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)

O,O,S-Trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl damage the type I pneumocytes of the alveolar epithelium in rats. Butylated hydroxytoluene causes similar damage in mice. The toxicity of these compounds is dependent on their bioactivation by the cytochrome P-450 (CYP) system. A range of compounds, that modifies the activity of specific CYP isoenzymes, has been used to establish those particular isoenzymes involved in bioactivation. Pulmonary toxicity was assessed by measurement of lung weight and changes in the activity of gamma-glutamyltranspeptidase and alkaline phosphatase in bronchoalveolar lavage fluid. O,O,S-Trimethylphosphorodithioate, bromophos, p-xylene and 2,4-dichloro-(6-phenyl-phenoxy)ethylamine all inhibited the dealkylation of pentoxyresorufin, an indicator of CYP2B1 activity, and also prevented pulmonary toxicity. There was a significant negative correlation between the level of pulmonary pentoxyresorufin dealkylation after pretreatment with O,O,S-trimethylphosphorodithioate and the severity of lung injury. This pretreatment also reduced the toxicity of butylated hydroxytoluene by a factor of 20 and methylcyclopentadienyl manganese tricarbonyl by a factor of 10. Modification of the activity of CYP1A1, CYP2E1 and CYP4B1 did not alter the toxicity of these compounds. These results indicate that pulmonary CYP2B1 is responsible for the bioactivation and toxicity of O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl in rats and the orthologous 2B isoenzyme in mice activates butylated hydroxytoluene.
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PMID:Cytochrome P450 2B isoenzymes are responsible for the pulmonary bioactivation and toxicity of butylated hydroxytoluene, O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl. 835 17

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 mumol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 mumol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occurred at the 50 mumol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 mumol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%-137.5%) than the 50 mumol/mL formulation (46.2%-86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP--enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 mumol/kg Mn-DPDP at a concentration of 10 mumol/mL is safe and efficient enough to proceed to further clinical trials.
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PMID:Mn-DPDP-enhanced MR imaging of malignant liver lesions: efficacy and safety in 20 patients. 840 May 58

Temperature-labile cholesterol ester hydrolase (TLCEH) was purified 2,000-fold from rat testis cytosol using sequential ammonium sulfate precipitation, cation exchange chromatography, and isoelectric focusing chromatography. the purified enzyme, which exhibited a single silver-stained band (66 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was inhibited 89% by the elevation of the temperature from 32 to 37 degrees C and 65% by treatment with alkaline phosphatase. Its amino acid composition and amino-terminal sequence differed markedly from those of isoenzymes from other tissues, although 6 of 20 residues were conserved. Polyclonal antibodies raised to TLCEH exhibited no cross-immunoreactivity with cytosolic proteins from other rat tissues and inhibited 70% of testis cytosolic CEH. Western blot analysis demonstrated a high correlation between immunoreactive protein and catalytic activity in the testis during maturation of the rat, with a marked increase at the onset of spermatogenesis. TLCEH was inhibited by physiological levels of Cu2+ (I50 = 0.60 microM) and Zn2+ (I50 = 0.75 microM) and by Cd2+ (I50 = 0.15 microM) but not by 0.5-5 mM Mn2+.
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PMID:Testicular temperature-labile cholesteryl ester hydrolase. Relationship to isoenzymes from other tissues, correlation with spermatogenesis, and inhibition by physiological concentrations of divalent cations. 846 27

Acid and neutral trehalase activities (optimum pH of 4.6 and 6.8, respectively) from Fusarium oxysporum var. lini were studied separately through partial isolation by ammonium sulfate precipitation followed by ion-exchange chromatography on DEAE-Sephacel for neutral enzyme, or using some of their differential properties. Acid activity was unaffected by 1 mM of Ca2+, Mg2+, Mn2+, Ba2+, or EDTA. Contrarily, the neutral enzyme was activated by Ca2+ with an apparent Ka of 0.15 mM; was inhibited by EDTA, Zn2+, Hg2+, or Mg(2+)-ATP; and showed an increase in activity by the raise of buffer ionic strength or by the addition of 100 mM KCl. Acid and neutral enzymes have, respectively, an apparent optimum temperature of 45 and 30 degrees C, an apparent Km for trehalose of 0.43 and 8.45 mM, and an apparent M(r) of 160,000 and 100,000 (by glycerol gradient ultracentrifugation). Acid trehalase was specifically inhibited by acetate buffer and more stable at 50 degrees C than the neutral enzyme. Neutral enzyme exhibited a pI of 6.2 by isoelectric focusing. Contrary to neutral trehalases from other fungi, the enzyme from Fusarium oxysporum var. lini was not activated in crude extract by treatment with Mg(2+)-ATP in the presence of cAMP and not inactivated by alkaline phosphatase from Escherichia coli.
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PMID:Comparative study of two trehalase activities from Fusarium oxysporum var. lini. 854 49

A gene (phoV) encoding an alkaline phosphatase from Synechococcus sp. strain PCC 7942 was isolated by screening a plasmid gene bank for expression of alkaline phosphatase activity in Escherichia coli JM103. Two independent clones carrying the same alkaline-phosphatase-encoding gene were isolated. One of these clones (pKW1) was further analysed and the nucleotide sequence of a contiguous 3234 bp DNA fragment was determined. Two complete open reading frames (ORF1 and phoV) and an incomplete ORF3 were identified reading in the same direction. The deduced phoV gene product showed 34% identity to the alkaline phosphatase PhoA from Zymomonas mobilis, and the N-terminal part of the putative ORF3 protein exhibited 57% identity to a protein of unknown function from Frankia sp. Insertional inactivation of the Synechococcus PCC 7942 phoV gene failed, indicating an essential role for either the phoV or the ORF3 gene product. PhoV consists of 550 amino acid residues, resulting in a molecular mass of 61.3 kDa. To overexpress the Synechococcus PCC 7942 phoV gene in E. coli, plasmid pKW1 was transformed into a phoA mutant of E. coli (CC118). In E. coli strain CC118(pKW1) PhoV was expressed constitutively with high rates of activity, and was shown to be membrane associated in the periplasmic space. After partial purification of the recombinant PhoV, it was shown that, like other alkaline phosphatases, the Synechococcus PhoV had a broad pH optimum in the alkaline region and a broad substrate specificity for phosphomonoesters, required Zn2+ for activity, and was inhibited by phosphate. In contrast to several other alkaline phosphatases, PhoV was inhibited by Mn2+. Due to the lack of a Synechococcus PCC 7942 phoV mutant strain, the function of PhoV remains uncertain. However, the present results show that Synechococcus PCC 7942 has a second, probably phosphate-irrepressible, alkaline phosphatase (PhoV, 61.3 kDa) in addition to the phosphate-repressible enzyme (PhoA, 145 kDa) already described.
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PMID:The cyanobacterium Synechococcus sp. strain PCC 7942 contains a second alkaline phosphatase encoded by phoV. 857 98

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the alpha 4 integrins alpha 4 beta 1 (very late antigen 4: VLA4) and alpha 4 beta 7, which are constitutively expressed on many leukocyte subsets and play a key role in cell trafficking and activation. Using a recombinant VCAM-IgG fusion protein (VCAM-Ig) as a soluble ligand for alpha 4 beta 1 we directly demonstrated by fluorescence analysis that the alpha 4 beta 1 receptor can exist in different affinity states on the cell surface, and that a high affinity state is induced by manganese ions or certain activating anti-beta 1 monoclonal antibodies (Jakubowski et al., 1995b). Here we have extended these observations by developing a rapid and reproducible assay using alkaline phosphatase (AP)-coupled VCAM-Ig (VCAM-Ig-AP) which measures the interaction between VCAM1 and alpha 4 integrins in a microtiter plate format. This assay has allowed us to evaluate directly the effects of metal ions, anti-beta 1 mAbs, and different cell types and species on the VCAM1/alpha 4 integrin interaction. Most importantly, the assay system provides a means to rapidly evaluate alpha 4 integrin-directed inhibitors without the complication of post-ligand binding events inherent in adhesion assays.
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PMID:A direct binding assay for the vascular cell adhesion molecule-1 (VCAM1) interaction with alpha 4 integrins. 864 Mar 76

The effect of essential trace metals on bone metabolism was investigated in the femoral-metaphyseal tissues obtained from skeletal-unloaded rats. Skeletal unloading was designed by using the model of hindlimb suspension in rats; the animals were fed for 4 days with the unloading. Femoral-metaphyseal tissues were cultured for 24 hours in a medium containing either vehicle (control), nickel, manganese, cobalt, copper, zinc, or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; AHZ) in the concentration range of 10(-6) to 10(-4) M. Bone biochemical components (alkaline phosphatase activity, glucose consumption, and DNA content) were significantly decreased by skeletal unloading. The presence of zinc sulfate or AHZ (10(-5) and 10(-4) M) caused a significant increase of alkaline phosphatase activity in the bone tissues from unloaded rats. This effect was not seen by nickel, manganese, cobalt and copper (10(-6) to 10(-4) M). The culture medium glucose was clearly consumed by the bone tissues. This consumption was inhibited by nickel, manganese, or copper (10(-5) and 10(-4) M), while cobalt, zinc, and AHZ had no effect. DNA content in the bone tissues from unloaded rats was significantly increased by all metal compounds (10(-5) M). The effect of AHZ on bone components was greater than zinc sulfate. The AHZ (10(-5) M)-increased alkaline phosphatase activity in the bone tissues from unloaded rats was clearly blocked by the presence of cycloheximide (10(-6) M), staurosporine (10(-7) M), dibucaine (10(-4) M), or okadaic acid (10(-7) M). The present study demonstrates that, of various essential trace metals, zinc compounds have an unique anabolic effect on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading. Zinc-chelating dipeptide may stimulate bone protein synthesis through the mechanism that is involved in protein kinases.
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PMID:Effect of essential trace metal on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading: comparison with zinc-chelating dipeptide. 866 81

Three groups of individually housed albino rats (n = 6, initial average weight = 47 g) were fed diets based on egg white and cornstarch (basal diet 8 g Ca, 5.2 g P, 0.76 g Mg, 100 mg Zn, 100 mg Fe, 50 mg Mn, 7 mg Cu, and 5 mg Cd per kilogram diet) over a 4-week period. Group I (controls) was fed the basal diet free of phytic acid (PA) and microbial phytase. In groups II and III cornstarch was replaced by 0.5% PA from NaPA (molar PA/Zn ratio approximately 5). In group III, 2,000 U of microbial phytase from Aspergillus niger per kilogram diet was added. Live weight gain, zinc status (zinc in plasma, femur, liver, and testes; activity of the plasma alkaline phosphatase), and apparent absorption of zinc, iron, copper, and manganese remained unchanged by the different dietary treatments. The apparent phosphorus absorption was highest in the phytase group. PA decreased and microbial phytase improved the apparent absorption of calcium and magnesium. Liver cadmium concentration, total liver and kidney cadmium content, as well as fractional liver and kidney cadmium accumulation in rats fed the diet containing PA were significantly higher than those in the controls. Phytase supplementation lowered liver and kidney cadmium accumulation. Differences in calcium and magnesium bioavailability due to PA and microbial phytase may be one factor in the alteration of tissue cadmium accumulation.
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PMID:Effect of phytic acid and microbial phytase on Cd accumulation, Zn status, and apparent absorption of Ca, P, Mg, Fe, Zn, Cu, and Mn in growing rats. 867 72

Alkaline phosphatase activity was released up to 100% from the membrane by incubating the rat osseous plate membrane-bound enzyme with phosphatidylinositol-specific phospholipase C. The molecular weight of the released enzyme was 145,000 on Sephacryl S-300 gel filtration and 66,000 on PAGE-SDS, suggesting a dimeric structure. Solubilization of the membrane-bound enzyme with phospholipase C did not destroy its ability to hydrolyse PNPP, ATP and pyrophosphate. The hydrolysis of ATP and PNPP by phosphatidylinositol-specific phospholipase C-released enzyme exhibited 'Michaelian' kinetics with K0.5 = 70 and 979 microM, respectively. For pyrophosphate, K0.5 was 128 microM and site-site interactions were observed (n = 1.4). Magnesium ions were stimulatory (K0.5 = 1.5 mM) and zinc ions were a powerful noncompetitive inhibitor (Ki = 6.2 microM) of phosphatidylinositol-specific phospholipase C-released enzyme. Phosphatidylinositol-specific phospholipase C-released alkaline phosphatase was relatively stable at 40 degrees C. However, with increasing temperature from 40-60 degrees C, the enzyme was inactivated rapidly following first order kinetics and thermal inactivation constants varied from 5.08 x 10(-4) min-1 to 0.684 min-1. Treatment of phosphatydilinositol-specific phospholipase C-released alkaline phosphatase with Chellex 100 depleted to 5% its original PNPPase activity. Magnesium (K0.5 = 29.5 microM), manganese (K0.5 = 5 microM) and cobalt ions (K0.5 = 10.1 microM) restored the activity of Chelex-treated enzyme, demonstrating its metalloenzyme nature. The stimulation of Chelex-treated enzyme by calcium ions (K0.5 = 653 microM) was less effective (only 26%) and occurred with site-site interactions (n = 0.7). Zinc ions had no stimulatory effects. The possibility that the soluble form of the enzyme, detected during endochondral ossification, would arise by the hydrolysis of the Pl-anchored form of osseous plate alkaline phosphatase is discussed.
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PMID:Characterization of the phosphatidylinositol-specific phospholipase C-released form of rat osseous plate alkaline phosphatase and its possible significance on endochondral ossification. 875 Nov 58

The objective of this study was to determine the concentration of Zinc (Zn), Copper (Cu) and Manganese (Mn) in hepatic tissue from extrahepatic biliary atresia (EHBA). Liver biopsy samples were obtained at time of portoenterostomy from 49 infants ages 1.1 to 20.7 months (median 2.1) with EHBA. Samples were dry ashed and analyzed by flame (Zn) or flameless (Cu and Mn) atomic absorption spectrophotometry. Hepatic Cu concentrations are physiologically elevated at birth and decline rapidly during the first 2 month of life, therefore only samples from 29 infants, ages greater than 8 weeks were considered for Cu. Concentrations (mg/kg dry weight, mean and range) were: Zn 142 (70-507), Cu 204 (19-570), Mn 9.1 (2.8-21.8) vs. literature controls in the same age range: Zn 262 (82-543), Cu 92, Mn 4.3 (3.3-11.5). No correlations were found between serum alkaline phosphatase, AST or total bilirubin and hepatic trace element concentrations, between trace element concentrations and age, or between Cu and Mn. Decreased bile flow with intrahepatic cholestasis may result in hepatic accumulation of Mn as well as Cu. The low hepatic Zn concentrations indicate the need for further study of Zn metabolism in this population.
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PMID:Hepatic concentrations of zinc, copper and manganese in infants with extrahepatic biliary atresia. 884 56


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