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)

Human liver alkaline phosphatase is a metalloenzyme requiring Zn2 and Mg2 for full activity. Zn2 cannot be replaced by manganese, cobalt or calcium, whereas Mg2 can be replaced by manganese or calcium. The binding constants of the enzyme for different divalent cations were determined by the use of complexing agents. The enzyme is inhibited by a number of reducing and complexing agents such as 2-mercaptoethanol, cyanide, nitrilotriacetic acid and EDTA. From studies using these inhibitors it is suggested that there are different mechanisms of inhibition. Reversible inhibition occurs if the free Zn2 concentration is not significantly lower than 10(-12)M. Inhibition is irreversible at lower Zn2 concentrations. Evidence is given, that the human liver alkaline phosphatase possesses different zinc binding sites, which are responsible for the catalytic function and for the integrity of the enzyme structure.
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PMID:Human alkaline phosphatases. II. Metalloenzyme properties of the enzyme from human liver. 92 71

In a previous paper we reported that serum, urine and fecal zinc levels fell markedly in women taking a combination oral contraceptive agent (+OCA) and in women with normal menstrual cycles (-OCA) when they consumed a low-zinc diet (less than 0.2 mg/day) for 35 days. We evaluated other biochemical and clinical data in order to determine if depletion of accessible body zinc and/or physiologic adjustment to conserve body zinc stores had occurred. Neither low zinc intake nor oral contraceptive use appeared to influence nitrogen balance or body weight. Use of contraceptive drugs appeared to influence the response of blood parameters to zinc depletion. Serum transferrin and cholesterol declined significantly in the -OCA group, whereas alkaline phosphatase and gamma-globulin changed significantly in both groups. Clinical problems developed in all the subjects with serum zinc levels below 50 microgram/dl during the study; three of the six with serum zinc levels above 50 microgram/dl also complained of clinical symptoms. The results suggest that zinc deficiency through depletion of accessible body zinc stores developed during the 35-day study.
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PMID:Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women. 92 68

1. The effects of copper and zinc on organ cultures of chick embryo cartilage and bone maintained in low-trace-metal, chemically defined media for up to 8 d were studied macroscopically, histologically and histochemically. Length and wet-weight measurement of explants were assessed statistically. 2. No effects were found with Cu concentrations of 0-5-1-5 mug/ml medium. Between concentrations of 5 and 40 mug Cu/ml medium, lengths and wet-weights of cartilage cultures decreased significantly (P less than 0-001) compared with controls. The decrease was directly proportional to increasing Cu concentration, and that of the length was greater with increasing period of culture (P less than 0-001). 3. With 5--20 mug Cu/ml medium cartilage and bone became yellow in colour, and chondrocytes were swollen, rounded and basophilic. They were detached from their lacunae and the quantity of matrix was reduced. Loss of alkaline phosphatase (EC 3.1.3.1) activity and disappearance of glycogen accompanied the degeneration. Osteogenesis ceased, cells failed to divide and mature, lost their enzymes and died. Cu did not accumulate in the bone matrix. 4. The direct toxic effects of Cu for cartilage and bone may underlie some of the skeletal changes in hepatolenticular degeneration (Wilson's disease). 5. As Zn concentrations were increased from 2-5 to 7-5 mug/ml medium, lengths and wet-weights of cartilaginous cultures were significantly increased (P less than 0-001). As Zn concentrations were further increased (from 10 to 40 mug/ml medium), lengths and wet-weights were significantly decreased (P less than 0-001). 6. Zn stimulated chondrocyte division and vacuolation of cytoplasm. With higher Zn concentrations toxic changes of granular basophilia, lacunar detachment and necrosis were seen. Differentiation and functioning of osteoblasts, osteoclasts and chondroclasts were stimulated by Zn. 7. Zn was found in bone matrix, osteoblasts, osteocytes and hypertrophied chondrocytes.
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PMID:The histological effects of copper and zinc on chick embryo skeletal tissues in organ culture. 95 37

The therapeutic effect of orally administered zinc in 3 patients affected with Acrodermatitis enteropathica is reported. Single daily doses of zinc resulted in rapid improvement of the general condition of these patients and in clinical remission within a week. Serum, urine and hair zinc levels as well as alkaline phosphatase, which were very low before treatment, returned to normal after therapy. This brief report confirms the efficacy of oral zinc in the treatment of Acrodermatitis enteropathica.
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PMID:Treatment of acrodermatitis enteropathica with zinc sulphate. Rerport of 3 cases. 95 34

Certain factors were found to prevent quantitative recovery of soluble alkaline phosphatase from homogenates of chick duodenal mucosa during treatment with n-butanol. Divalent cations such as calcium, manganese and lead interfered when present at 0.1-0.2 mM. Magnesium and zinc were found to reduce enyme recovery when present at 1.0 mM during extraction. These metals had little effect on enzyme activity per se, whether added to the homogenates or enzyme extracts before dilution for assay. However, lead acetate may have a protective or activating effect on phosphatase, at 0.1-10 mM. Other factors affecting the recovery of enzyme activity after butanol solubilization are the state of dilution and pH of the homogenate and individual animal variation.
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PMID:Interference by divalent metals in the preparation of soluble intestinal alkaline phosphatase with n-butanal. 95 79

Liver function tests were carried out for serum zinc turbidity test, icterus index, alkaline phosphatase, bilirubin and transaminases in a series of 222 patients, of whom 119 had prostatic carcinoma, 63 benign hyperplasia of the prostate and 40 congenital abnormality without prostatic trouble. Patients having prostatic carcinoma often displayed abnormally high levels of zinc turbidity test, alkaline phosphatase, bilirubin and transaminases.
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PMID:Liver function in porstatic carcinoma patients. 96 7

Serum zinc concentrations in 234 gravidae showed a gradual fall during the first and second trimesters. From the 25th week of gestation until delivery there is a levelling out of mean zinc values. No correlations between serum zinc, serum HCS, or urinary excretion of oestriol were found. Women with mature infants born by normal delivery showed significantly higher serum zinc during pregnancy than women with abnormal deliveries and/or abnormally developed infants (p less than 0.001). Eight infants showed congenital malformations. Five of the 8 mothers showed the lowest serum zinc concentrations recorded during respective week of pregnancy. A diabetic woman gave birth to an immature infant with multiple skeletal malformations. She showed the lowest serum zinc in the 21st week, and at the same time a very low alkaline phosphatase activity. Her serum proteins and serum HCS were normal. Women with dysmature infants showed significantly lower zinc values during pregnancy (p less than 0.02) than women with mature infants born by normal delivery. Data from studies on zinc metabolism show that there is a requirement of at least 375 mg of zinc during pregnancy in order to meet the demands of normal weight gain. Teenagers, women with multiple pregnancies, women with impaired intestinal absorption due to disease or drugs and in particular women with a low-protein, high-phytate diet seem to risk developing zinc deficiency during pregnancy.
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PMID:Variations in maternal serum zinc during pregnancy and correlation to congenital malformations, dysmaturity, and abnormal parturition. 106 46

Cells of Escherichia coli strain B develop large intracellular vacuoles and exhibit an abnormally long lag phase when inoculated into a defined medium to glucose and salts containing 3 times 10-6 M Cd2+. Early in this lag, about 95% of the cells fail to form colonies when plated on nutrient broth-NaCl-agar. Prior to the initiation of proliferation, the morphology of these cells becomes normal. They regain viability in the absence of deoxyribonucleic acid replication. The rate and extent of growth are normal once proliferation begins. This reversible phenomenon of accommodation to a growth-inhibiting concentration of Cd2+ does not appear to result from a selection of mutant cells. Cells which are proliferating in the presence of Cd2+ accumulate the ion to a very high concentration. In membranes and 31% in the cytoplasm. In unaccommodated cells, the figures are 2%, 75%, and 23%, respectively. The activity of alkaline phosphatase, a zinc-metalloenzyme which is inhibited by cadmum and is located between cell wall and membrane, is not abnormally low in accommodated cells, suggesting that the cadmim is compartmentalized in these cells. Molecular sieve chromatography of cell extracts shows that the Cd2+ is associated with two classes of macromolecules. It appears that accommodation of E. coli to the presence of Cd2+ involves exclusion of the ion from the cell and reversal of damage caused by prior exposure to the ion.
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PMID:Molecular mechanisms of accommodation in Escherichia coli to toxic levels of Cd2+. 109 May 97

The therapeutic effect of orally administered zinc was evaluated in an adult woman with acrodermatitis enteropathica. When she was off therapy and in clinical relapse the plasma zinc concentration (10 mug per 100 ml), serum alkaline phosphatase (3 1U per liter) and urine zinc excretion rate (39 mug per 24 hours) were extremely low. Di-iodohydroxyquin therapy was accompanied by a modest increase in plasma zinc concentrations. Oral zinc sulfate (220 mg three times a day or 50 mg twice a day) resulted in rapid and complete clinical remission, and in a return of plasma zinc, serum alkaline phosphatase and urinary zinc excretion to normal. These data are compatible with a severe zinc deficiency state and indicate that the inherited defect in this disease is either in or closely related to zinc metabolism. The beneficial effects of zinc therapy in this patient provide further confirmation of the efficacy of oral zinc in the treatment of acrodermatitis enteropathica.
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PMID:Zinc therapy of acrodermatitis enteropathica. 109 Aug 26

Alkaline phosphatase of E. coli, isolated by procedures which do not alter its intrinsic metal content, contains 1.3 +/- 0.3 g-atom of magnesium and 4.0 +/- 0.2 g-atom of zinc per molecule of molecular weight 89,000. Magnesium, the role of which has been unappreciated, significantly affects the function and structure of alkaline phosphatase containing either 2 or 4 g-atom of zinc per mole. Magnesium does not activate the apoenzyme but increases the activity of the enzyme containing 2 g-atom of zinc 4.4-fold and that of the enzyme containing 4 g-atom 1.2-fold. The results obtained with enzyme in which cobalt is substituted for zinc are analogous. Moreover, the absorption and electron paramagnetic resonance spectra of cobalt phosphatases reveal the effects of magnesium on cobalt coordination geometry. Addition of magnesium changes the spectral characteristics of the apoenzyme reconstituted with 2 g-atom of cobalt from predominantly octahedral to 4- or 5-coordinate geometry. These two classes of cobalt binding sites have been associated with catalysis and structure stabilization, respectively. Therefore, magnesium controls the occupancy of the catalytic and structural binding sites and modulates the resultant enzymatic activity. Hydrogen-tritium exchange was employed to determine the effects of magnesium on the conformational stability of phosphatase. Magnesium stabilizes the dynamic structural properties, both of apophosphatase and of enzyme containing 2 g-atom of zinc, which is further stabilized by 2 more zinc atoms. The role of magnesium and other metal ions in regulatory processes, only now beginning to be explored fully, will likely emerge as an important avenue for achievement of regulatory effects in metalloenzymes.
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PMID:Role of magnesium in Escherichia coli alkaline phosphatase. 110 31


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