Alkaline phosphatase isoenzymes

Antithyroid drags have several side effects. The most frequent side effects are maculopapular rashes, pruritus, urticaria, fever, arthralgia and swelling of the joints. They occur in 1-5% of patients [1, 2]. Loss of scalp hair, gastrointestinal problems, elevations of bone isoenzyme of alkaline phosphatase and abnormalities of taste and smell are less common. The incidence of all these untoward reactions is similar with MMI and PTU. Side effects of MMI are dose-related, whereas those of PTU are less clearly related to dose [1]. PTU may cause slight transient increases of serum aminotransferase and y-glutamyl transpeptidase concentrations but also severe hq atotoxicity whereas methimazole or carbimazole can be associated with cholestasis. The side... 

Alkaline phosphatase assays based on 3-glycerophosphate now appears to be obsolete, and methods buffered by either glycine or barbital are also obsolete as these buffers inhibit ALP or are poor buffers. Serum alkaline phosphatase is known to be composed of several isoenzymes which presumably arise from bone, liver, intestine, and placenta. The placental alkaline phosphatase is known to be much more resistant to heat denaturation than the other isoenzymes, and this resistance provides a simple test for it (5). The other enzymes can be separated through the differential inhibition by phenylalanine, by electrophoresis and by specific antibodies. However, the clinical usefulness of the results obtained is in doubt (23). 

Winkelman, J. Nadler, S. Demetrio, J. and Pileggi, V. J. Clinical usefulness of alkaline phosphatase isoenzyme determinations. Am. J. Clin. 

ALP Alkaline phosphatase BM Bone marrow, bowel movement an isoenzyme of... 

Fasting ultrafilterable calcium increased and serum bone alkaline phosphatase isoenzyme levels decreased, but only in those with calcium intakes < 600mg/d. 

Alkaline phosphatases [AP, orthophosphoric-monoester phosphorylase (alkaline optimum) EC 3.1.3.1] represent a large family of almost ubiquitous isoenzymes found in organisms from bacteria to animals. In mammals, there are two forms of AP, one form present in a variety of tissues and another form found only in the intestines. They share common attributes in that the phosphatase activity is optimal at pH 8-10, is activated by the presence of divalent cations, and is inhibited by cysteine, cyanides, arsenate, various metal chelators, and phosphate ions. Most conjugates created with AP utilize the form isolated from calf intestine. 

Ruedl, C., Gstrauntaler, G. and Moser, M. (1989). Differential inhibitory activity of the fungal toxin orellanine on alkaline phosphatase isoenzymes, Biochim. Biophys. Acta, 991, 280-283. 

At-MNDP 31-33, 36, 108), whose mechanism of intracellular localization is related to the presence of oncogenically expressed tumor-membrane alkaline phosphatase isoenzymes 42, 108), has been demonstrated strikingly effective in an animal tumor model 33, 34, 38, 39). It has also served as a concomitant analytical probe for identifying the intracellular locus of radiotherapeutic action of this class of drug by a-particle track autoradiography 33,106-109). Phase I and II human therapeutic trials are shortly envisaged 33, 34). 

Enzymes have different degrees of stability after their collection. Alkaline phosphatase demonstrates up to 10% increased activity after a few hours at room temperature (B15). Most enzymes are not stable at room temperature, but can be preserved in the refrigerator for short periods or in the deep freeze for relatively long times. In Table 4 are tabulated the reported stabilities of many serum enzymes. It must be realized that the problem of enzyme stability is complicated by the fact that the isoenzymes of a particular enzyme may have different stabilities and that specimens with high activities may react differently than those with normal activities (KIO). Although it is indicated in Table 4 that serum... 

Isoenzymes of Human Alkaline Phosphatase William H. Fishman and Nimai K. Ghosh... 

Saleuddin, A. S. M. Isoenzymes of alkaline phosphatase in Anodonta grandis during shell regeneration. Malacologia 9, 501 (1969)... 

Different tissues contain different isoenzymes of alkaline phosphatase, and the intestinal isoenzyme is not inhibited by levamisole The enzyme used in immu-nohistochemistry is extracted from calf intestine, so that levamisole can be used as an inhibitor without affecting the desired reaction. For labile antigens in the intestine, it is better to switch to the peroxidase method. 

The relationship between the various tissue alkaline phosphatases has been under discussion for many years (24). Bodansky established that inhibition by bile acids could be used to distinguish between intestinal and bone or kidney isoenzymes (25). The organ-specific behavior of rat tissue phosphatases toward a variety of compounds was investigated by Fishman (26). Of particular importance was the observation that l-phenylalanine is a stereospecific inhibitor for the intestinal isoenzyme (27). Immunochemical (28, 29) and electrophoretic techniques (30, 31) have shown that there are also physical differences between the tissue phosphatases. It is not yet clear what the precise nature of these differences is (32), although in part it results from a variability in sialic acid content. 

Whyte MP, Landt M, Ryan LM, Mulivor RA, Henthorn PS, Fedde KN, Mahuren JD, Coburn SP. 1995. Alkaline phosphatase placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5 -phosphate. Substrate accumulation in carriers of hypophos-phatasia corrects during pregnancy. J Clin Invest 95 1440-5. 

Isoenzymes or isozymes are enzymes from a single species that have the same kind of enzymatic activity but differ in chemical structure. In addition, they may differ in quantitative characteristics such as possessing different Km s with the same substrate and may differ in response to temperature and effectors. Isozymes of more than 100 enzymes have been demonstrated in humans. The most important of these for diagnostic purposes are the isozymes of LDH, CK, alkaline phosphatase, leucine aminopeptidase, acid phosphatase, and aldolase. These have been exploited for differential organ diagnosis. 

Tsai K-S, Jang M-H, Hsu S H-J, et al. Bone alkaline phosphatase isoenzyme and carboxy-terminal propeptide of type 1 procollagen in healthy Chinese girls and boys. Clin Chem 45 136-138,1999-Wharton B, Bishop N Rickets. Lancet 362 1389-1400, 2003. 

Activity of the cells participating in bone remodeling. Usually it is the activity of the specific enzymes characteristic for the osteoblasts (especially alkaline phosphatase and its bone isoenzyme) or the osteoclasts, respectively (acid phosphatase or its bone isoenzyme)... 

Alkaline phosphatase is an enzyme of the cellular membranes. Its isoforms can be found in liver, digestive tract, placenta, and some tumor tissues. Bone isoform, BALP, is a membrane enzyme of the osteoblasts. Bone, liver, and intestinal isoforms are the posttranslational modifications of the same isoenzyme exprimed by the same gene, and the difference among them lies in various ways of reaction with a saccharide component, sialic acid (M9). 

M9. Moss, D. W., Diagnostic aspects of alkaline phosphatase and its isoenzymes. Clin. Biochem. 20, 225-230 (1987). 

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 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. 

Moss, D.W. Alkaline phosphatase isoenzymes. Clin. Chem. 1982 28 2007-2016... 

The effects on bone metabohsm of carbamazepine, valproate, or phenobarbital as monotherapy have been analysed in a case-control study in 118 ambulatory children with epilepsy and corresponding controls (120). Patients taking carbamazepine or phenobarbital had significantly raised alkaline phosphatase and bone and liver isoenzyme activities compared with controls. Although the authors concluded that children who take anticonvulsants may have their bone metabolism affected, this conclusion was based on abnormal values of a surrogate marker for bone disease. 

Voudris K, Moustaki M, Zeis PM, Dimou S, Vagiakou E, Tsagris B, Skardoutsou A. Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy. Seizure 2002 ll(6) 377-80. 

Intestinal alkaline phosphatase and human tissue non-specific alkaline phosphatase are two urinary isoenzymes that have ehcited interest as potential segment specific markers of the human nephron [190]. Both are members of the closely related group of alkaline phosphatases. Intestinal alkaline phosphatase is the intestinal isoenzyme that is locahzed on the brush border of human intestinal epithelial cells. It is also present in normal human kidney, where it is exclusively expressed on the brush border of tubulo-epithelial cells of the S3-segment of the proximal tubule. The intestinal alkaline phosphatase, which is released in urine, has its origin in the kidney. As a result, intestinal alkaline... 

E614 Gorus, F.K. (1990). Variations in measured alkaline phosphatase activity Influence of isoenzymes and buffer systems. Clin. Chem. 56, 2013-2014. 

EN113 Lee, K.N., Costello, R., Kroll, M. and Elin, R.J. (1992). Comparison of heat inactivation and electrophoresis for evaluating isoenzymes of alkaline phosphatase. Clin. Chem. 38, 984, Abstr. 209. 

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