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)

The following procedures have been used to prepare fifteen modified dinucleoside monophosphates: (a) bisulfite-catalyzed transamination with aniline to give an N4-phenylcytidine (CPh), (b) bisulfite-catalyzed transamination with beta-naphthylamine to give an N4-beta-naphthylcytidine (CbetaN), (c) alkylation with 7-bromomethylbenz[a] anthracene to afford a 7(benz[a]anthryl-7-methyl)guanosine (GMBA), and (d) reaction with N-acetoxy-2-acetylaminofluorene to give an 8-(N-2-fluorenylacetamido)guanosine (GAAF). The compounds prepared were A-CPh, CPh-A, CPh-G, U-CPh, CPh-U, A-CbetaN, CbetaN-A, G-CbetaN, CbetaN-G, U-CbetaN, CbetaN-U, GMBA-U, U-GMBA, GAAF-U, and U-GAAF. All of the modified compounds were hydrolyzed to the expected monomers with venom and spleen exonucleases. Hydrolysis by micrococcal nuclease was inhibited in the following cases: A-CPh, A-CbetaN, U-GMBA, and U-GAAF. The first three reactions above were applied to denatured calf thymus DNA to prepare modified DNA samples containing from 0.3 to 2.0% bound aromatic residues. The modified nucleic acids were completely hydrolyzed to nucleosides by the combination of venom exonuclease, deoxyribonuclease I and alkaline phosphatase. The same results were obtained with a combination of spleen exonuclease, deoxyribonuclease II, and alkaline phosphatase. Hydrolysis of the modified nucleic acids by micrococcal nuclease and alkaline phosphatase afforded primarily nucleosides, with some dinucleoside monophosphates. The amount of the latter did not exceed that found in the hydrolysis of control DNA, however. Other workers have observed inhibition of enzymatic hydrolysis of nucleic acids modified by aromatic carcinogens. We postulated that their results may have been caused by cross-links, which were avoided in our studies.
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PMID:Preparation and enzymatic hydrolysis of dinucleoside monophosphates and DNA modified with aromatic residues. 55 43

Effects of antitumor agents on rat liver microsomal drug-metabolizing enzyme activities and thymus lymphocytes were studied in male Wistar rats. High doses of 5-fluorouracil (5-FU) and cyclophosphamide (CP) given parenterally for 6 days caused a partial decrease in whole body weight and the microsomal enzyme content such as cytochrome P-450 and cytochrome b5. Aniline p-hydroxylase and aminopyrine N-demethylase activities also decreased in rats dosed for 5 days decreased compared with the control. Both compounds in the high concentrations produced spectral change of "modified type II". However, the magnitude of the spectral changes observed was independent of the the concentration of substrate added. The addition of NADPH to the microsomes-substrate mixture modified the spectral change. Both drugs caused a considerable decrease in thymus weight and the number of thymus lymphocytes, while the alkaline phosphatase activity was enhanced in 5-FU groups, indicating that the agents cause a significant involution of the thymus. Decrease in the total number of the lymphocytes was greater than that in the blood leucocytes.
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PMID:Antitumor agents. I. Effect of 5-fluorouracil and cyclophosphamide on liver microsomes and thymus of rat. 100 1

To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl4-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl4-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl4 administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl4-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cli) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cli may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl4 as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis-Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude that in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.
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PMID:Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis. 205 6

This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt.
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PMID:Subchronic oral toxicity of triethyl lead in the male weanling rat. Clinical, biochemical, hematological, and histopathological effects. 225 21

The enzyme activities, which are influenced by the vitamin C level in tissues, were measured to evaluate the vitamin C activity of erythorbic acid (ErA) in guinea pigs administered ErA. Guinea pigs were divided into two groups: animals in one group (control group) were administered 1, 5, and 100 mg/day ascorbic acid (AsA) and those in the other group (supplemented group) were administered 1, 5, 20, and 100 mg/day ErA for 16 days. At the end of the experimental period, they were sacrificed, blood was collected, and their livers were removed. The activities of liver aniline hydroxylase, of liver acid phosphatase, and of serum alkaline phosphatase, and the content of liver cytochrome P-450 were assayed. The activities of aniline hydroxylase and serum alkaline phosphatase and the content of liver cytochrome P-450 of the guinea pigs administered 1 mg ErA were lower than those of the guinea pigs administered 1 mg AsA. However, the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered 5 mg or more of ErA were similar in level to those in the guinea pigs administered 5 mg AsA. These results suggested that administration of a considerably high amount of ErA to guinea pigs showed a similar vitamin C activity to that of AsA, which might suggest that vitamin C activity of ErA may be more than one-twentieth that of AsA, as has been generally believed.
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PMID:Net vitamin C activity of erythorbic acid in guinea pigs. 229 26

Mercuric chloride was administered once i.p. to female Fischer-344 rats at doses of 0, 0.2, 0.6 and 1.8 mg/kg. Although there were no alterations in the urinary excretion of lactate dehydrogenase, significant elevations in the activities of urinary (U) alkaline phosphatase, glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) indicated that mercuric chloride was nephrotoxic. There was no evidence of hepatotoxicity as hepatic glucose-6-phosphatase and serum sorbitol dehydrogenase were essentially unaffected by mercuric chloride administration. The activities of ethylmorphine demethylase, hexobarbital oxidase and aldrin epoxidase determined in vitro were not inhibited by mercuric chloride although aniline hydroxylase activity was decreased. Of the four phase-II reactions measured, only the glucuronidation of chloramphenicol was diminished by treatment with mercuric chloride. Results from the in vivo studies on the metabolism of lindane, which indicated no change in the excretion of free or conjugated metabolites, were in close agreement with the in vitro data suggesting that the nephrotoxic effects of mercuric chloride do not alter the urinary excretion of the model substrate lindane.
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PMID:A comparison of in vitro and in vivo methods for evaluating alterations in hepatic drug metabolism following mercuric chloride administration. 242 44

Changes in hepatic microsomal mixed-function oxidase enzyme levels (aniline hydroxylase, aminopyrine demethylase, glutathione S-transferase), glutathione content, total sulphydryl content, and plasma enzyme levels of aspartate transaminase, alanine transaminase and alkaline phosphatase were studied in male Swiss albino mice exposed to Salmonella typhimurium endotoxin (50-150 micrograms per mouse, LC50 141.82 micrograms). Animals exposed to the same dose of endotoxin but pretreated with protein A of Staphylococcus aureus (5 micrograms/per mouse) protected the animals from both mortality and depletion of biotransformation enzymes.
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PMID:Protein A protects mice from depletion of biotransformation enzymes and mortality induced by Salmonella typhimurium endotoxin. 268 31

The effect of erythorbic acid (ErA) administration on activities of liver aniline hydroxylase, liver acid phosphatase, and serum alkaline phosphatase, and the content of liver cytochrome P-450 was studied to determine whether or not ErA would affect the availability of ascorbic acid (AsA) in normal and AsA-deficient guinea pigs. In experiment I, changes of the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered AsA and/or ErA and sacrificed on days 4, 10, 16, and 30 were examined. Moreover, in experiment II, after 16 days of depletion of AsA, the guinea pigs were administered AsA and/or ErA. These animals were sacrificed on days 0, 4, and 20 of the repletion period, after which the activities of drug metabolic enzyme and phosphatases and content of cytochrome P-450 during recovery were observed. The enzyme activities and cytochrome P-450 content of AsA-supplemented guinea pigs were similar to those of ErA-supplemented animals and also similar to those of both AsA and ErA-supplemented guinea pigs throughout the experimental period. During the repletion of the AsA-depleted guinea pigs, there were no significant differences in these enzyme activities and cytochrome P-450 content among the animals administered AsA and/or ErA. These results suggested that ErA administration may not affect the AsA availability in the guinea pigs.
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PMID:Effect of erythorbic acid administration on activities of drug metabolic enzyme and phosphatases in guinea pigs administered an adequate amount of ascorbic acid. 273 6

Alterations in microsomal drug metabolizing enzymes, microsomal lipids and some serum enzymes following pre-treatment of rats with therapeutic doses of four structurally different antimalarial compounds, chloroquine (CQ), quinine (Q), quinacrine (QK) and primaquine (PQ) have been investigated. CQ and Q significantly decreased the activities of aminopyrene N-demethylase, aniline hydroxylase and both microsomal and cytosolic glutathione S-transferases. Only aniline hydroxylase was markedly decreased by QK, while PQ did not have much effect on any of these enzymes. CQ, Q and QK significantly increased the cholesterol:phospholipid ratio while all four compounds decreased the phosphatidyl choline:sphingomyelin (PC/S) ratio. All the drugs increased the activities of the serum enzymes glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and alkaline phosphatase. The possible relationships of these results to structural variations in the four drugs being investigated has been discussed.
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PMID:Drug induced alterations in some rat hepatic microsomal components: a comparative study of four structurally different antimalarials. 286 Oct 39

The enzyme activities which depended on the ascorbic acid (AsA) tissue levels were assayed to investigate the effect of erythorbic acid (ErA) administration on the AsA availability in the guinea pigs administered 5 mg of AsA/day or 1 mg of AsA/day. The guinea pigs were given 5 mg of AsA and 1, 5, 20, 100 mg of ErA/day, or 1 mg of AsA and 1 or 20 mg of ErA/day for 16 days. The animals were sacrificed, blood was collected, and their livers were removed. The activities of liver aniline hydroxylase, liver acid phosphatase, and serum alkaline phosphatase, as well as the liver cytochrome P-450 content were measured. These enzyme activities and the liver cytochrome P-450 content of animals administered 5 mg of AsA seemed to show no change regardless of ErA supplement. Animals administered 1 mg of AsA showed different activities of liver aniline hydroxylase and liver acid phosphatase compared with those of animals administered 5 mg of AsA; however, the enzyme activities in animals administered 20 mg of ErA together with 1 mg of AsA were similar to those of the animals administered only 5 mg of AsA. These results indicated that ErA administration had no effect on the enzyme activities and the liver cytochrome P-450 content in the 5 mg AsA-supplemented animals, but administration of 20 mg of ErA was effective to maintain at normal levels the activities of liver aniline hydroxylase and liver acid phosphatase in the 1 mg AsA-supplemented animals.
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PMID:Effect of graded doses of erythorbic acid on activities of drug metabolic enzyme and phosphatases in guinea pigs. 323 Apr 15


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