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)

A repressible alkaline phosphatase has been isolated from the extreme bacterial thermophile. Thermus aquaticus, and has been purified to homogeneity as judged by disc acrylamide electrophoresis and sodium dodecyl sulfate electrophoresis. Upon investigation, the purified enzyme was shown to hydrolyze certain phosphodiesters in addition to a wide variety of phosphomonoesters. The diesters included bis-p-nitro-phenyl phosphate and thymidine 3'-monophospho-p-nitro-phenyl ester. The temperature optimum for the diesterase activity was 80--85 degrees at pH 7.2. Orthophosphate competitively inhibited both activities. Nucleotides such as AMP, ADP, and ATP also inhibited both esterase activities as did alpha-D-glucose 1-phosphate and alpha-sodium glycerol phosphate. The isoelectric point of the enzyme was determined to be 8.4.
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PMID:Repressible alkaline phosphatase from Thermus aquaticus: associated phosphodiesterase activity. 1

1. The kinetics of the hydrolysis of nitrophenylphosphate by nonspecific acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2.) from Schizosaccharomices pombe was studied. 2. The kinetic parameters, Km and V, were determined as well as the inhibition constants, K1, for the inhibitors, phosphate and fluoride, as a function of pH. 3. The results, interpreted according to the theories of Dixon and Waley indicated the presence of three ionizable groups on the enzyme itself and one on the enzyme-substrate complex. 4. A model of the hydrolysis of phosphoric acid monoesters by the S. pombe acid phosphatase is proposed based on the ionization state of the reactants and on the results of the inhibition by the competitive inhibitors.
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PMID:Some kinetic aspects of the mechanism of hydrolysis of phosphoric acid esters by nonspecific acid phosphatase from Schizosaccharomyces pombe. 2 60

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
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PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

25.6% of 254 epileptic children receiving anticonvulsant drugs more than 3 years showed disturbances of Calcium-phosphate-metabolism and of ossification respectively. These disturbances are divided into 4 degrees of severity: 1. Raised alkaline phosphatase in serum alone 21 patients); 2. Metaphysial osteodystrophia (22 Pat.); 3. Generalised osteoporosis (16 Pat.) and 4. Vitamin-D sensitive rickets (6 Pat.). These abnormalities were found at most in long term-treatment with hydantoins or primidone. The measurement of serum concentration of these anticonvulsant drugs yielded significantly higher amounts in patients with abnormalities in Calcium-Phosphate-metabolism than in those patients without such ones. This result permits us to conclude that disturbances of Calcium-Phosphate-metabolism are serum-concentration-dependent side-effects of anticonvulsant drugs.
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PMID:[Disturbances of calcium-phosphate-metabolism by anticonvulsant drugs in relation to their serum concentration (author's transl)]. 10 36

Either vitamin D3 (or 1 alpha,25--(OH)2-D3) or hydrocortisone (HC) stimulated phosphate accumulation by organ-cultured embryonic chick duodenum. In combination, these two steroids stimulated phosphate uptake synergistically. Phosphate accumulation appeared to be independent of other vitamin D3-stimulated processes: CaBP concentration, cAMP concentration, or alkaline phosphatase activity. L-phenylalanine, a reported alkaline phosphatase inhibitor, when added to the culture medium progressively inhibited either D3- or HC-stimulated phosphate uptake subsequent to culture, but did not inhibit the synergistic action. Under these conditions L-phenylalanine had no consistent effect on alkaline phosphatase activity but unexpectedly, greatly inhibited vitamin D3-stimulated CaBP concentration, but only in the absence of HC. Some limited suggestion of an intestinal phosphoprotein sensitive to either vitamin D3 or HC was observed.
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PMID:Hydrocortisone and vitamin D3 stimulation of 32Pi-phosphate accumulation by organ-cultured chick embryo duodenum. 22 77

The phosphorus contents of acid-soluble pools, lipid, ribonucleic acid, and acid-insoluble polyphosphate were lowered in Synechococcus in proportion to the reduction in growth rate in phosphate-limited but not in nitrate-limited continuous culture. Phosphorus in these cell fractions was lost proportionately during progressive phosphate starvation of batch cultures. Acid-insoluble polyphosphate was always present in all cultural conditions to about 10% of total cell phosphorus and did not turn over during balanced exponential growth. Extensive polyphosphate formation occurred transiently when phosphate was given to cells which had been phosphate limited. This material was broken down after 8 h even in the presence of excess external orthophosphate, and its phosphorus was transferred into other cell fractions, notably ribonucleic acid. Phosphate uptake kinetics indicated an invariant apparent K(m) of about 0.5 muM, but V(max) was 40 to 50 times greater in cells from phosphate-limited cultures than in cells from nitrate-limited or balanced batch cultures. Over 90% of the phosphate taken up within the first 30 s at 15 degrees C was recovered as orthophosphate. The uptake process is highly specific, since neither phosphate entry nor growth was affected by a 100-fold excess of arsenate. The activity of polyphosphate synthetase in cell extracts increased at least 20-fold during phosphate starvation or in phosphate-restricted growth, but polyphosphatase activity was little changed by different growth conditions. The findings suggest that derepression of the phosphate transport and polyphosphate-synthesizing systems as well as alkaline phosphatase occurs in phosphate shortage, but that the breakdown of polyphosphate in this organism is regulated by modulation of existing enzyme activity.
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PMID:Regulation of phosphate accumulation in the unicellular cyanobacterium Synechococcus. 22 42

The interaction of a fluorinated phosphonate with Zn-2+-and Mn-2+-alkaline phosphatase as studied by 19-F NMR revealed a stoichiometry of 1:1 for the binding of the phosphonate anion to the enzyme. In the presence of two metal ions, one fluorinated phosphonate ion was found to interact strongly with the enzyme, while a different interaction was observed when the number of metal ions per enzyme exceeded two. Phosphate replaced enzyme bound phosphonate, as is shown by the 19-F NMR spectra. No direct interaction between the fluorinated phosphonate and the metal ion responsible for enzyme activity was indicated by the 19-F NMR data. This observation supports the idea of a considerable distance between metal ion and substrate binding site in Escherichia coli alkaline phosphatase.
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PMID:19-F NMR studies of the binding of a fluorine-labeled phosphonate ion to E. coli alkaline phosphatase. 23 75

Phosphate-water oxygen exchange catalyzed by Escherichia coli alkaline phosphatase was monitored using the 18O shift on the 31P NMR signal of inorganic phosphate. Different kinetic patterns were observed with native zinc enzyme and with its cobalt analogue. For native enzyme at pH values ranging from 4.4 to 10.0, the distribution of 18O species in Pi, viz. P18O4, P18O316O,P18O216O2,P18O16O3,P16O4, with time is compatible with a kinetic scheme in which E-P, the noncovalent enzyme-phosphate complex, dissociates more rapidly than it forms the covalent complex E-P. For the cobalt enzyme at pH 6.8, the distribution of 18O species in Pi with time is different and leads to the conclusion that formation of E-P is more rapid than dissociation of Pi from E-P-A computer simulation gave good quantitative agreement with the observed distribution for the time course of the cobalt enzyme reaction when the ratio of the rate of formation of E-P to dissection of E-P was assumed to be 3 +/- 0.5.
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PMID:Metal dependence of the phosphate (oxygen)-water exchange reaction of Escherichia coli alkaline phosphatase. Kinetics followed by 31P(18O) NMR. 35 Aug 68

Orthovanadate was shown to be a potent competitive inhibitor (Ki less than 1 microM) of purified alkaline phosphatase from human liver, intestine of kidney. Inhibition was reversed and full enzymic activity restored in the presence of 1mM-adrenaline. Phosphate and vanadate competed for the same binding site on the enzyme.
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PMID:Inhibition of human alkaline phosphatases by vanadate. 48 56

Squamous cell carcinomas were induced in the hamster cheek pouch with 9,10-dimethyl-1,2-benzanthracene. The process of carcinogenesis was inhibited by phenylphosphate, an inducer of alkaline phosphatase. Orthophosphate and l-phenylalanine, which inhibit alkaline phosphatase, had a promoting effect on tumor formation. The results are in accordance with those of previous studies on the effect of inducers of alkaline phosphatase on chemical carcinogenesis. The effect of the studied substances on carcinogenesis was apparently unrelated to the presence of phenyl or phosphate groups or of steroid rings. The tumor inhibition or promotion seemed to be related to the potential of the tested substances to induce or inhibit alkaline phosphatase activity.
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PMID:Chemical carcinogenesis in the hamster cheek pouch. Influence of inhibitors and inducers of alkaline phosphatase. 81 3


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