported earlier (F16, G8), placenta and intestine are two sources of alkaline phosphatase that are equally sensitive to L-phenylalanine. As can be expected, gastric and duodenal contents contain LPSAP as well. Preparations made so far from the following tissues contain much smaller amounts of LPSAP liver, bone, kidney, lung, and spleen, usually of the order of 0-15% (Table 4). 

ALPL NM 000478 TNAP Tissue-nonspecific alkaline phosphatase, TNSALP liver-bone-kidney-type AP Developing nervous system, skeletal tissues, liver, kidney Bone and dental mineralization... 

Studer M, Terao M, Gianni M et al (1991) Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene cell and tissue specific expression. Biochem Biophys Res Commim 179 1352-1360... 

AP had not been used extensively in immunohistochemistry until publication of the unlabeled alkaline phosphatase-antialkaline phosphatase (APAAP) procedure (2, 3). The soluble immune complexes utilized in this procedure have molecular weights of approximately 560 kDa. The major advantage of the APAAP procedure compared to the earlier peroxidase techniques was the lack of interference posed by endogenous peroxidase activity. Because of the potential distraction of endogenous peroxidase activity, the alkaline phosphatase techniques were particularly recommended for use on blood and bone marrow smears. Endogenous alkaline phosphatase activity from bone, kidney, liver and some white cells can be inhibited by the addition of 1 mM levamisole to the substrate solution (4), although 5 mM has been found to be more effective (5). Intestinal alkaline phosphatases are not adequately inhibited by levamisole. 

Unquenched endogenous alkaline phosphatase activity may be seen in leucocytes, kidney, liver, bone, ovary bladder, salivary glands, placenta and gastro-intestinal tissue. Add levamisole to the alkaline phosphatase chromogen reagent or use another enzyme label such as horseradish peroxidase. Intestinal alkaline phosphatase is not quenched by the addition of levamisole. Pretreat the tissue with 0.03 N HCI. 115-121... 

Indicates endogenous alkaline phosphatase activity in the tissue sections. It is present in liver, kidney, Gl tract, bone, bladder, ovary, salivary gland, placenta, leukemic, necrotic or degenerated cells. 

However, other isoenzymes of alkaline phosphatase are found in parts of the body such as bone, kidney, intestine and placenta, hence an isolated raised alkaline phosphatase may not be associated with liver dysfunction. In late pregnancy, alkaline phosphatase can increase to three times ULN, which may persist for several months after delivery, particularly if the mother is breastfeeding, owing to bone effects. In... 

Alkaline phosphatase (ALP) Liver kidney, bone, placenta, intestine, biliary epithelia 30-300 lU/L (higher in children due to increased bone growth) Raised levels may indicate biliary inflammation/ obstruction, malignant infiltration, cirrhosis, bone destruction, Paget s disease... 

Previous work on human alkaline phosphatases has utilized chromatography (ElO) and starch-gel electrophoresis. Thus in 1956 Boman and Westlund (B34) reported the purification and separation of serum phosphatases by Dowex-2 column chromatography. Moss (M34) used gel filtration on Sephadex G-200 and DEAE-celluIose chromatography for separating 5 -nucleotidase and nonspecific alkaline phosphatase activities in human sera. In most of the studies of alkaline phosphatases in human tissues of liver (M33), intestine (M34, M35), bone (M36), kidney (B46), and urine (B44, B46, B47), crude extracts of these tissues were used and... 

In 1961 Nisselbaum et al. (N22) concluded that the major portion of serum alkaline phosphatase was osteogenic in origin because approximately 66% of the alkaline phosphatase in the sera of three normal patients was precipitated by antihuman bone phosphatase sera. This percentage was appreciably higher in five cancer patients (two with liver metastases, two with bone metastases, and one with metastases to both liver and bone). However, the antibone pho hatase serum precipitated liver and kidney alkaline phosphatase as effectively as it did bone. The authors were not willing for other reasons to attribute to kidney and liver a role as tissue sources of serum alkaline phosphatase, but favored bone as the major source. Pelichova et al. have extended the work on intestine (P3). 

Boyer s studies (B39) appear to indicate a lower degree of organ enzyme specificity than that observed by Nisselbaum et al., in that antihuman intestine alkaline phosphatase sera cross-reacted with kidney and placenta. Also, the antihuman bone preparation precipitated alkaline phosphatase from spleen, liver, kidney, and intestine. Boyer considers liver, bone, spleen, and kidney 3-phosphatases to be closely related proteins, followed by intestine and placenta, the enzyme from these latter tissues representing a second and third class of alkaline phosphatase proteins. Intestine and placenta partially cross-react with one another and with a minor kidney component. Three genetic loci are considered by Boyer, therefore, to control the synthesis of alkaline phosphatase. The most recent study in this area is reported by Birkett et al. (B19). 

The greater heat sensitivity of bone alkaline phosphatase as compared to that of liver, kidney, and intestine was first reported without comnaent by Moss and King (M36). The incubation periods (at 55°C and pH 7.0)... 

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. ... 

Alkaline phosphatase (AP orthophosphoric monoester phospho-hydrolase, EC 3.1.3.1) isozymes are present in a wide range of species from bacteria to man and are capable of dephosphorylation and transphosphorylation of a broad spectrum of substrates in vitro [1]. Their broad snbstrate specificity and localization on the outside leaf of the cytoplasmic membrane suggests potential involvement in numerons extracellular processes. In humans, four isozymes of APs have been identified. One of them, tissue-nonspecific alkaline phosphatase (TNAP), is ubiquitously expressed, demonstrating especially high level of expression in bone, liver and kidney tissues. Three other isozymes demonstrate tissue-specific... 

Liver is not the sole source of alkaline phosphatase activity.. Substantial amounts are present in bone, small intestine, placenta and kidney. In normal blood, the alkaline phosphatase activity is derived mainly from bone and liver, with small amounts from intestine. Placental alkaline phosphata.se appears in the maternal blood in the third trimester of pregnancy. Occasionally, the cause of a raised alkaline phosphatase will not be immediately apparent. The liver and bone isoenzymes... 

Alkaline phosphatase (ALP) is present within biliary and canalicular membranes, kidney, intestine, and bone therefore, ALP is not specific for the liver. Plasma alkaline phosphatase (ALP) can be used as a measure of cholestasis (Moss 1982 Schlaeger, Haux, and Katterman 1982), although the high intestinal proportion in the rat and the intra- and intervariability in nonhuman primates reduce its diagnostic value. 

In rats provided with coffee at dilutions of 25,50, or 100% (intake at the 100% level was equivalent to human intake of 37 cups coffee by male rats and 67 cups coffee by female rats) as the sole source of fluid for up to 2 years, elevated levels of cholesterol were observed. A decrease in bone calcium and increase in serum calcium was observed after 1 year but returned to normal without change in treatment. Mean serum alkaline phosphatase, bilirubin, and blood urea nitrogen values were occasionally elevated. Treatment-related increases in relative weights of lungs, kidneys, liver, and epididymides were recorded. An increase in mortality was observed in females receiving 50 or 100% coffee. Levels of tumors were comparable in treatment and control groups (Palm et al. 1984). 

Alkaline phosphatases (ALP) are a group of enzymes found primarily in the liver (isoenzyme ALP-1) and bone (isoenzyme ALP-2). There are also small amounts produced by cells lining the intestines (isoenzyme ALP-3), the placenta, and the kidney (in the proximal convoluted tubules). What is measured in the blood is the total amount of alkaline phosphatase released from these tissues into the blood. As the name implies, this enzyme works best at an alkaline pH (pH 10), and thus the enzyme itself is inactive in the blood. Alkaline phosphatase acts by splitting off phosphorus (an acidic mineral), creating an alkaline pH. The primary importance of measuring alkaline phosphatase is to check the possibility of bone or liver diseases. ... 

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