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)

Liver transplantation is the only effective treatment for hereditary tyrosinaemia type I (McKusick 276700). We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43 mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The almost complete inhibition of porphobilinogen synthase in erythrocytes was abolished and the excretion of 5-aminolevulinate decreased to within or slightly above the reference range. The concentration of alpha-fetoprotein decreased in four patients to 1.3-7.5% of initially high values over 6-8 months. Improved liver function was reflected by normal concentrations of prothrombin complex and in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in serum. Computed tomography revealed regression of hepatic abnormalities in three patients. One patient developed rickets 6 months before treatment and had excreted high concentrations of markers of tubular dysfunction--after 3 weeks of treatment, this excretion had disappeared. No side-effects were encountered. Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation of porphyrin synthesis will eliminate the risk of porphyric crises. This type of treatment may thus offer an alternative to liver transplantation in hereditary tyrosinaemia.
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PMID:Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. 135 48

One-day old American kestrel (Falco sparverius) nestlings were orally dosed daily with 5 microliters/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.
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PMID:Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius). 286 Oct 31

Previous studies have suggested an association of zinc deficiency and short stature in some children and adults with sickle cell disease (SCD). As a result, zinc supplementation has been recommended for these patients. The mechanism for zinc deficiency in certain patients with SCD is unknown, although renal loss of zinc has been suggested as a contributing factor. The zinc status of 29 subjects with SCD and 18 black controls was studied. No evidence of zinc deficiency in our population with SCD was found when plasma and cellular zinc levels were measured. Likewise, levels of two zinc-dependent enzymes, alkaline phosphatase and delta-aminolevulinic acid dehydratase, were normal in these subjects with SCD. Although adolescent subjects with SCD tended to be shorter than control subjects, there was no correlation between the height-forage z score and plasma zinc levels (r = -.31). It was concluded that zinc deficiency was not present in our population with SCD, and that there was no correlation between plasma zinc levels and the height-for-age z score in growing adolescent patients with SCD. These findings suggested that zinc supplementation may not be necessary in all patients with SCD.
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PMID:Zinc status in children and young adults with sickle cell disease. 319 34

The influence of chelating agents (1 mmol/kg/day X 6,i.p.) on trace metal mobilization and activities of certain metalloenzymes was investigated in rats. Calcium disodium ethylenediamine tetraacetate (CaNa2EDTA) and calcium trisodium diethylenetriamine pentaacetate (CaNa3DTPA) enhanced urinary excretion of Zn, while sodium 2,3-dimercaptopropane-1-sulfonate (NaDMPS) and sodium diethyldithiocarbamate (NaDDC) increased that of Cu. The activity of Zn-metalloenzymes-blood delta-aminolevulinic acid dehydratase (delta-ALA-D), plasma alkaline phosphatase (ALP) and that of Cu-metalloenzyme-plasma amine oxidase was decreased as a consequence of chelation therapy. However, hepatic levels of delta-ALA-D, ALP and alcohol dehydrogenase remained unaffected by chelation. The activity of hepatic Fe-metalloenzyme-catalase was increased by polyaminocarboxylic acids and lowered by thiol chelators. The metal chelators decreased the hepatic glutathione levels.
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PMID:Influence of metal chelators on metalloenzymes. 361 94

The synthesis of various cell components was examined during the anaerobic photosynthetic growth of synchronous populations of Rhodopseudomonas spheroides. Net deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein increased continuously as did the rate of incorporation of radioactive precursors into protein. The rates of incorporation of radioactive precursors into RNA and DNA were marked by abrupt discontinuities. It is not clear whether these discontinuities represent changes in rates of synthesis or fluctuations in precursor pools. Although the synthesis of bacteriochlorophyll occurred in a continuous manner, those enzymes examined which are involved in the synthesis of tetrapyrroles, i.e., succinyl CoA thiokinase, delta-aminolevulinic acid synthetase, and delta-aminolevulinic acid dehydrase, increased discontinuously. Two other enzymes not involved in tetrapyrrole biosynthesis were examined. Alkaline phosphatase increased in a stepwise manner during the division cycle, whereas the synthesis of ornithine transcarbamylase increased rapidly before leveling off for a period of time until synthesis began again. In each instance of discontinuous enzyme synthesis, increases occurred at regular and characteristic times during the division cycle. Ammonium sulfate precipitation was employed to remove low molecular weight end product inhibitors from enzyme preparations. These studies suggested that the stepwise increases in enzyme activity observed in the present investigation were not affected by periodic end product inhibition. A temporal map of enzyme synthesis during the division cycle was constructed. Both delta-aminolevulinic acid synthetase and delta-aminolevulinic acid dehydrase appeared early in the division cycle, whereas alkaline phosphatase and succinyl CoA thiokinase appeared later on.
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PMID:Enzyme and nucleic acid formation during synchronous growth of Rhodopseudomonas spheroides. 565 Aug 92

Two main equal groups of clinically healthy, non pregnant rabbits were classified into 4 subgroups (5 rabbits each). The 1st and 2nd subgroups were treated with sulphaquinoxaline or sulphadiazine in a single oral dose of 100 mg/kg b. wt., while the 3rd and 4th subgroups received a repeated oral dose of 100 mg/kg b. wt., daily for 5 successive days, respectively. The second main group received lead acetate in a dose of 4.2 mg/kg b. wt. per day for 2 months, then was classified as in case of the 1st main group and administered the respective sulphonamides in their recommended doses. The experimental lead intoxication was found to decrease the free delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in blood of lead intoxicated rabbits after 4 and 8 weeks. Also, the ratio of free and with glutathione reactivated delta-ALA-D was increased 2.9 and 2.2 after 4 and 8 weeks, respectively as compared with before lead administration (1.19), indicating toxicity. The sulphonamide/creatinine ratio was increased after administration of both sulphonamides but higher in lead intoxicated rabbits as compared with healthy ones. The AST/ALT ratio was decreased 4 and 8 weeks after lead exposure. The AST, ALT and AST/ALT ratio, alkaline phosphatase, urea and creatinine were not altered in healthy rabbits. Repeated oral administration of sulphadiazine caused a significant increase in serum AST, ALT, alkaline phosphatase and creatinine level in healthy and lead intoxicated rabbits. On the other hand, AST/ALT ratio in both healthy and lead intoxicated rabbits was found to decrease 1 h after the last dose as compared with before treatment.
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PMID:Interaction between lead toxicity and some sulphonamides in rabbits: effect on certain blood constituents and serum enzymes. 801 95

The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.
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PMID:Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice. 955 1

Male albino rats were given a single oral dose of gallium arsenide (GaAs) (100, 200 or 500 mg/kg). Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was inhibited in all the three GaAs-exposed groups accompanied by elevated urinary excretion of ALA. A significant increase in serum aspartate aminotransferase (AST) activity, and gamma-glutamyltranspeptidase (gamma-GT) was observed. A significant increase in hepatic malondialdehyde (MDA) and a decrease in hepatic glutathione contents were also noted. Renal alkaline phosphatase activity, urinary ALA and protein excretion increased significantly on GaAs exposure. These changes were accompanied by significant alterations in almost all the immunological variables, with an increase in gallium and arsenic concentration in blood and soft tissues. While most of the above biochemical alterations were prominent at day 7 following single exposure to 200 and 500 mg/kg GaAs, most of the immunological indices altered with all the three doses and remained high even at day 21. The results suggest only a moderate effect of GaAs on renal and hepatic tissues. By contrast, immunological and haematological systems are the most vulnerable to the toxic effects of GaAs.
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PMID:Acute oral gallium arsenide exposure and changes in certain hematological, hepatic, renal and immunological indices at different time intervals in male Wistar rats. 957 7

Thirty-five (five groups with seven animals each) male albino rats (initial average weight = 44 g) were fed phytate-rich diets (analysed phytic acid concentration = 6.9 g/kg) based on maize and soy bean meal (5 g Ca, 3 g P, 1.2 g Mg, 23 mg Zn, 10 mg Pb, 5 mg Cd/kg diet). Experimental diets were supplemented with 0, 2, 4, 6 and 8 g calcium from CaCO3 per kg. The supplementation of increasing amounts of calcium resulted in a dose-dependent decrease in the apparent absorption of phosphorus. Furthermore, apparent zinc absorption and femur zinc concentration were moderately decreased due to the calcium supplementation. Kidney Cd concentration was significantly lower in rats that were fed the high calcium diets in comparison with the control animals. Femur lead concentration and hepatic delta-aminolevulinic acid dehydratase, which are known to be sensitive parameters of lead accumulation remained unchanged by the different dietary treatments. Magnesium absorption as well as liver and plasma zinc concentration and activity of plasma alkaline phosphatase were also unaffected. Although calcium supplementation may lead to a decrease in the accumulation of certain heavy metals such as cadmium, the carry-over of lead was not affected under the given experimental conditions. Furthermore, calcium-phytate-zinc interactions may adversely affect zinc bioavailability in growing rats.
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PMID:Effect of calcium supplements to a maize-soya diet on the bioavailability of minerals and trace elements and the accumulation of heavy metals in growing rats. 1100 45

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelator, is gaining recognition recently as a better chelator than meso 2,3-dimercaptosuccinic acid (DMSA) in decreasing heavy metal burden in tissues because of its lipophilic character. There is, however, little information available on the toxicological properties of this chelator after repeated administration in animals. In the present study, we investigated the dose-dependent effect of MiADMSA on various biochemical parameters suggestive of alterations in haem biosynthesis and hepatic, renal and brain oxidative stress after 21 days of repeated intraperitoneal (i.p.) or oral (p.o.) administration to rats. The concentration of essential metals in blood and soft tissues was determined along with histopathological observations of hepatic and renal tissues. The results suggest that MiADMSA administration had no effect on blood delta-aminolevulinic acid dehydratase activity. However, an increase in zinc protoporphyrin and a decrease in haemoglobin levels were noted in animals given MiADMSA i.p. A moderate increase in serum alkaline phosphatase suggested mild hepatotoxicity at the highest dose (100 mg kg(-1), i.p.). This was confirmed by histopathological examinations, which identified basophilic stippling, granulation of the cytoplasm, haemorrhage and congestion. At the highest dose, levels of hepatic thiobarbituric acid reactive substance and oxidized glutathione were increased above those of control values. Levels of hepatic reduced glutathione were decreased. Taken together, these observations point to oxidative stress. In animals administered MiADMSA i.p. there was an increase in the brain malondialdehyde levels at the two higher doses (50 and 100 mg kg(-1)). Essential metal status revealed a significant effect of MiADMSA (p.o.) in increasing blood zinc while significantly decreasing the kidney zinc level. The most significant adverse effect of MiADMSA was on copper concentration, which showed significant depletion from almost all major organs. Magnesium levels in blood decreased but increased in liver of MiADMSA-administered rats. Histopathological observations of liver and kidneys suggest few moderate lesions. It can be concluded that repeated administration of MiADMSA is compromised with some mild toxic effect, particularly the loss of copper. The effects during oral administration are comparatively less pronounced than by the i.p. route.
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PMID:Haematological, hepatic and renal alterations after repeated oral or intraperitoneal administration of monoisoamyl DMSA. I. Changes in male rats. 1242 40


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