Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroglobulin (TG), the major exportable protein of thyroid follicle cells, is conveyed to lysosomes on a complex secretion, storage and recapture pathway by as yet unknown transport mechanisms. This report establishes that the dimeric porcine TG-molecule carries an average of six phosphate residues. Endoglycosidase digestion showed that two phosphate residues are bound to the high-mannose carbohydrate side chains (CHO), while two others are linked to the complex CHO. These four residues are also sensitive to alkaline phosphatase treatment, indicating their terminal linkage. Immunoprecipitation analyses showed that TG obtained from microsomal fractions is already phosphorylated. Most important, an enzymatic assay applied to hydrolysates of TG established that the two phosphate residues at the high mannose CHO are present as mannose-6-phosphate (M-6-P). Alkaline phosphatase treatment of biosynthetically radiophosphorylated CHO followed by hydrolysis and t.l.c. indicated that M-6-P is present at least in part in phosphomonoester linkage. Furthermore, porcine TG binds specifically to the M-6-P receptor of Chinese hamster ovary cells. It is concluded that the M-6-P residues of TG are exposed and able to operate as a ligand for the M-6-P receptor. It is unknown why the lysosomal recognition-marker M-6-P does not convey TG directly on an intracellular route to lysosomes. We propose that for the secretion of newly synthesized TG into the follicle lumen an additional export signal dominating over the M-6-P recognition-marker is required.
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PMID:Thyroglobulin, the major and obligatory exportable protein of thyroid follicle cells, carries the lysosomal recognition marker mannose-6-phosphate. 358 67

Mouse bone marrow-derived mast cells passively sensitized with monoclonal IgE released paf-acether (platelet-activating factor) and beta-hexosaminidase when challenged with the specific antigen. The formation and the release of paf-acether followed an early increase in the activity of the acetyltransferase, the main enzyme in paf-acether biosynthesis. The antigen-induced activation of the acetyltransferase was dependent on physiologic temperature and on the presence of Ca2+. By using microsomal fractions from unchallenged and challenged mast cells, the Vmax values were 3.5 and 12.0 nmol/min/mg of protein, respectively, whereas in both cases a Km value for acetyl-coenzyme A of 172 microM was measured. The stimulation of acetyltransferase could be mimicked in vitro under experimental conditions which favor phosphorylation, i.e. adding ATP and Mg2+ to lysates from unchallenged mast cells. In contrast, ATP and Mg2+ were uneffective on lysates from challenged cells that exhibited high level of acetyltransferase activity, suggesting that phosphorylation of the enzyme already took place at the time of cell stimulation. Moreover, addition of alkaline phosphatase to microsomal fraction obtained from either antigen-challenged mouse bone marrow-derived mast cells or unchallenged cells, resulted in 52% and 43% loss of acetyltransferase activity, respectively. Phorbol myristate acetate treatment of cells doubled the enzyme activity supporting the phosphorylation hypothesis. Thus, we report on the immunologic activation of a key enzyme for paf-acether synthesis and on the mechanism of this activation in a pure mast cell population. A link between bridging of IgE receptors and the activation of an enzyme critical to the formation of a lipid mediator is thereby evidenced.
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PMID:Biosynthesis of paf-acether. IX. Role for a phosphorylation-dependent activation of acetyltransferase in antigen-stimulated mouse mast cells. 358 83

Alkaline phosphatase activity in the liver and intestine increases after bile duct ligation, reportedly by increased enzyme synthesis. To ascertain the mechanism of this increased synthesis in the absence of a cDNA clone encoding the enzyme, we have estimated the concentration of liver and intestinal alkaline phosphatase mRNA by translational analysis. Monospecific antiserum to rat placental alkaline phosphatase was raised. The resulting antiserum precipitated two peptides of 53 and 56 kd after translation of liver poly(A) + RNA. The precipitation of both peptides was blocked by the single 64 kd placental alkaline phosphatase. Processing of the cell-free products by microsomal membranes produced peptides of 62 and 64 kd. Antiserum to rat intestinal alkaline phosphatase also identified two peptides as products of intestinal RNA translation. After bile duct ligation, we confirmed a transient 2-fold increase in alkaline phosphatase activity in the intestine and a more constant 7-fold increase in the liver. However, the alkaline phosphatase mRNA concentration remained unchanged in both organs. We conclude that increased alkaline phosphatase synthesis after bile duct ligation results from an enhanced rate of translation of mRNA.
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PMID:The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat. 371 Apr 26

The rat brains homogenized with different media (sucrose, ethylene glycol, dimethyl sulfoxide and urea) yielded different amounts of microsomal fractions. The dielectric constant, density and viscosity of the homogenization media did not correlate with the amount of microsomes separated by differential centrifugation. The homogenization media containing dimethyl sulfoxide were the most efficient for the isolation of rat brain microsomes. The increase in the yield was up to 4-fold when 50% (v/v) dimethyl sulfoxide was employed. Microsomes isolated in this manner were analogous to those obtained from isotonic sucrose solution, as was demonstrated by their chemical and enzymatic (5'-nucleotidase, adenosine deaminase, guanine deaminase, purine-nucleoside phosphorylase, lactate, malate and glutamate dehydrogenases, amine oxidase fumarate hydratase, acid and alkaline phosphatase, acetylcholinesterase, NADPH-cytochrome c reductase, catalase and thiamine-diphosphatase) characterization.
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PMID:An improved method for the preparation of rat brain microsomes. 371 74

Common bile duct ligation (CBDL) in rats was used to induce liver disease and secondary kidney damage. The biochemical changes in the liver, kidney and plasma were studied at 3, 6, 10 and 21 days post CBDL. The observed alterations climaxed at the 6th day following ligation. Renal, activities of aldolase (ALD), lactic dehydrogenase (LDH), isocitric dehydrogenase (ICDH), sorbitol dehydrogenase (SDH), and alkaline phosphatase (ALP), were lowered in CBDL rats. Further, microsomal Na,K-ATPase and Mg-ATPase and mitochondrial oxidative-phosphorylation were inhibited. In the liver from CBDL rats the activities of aspartate aminotransferase (AST), Mg-ATPase and ALP were elevated, while SDH, ALD, malic dehydrogenase (MDH), LDH, malic enzyme (ME) and Na,K-ATPase were lowered. Plasma enzymes, AST, ALP, MDH, LDH, ALD, acid phosphatase (ACP) and ICDH and the metabolites bile acids, bilirubin, creatinine and urea were elevated. Addition of bile acids or bilirubin at concentrations comparable to those found in the plasma of CBDL rats, to the reaction mixture of the various enzymes strongly inhibited most, particularly mitochondrial oxidative phosphorylation. High concentrations of these substances in the blood may explain the development of renal failure during liver disease and its reversibility when liver function returns to normal.
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PMID:Biochemical changes in liver, kidney and blood associated with common bile duct ligation. 378 11

Residues of the insecticidal mixture, toxaphene, have been found in Great Lakes fish. The purpose of the present study was to assess the subchronic toxicity of toxaphene in the rat and beagle dog. In the rat study, groups of 10 male and 10 female animals were fed diets containing 0, 4, 20, 100, or 500 ppm of the test compound for 13 weeks. No clinical signs of toxicity or spontaneous deaths were observed. Toxaphene treatment up to 500 ppm had no effects on weight gain or food consumption. The liver/body weight ratio and hepatic microsomal enzyme activities (phenobarbital type) were increased in both sexes fed 500 ppm of the test compound. Toxaphene at the highest dose also caused kidney enlargement in male but not in female rats. Dose-dependent histological changes were seen in the kidney, thyroid, and liver. Changes in the liver and thyroid were considered to be adaptative but the injury in the proximal tubules of the kidney was focally severe. Groups of six male and six female beagle dogs were fed toxaphene in gelatin capsules at 0, 0.2, 2.0, and 5.0 mg/kg body wt/kg body wt/day for 13 weeks. Food consumption and growth rate were not affected. All animals survived the entire treatment period. No clinical signs of toxicity were observed. The liver/body weight ratio and serum alkaline phosphatase were increased in dogs of both sexes fed 5.0 mg/kg. Mild to moderate dose-dependent histological changes were observed in the liver and thyroid. Toxaphene was accumulated in a dose-dependent manner in the fat and liver of dogs and rats. Based on the biochemical, histological, and residue data, it was concluded that the no-adverse-effect levels of the pesticide were 4.0 ppm (0.35 mg/kg) for the rat and 0.2 mg/kg for the dog.
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PMID:Toxicity of toxaphene in the rat and beagle dog. 378 Nov 30

The synergistic hepatotoxicity of dietary disulfiram (DSF) with 1,2-dichloroethane (DCE) subchronically administered by inhalation at three concentration levels (150, 300, and 450 ppm) was studied. The criteria for hepatotoxicity were treatment-related increases in serum activities of sorbitol dehydrogenase, 5'-nucleotidase, and alkaline phosphatase, and in liver-to-body weight ratios. DSF alone did not elicit these responses while DCE at the highest concentration level increased liver-to-body weight ratios and the activity of 5'-nucleotidase. Exposure to DSF alone decreased cytochrome P450 levels, but in combination with DCE, the decrement of cytochrome P450 was additive in a DCE concentration-dependent manner. However, depression of cytochrome P450 by DCE alone was not concentration dependent. Although DSF and DSF/DCE combination increased the activity of glutathione S-transferases (GSTs), both DSF and DCE singly and in combination increased the tissue levels of reduced glutathione (GSH). Evidence is presented showing that the potentiation of the hepatotoxicity of DCE observed in the presence of DSF may be due to an inhibition of microsomal mixed-function oxidase-mediated metabolism of DCE and to a compensatory increase in DCE metabolism to reactive metabolites generated by GST-mediated conjugation of DCE with GSH.
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PMID:Interaction between 1,2-dichloroethane and tetraethylthiuram disulfide (disulfiram). II. Hepatotoxic manifestations with possible mechanism of action. 378 26

The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine. Recently, caffeine clearance in saliva has been studied extensively in this laboratory, and, on the basis of a constant relationship between caffeine concentrations in serum and saliva, overnight clearance measurements (requiring a saliva sample at bedtime and upon arising following a single oral dose of caffeine) have been shown to be closely related to ABT or GEC. This approach, which has been successfully used in children, may represent the first simple and innocuous test for quantifying of hepatic function in the pediatric age group. The clinical utility of these clearance tests is to assess severity of disease (or genetically determined impairment of function), thus yielding important clues to prognosis.
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PMID:[Foreign substances as indicators of liver function]. 386 35

About 80% of the total activity of the alkaline phosphatase of the calf intestine was found within the lumen and only 20% in the mucosa. The specific activity of the intralumenal enzyme fraction was about ten times higher than that of the mucosa enzyme. Differential centrifugation experiments demonstrated that the intralumenal enzyme of the proximal gut segment can be found in a fraction which exhibits sedimentation behaviour like a microsomal fraction, whilst the intralumenal enzyme of the distal gut segment was found to be soluble in the supernatant after centrifugation at 135000 X g for 60 min. Ouchterlony double diffusion analysis and antibody inhibition of alkaline phosphatase by antisera against the mucosa enzyme demonstrate that the two forms of intestinal enzyme have apparently identical antigenicity. Purified alkaline phosphatase obtained from the intralumenal fraction and from mucosa exhibits closely related pH-optima, Michaelis constants, amino acid inhibition type and inhibition constants. The results of large scale release of alkaline phosphatase bound to microvesicles are discussed with regard to results of morphological investigations in different tissues and cell cultures demonstrating the formation of intestinal membrane bodies and cell extrusion.
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PMID:Intralumenal alkaline phosphatase of the calf intestine. 392 37

The aim of this study was to investigate possible mechanisms involved in the elevation of serum alkaline phosphatase activity in alcoholics. Male Sprague-Dawley rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 4-5 wk. Serum alkaline phosphatase activity was increased moderately but significantly. Hepatocytes isolated from ethanol-fed animals exhibited pronounced morphologic alterations of their plasma membranes by scanning electron microscopy and a reduced content of alkaline phosphatase despite an increase in total liver alkaline phosphatase content. Chronic ethanol feeding also potentiated the release of alkaline phosphatase from the cells during incubation with 50 mM ethanol. Furthermore, chronic ethanol feeding resulted in reduced recovery of alkaline phosphatase in hepatic plasma membranes isolated by sucrose gradient centrifugation but did not affect the recoveries of other plasma membrane markers (5'-nucleotidase and Na+,K+-adenosine triphosphatase) nor the subcellular distribution of alkaline phosphatase in the nuclear, mitochondrial, microsomal, and cytosolic fractions. These findings suggest that the increased serum alkaline phosphatase levels observed in response to chronic ethanol feeding may be due, at least in part, to increased lability of this plasma membrane enzyme.
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PMID:Chronic ethanol consumption alters rat liver plasma membranes and potentiates release of alkaline phosphatase. 403 95


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