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)

Cholesterol 7 alpha-hydroxylase activity was completely inhibited by incubation with alkaline phosphatase in a reconstituted enzyme system containing a cytochrome P-450, NADPH-cytochrome P-450 reductase and phospholipid. On the other hand, cAMP-dependent protein kinase stimulated cholesterol 7 alpha-hydroxylase activity by 2.5-fold. The modulation of cholesterol 7 alpha-hydroxylase activity was dependent on the amount of phosphatase or kinase added. The phosphatase inhibited enzyme activity was partially reversed by the treatment with protein kinase. These experiments indicate that the reconstituted cholesterol 7 alpha-hydroxylase activity is reversibly regulated by phosphorylation/dephosphorylation mechanism.
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PMID:Modulation of reconstituted cholesterol 7 alpha-hydroxylase by phosphatase and protein kinase. 308 Sep 95

Treatment with alkaline phosphatase of hepatic microsomes prepared from rabbit, rat, and mouse caused a marked decrease of their specific monooxygenase activity (7-ethoxycoumarin-deethylation). This decrease occurred without a significant change in the microsomal content of cytochrome P-450, but with an equally marked decrease of NADPH-cytochrome P-450 reductase (cytochrome c reduction). Thus the phosphatase effect on monooxygenase is mainly due to the inactivation of the reductase.
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PMID:Phosphatase affects microsomal monooxygenase mainly via reductase. 309 91

Incubation of rabbit liver microsomes with alkaline phosphatase resulted in a marked decrease of NADPH-dependent monooxygenase activities. This decrease was found to be correlated with the decrease of NADPH-cytochrome c reductase activity catalyzed by NADPH-cytochrome P-450 reductase. Neither the content of cytochrome P-450, as determined from its CO difference spectrum, nor the peroxide-supported demethylase activity catalyzed by cytochrome P-450 alone was affected by the phosphatase treatment. NADH-cytochrome b5 reductase and cytochrome b5 were not affected by the phosphatase either. NADPH-cytochrome P-450 reductase purified from rabbit liver microsomes lost its NADPH-dependent cytochrome c reductase activity upon incubation with phosphatase in a way similar to that of microsome-bound reductase. Flavin analysis showed that the phosphatase treatment caused a decrease of FMN with concomitant appearance of riboflavin. Alkaline phosphatase, therefore, inactivates the reductase by attacking its FMN, and the inactivation of the reductase, in turn, leads to a decrease of the microsomal monooxygenase activities.
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PMID:The effects of phosphatase on the components of the cytochrome P-450-dependent microsomal monooxygenase. 310 84

The influence of 5,10-dihydroindeno[1,2-b]indole (indenoindole) on carbon tetrachloride (CCl4)-mediated hepatotoxicity and lipid peroxidation were examined. Indenoindole (25 mg/kg body weight) ameliorated the increase in liver enzymes appearing in the plasma 24 hr after CCl4 administration, with about a 63% reduction for alanine transaminase, 56% for ornithine transcarbamylase and 84% for alkaline phosphatase. Indenoindole also partially prevented, in a dose-dependent fashion, the decrease in hepatic cytochromes P-450, total tissue reducing equivalents and hepatic ascorbate levels resulting 4 hr after CCl4 administration. In a homogeneous chemical system consisting of purified soybean phospholipid substrate in chlorobenzene, azobisisobutyronitrile-initiated lipid peroxidation was inhibited by indeno-indole, with 50% inhibition occurring at about 17 microM. Inhibition by indenoindole of iron-ascorbate-initiated lipid peroxidation in aqueous buffer containing phospholipid vesicles was about tenfold more efficient, with 50% inhibition occurring at about 1.5 microM. Presumably, this was due to the increased concentration of indenoindole in the membrane of the phospholipid vesicle. The efficiency of inhibition of lipid peroxidation was in the order of indenoindole = butylated hydroxytoluene (BHT) greater than alpha-tocopherol much greater than indole greater than indene. These 50% inhibition values of lipid peroxidation for these compounds were similar in an assay system composed of NADPH-fortified mouse-liver microsomes initiated with CCl4. For indenoindole, the 50% inhibition value (1.3 microM) was more than two orders of magnitude less than the spectral binding constant for indenoindole to mouse-liver cytochrome P-450 (Kd = 236 microM), implying that the partial inhibition of metabolic activation of CCl4 was not responsible for the inhibition of lipid peroxidation observed with indenoindole in this system. It appears that indenoindole may trap reactive radicals and inhibit lipid peroxidation in vitro. Regardless of whether inhibition is at the level of scavenging CCl4 metabolite radicals, or lipid radicals in membranes, radical trapping provides a plausible mechanism by which this compound inhibited CCl4 hepatotoxicity.
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PMID:Protection against carbon tetrachloride hepatotoxicity by 5,10-dihydroindeno[1,2-b]indole, a potent inhibitor of lipid peroxidation. 316 51

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

A method has been developed for preparing primary monolayer cultures of postnatal rat kidney cortical epithelial cells. These cultures maintained differentiated cell functions and epithelial-like morphology for several days in culture. The presence of alkaline phosphatase and maltase was used to confirm the presence of cells from the renal cortex. The concentrations of these enzymes were maintained in culture until day 3, but had declined significantly by day 5. Similar patterns were observed with cytochrome P-450 and glutathione content, although their concentrations remained stable from day 3 to day 5. Mercuric chloride, cadmium chloride and acetaminophen were evaluated for nephrotoxicity in this culture system. Treatment with these compounds resulted in dose-dependent changes in cell morphology and in biochemical parameters such as lactate dehydrogenase leakage, alkaline phosphatase activity and cellular glutathione content. With this culture system, it was possible to detect the acute toxicities of compounds that produce varying degrees of renal injury. Further development of this kidney culture system may have value in detecting potential nephrotoxins and in studying their mechanisms of toxicity.
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PMID:Development of a primary culture system of rat kidney cortical cells to evaluate the nephrotoxicity of xenobiotics. 353 92

When rats were exposed to 50 ppm NO2 gas for 36 h, remarkable changes in some biochemical levels compared with those of control rats were observed. Namely, levels of total cholesterol, ester cholesterol, total lipids, triglycerides, nitrogen of urea, uric acid, glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and cytochrome P-450 of the exposed rats were decidedly different from those of the control rats. Thus, it was suggested that functions of liver are acutely injured upon exposure to 50 ppm NO2 gas, although extensive pulmonary injury resulting from such an exposure may also be responsible for some of the abnormal serum values.
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PMID:Effects of 50 ppm NO2 gas exposure on physiological functions of rats. 373 29

Maintainance of rats within 3 months on a ration with low content of vitamin E (6 mg/kg as compared with 100 mg/kg in control) did not alter distinctly the enzymatic activity in mitochondria, lysosomes and the activity of the enzymes, metabolizing xenobiotics as well as did not affect the permeability of lysosomal and plasmatic membranes. In subacute T-2 mycotoxicosis of rats kept on control ration the following alterations were noted: decrease in activity of lysosomal enzymes, aniline hydroxylase, carboxyl esterase and in content of cytochrome P-450 in liver tissue simultaneously with two-fold activation of epoxide hydrolase and UDP-glucuronosyl transferase; decrease in non-sedimented activity of lysosomal enzymes; decrease in activity of alkaline phosphatase and of lysosomal enzymes in blood serum. After administration of the toxin into vitamin E deficient rats, its effect was increased, hemorrhagic syndrome was distinctly developed, permeability of lysosomal and plasmatic membranes was increased. Subnormal consumption of vitamin E appears to cause destabilization of biological membranes structure, which is manifested under conditions of stress.
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PMID:[Effect of different supplies of vitamin E on biochemical changes in T-2 mycotoxicosis in rats]. 381 1

Graded hepatic damage was induced in mature lactating dairy cows to measure the sensitivity of several hepatic diagnostic tests. In a preliminary study, cows were dosed with .05, .10 and .20 ml/kg body weight of carbon tetrachloride. Extreme changes occurred in hepatic tests by 24 h post-dosing, and all died by 35 h with massive diffuse centrilobular necrosis of hepatic cord cells. Dosing was decreased to induce non-fatal hepatic changes. Cows in Groups 1, 2, 3 and 4 were orally dosed with .002, .004, .006 or .01 ml/kg body weight of carbon tetrachloride, respectively. Serum enzymes of hepatic origin, bilirubin, plus bromosulfophthalein dye clearance were assayed before dosing and up to d 14 post-dosing. Liver biopsies were performed 24 h post-dosing for histological evaluation and cytochrome P-450 content. Hepatic concentrations of cytochrome P-450 were decreased in all the dosed cows. Serum activities of sorbitol dehydrogenase and gamma-glutamyl transferase were elevated in cows of Groups 3 and 4 and glutamic-oxaloacetic transaminase in cows of Group 4 by 24 h. Serum alkaline phosphatase, glutamic-pyruvate transaminase, lactate dehydrogenase, bilirubin, urobilinogen and bromosulfophthalein dye clearance were not significantly different. Mild to moderate diffuse centrolobular necrosis was observed in livers of cow of Groups 3 and 4, but no pathological changes were seen in Groups 1 and 2.
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PMID:Changes in hepatic function tests to induced toxicity in the bovine liver. 381 83

Compound LY171883 caused dose-related and reversible hepatomegaly in male Fischer 344 rats. Histological examination revealed hepatocellular hypertrophy with no other evidence of liver disease. There were only minor changes in serum glucose, total bilirubin, alkaline phosphatase, and alanine transaminase which were generally unrelated to dose and dissociable from the hepatomegaly. Total liver DNA increased but the DNA concentration decreased, indicating that liver growth involved a combination of hypertrophy and hyperplasia. Total liver protein and RNA increased. Hepatic mitochondrial protein content increased but cytochrome oxidase activity was not changed. There were minor changes in mitochondrial respiratory parameters; however, all the values were in the normal range and there was no indication of mitochondrial toxicity. Microsomal protein, drug-metabolizing activity, and cytochrome P-450 increased, but glucose-6-phosphatase activity was not changed. The induction of drug-metabolizing enzymes and absence of toxicity were evidence that the hepatomegaly was an adaptation to an increased functional load in the liver. An increase in catalase activity suggested that the response may have also involved peroxisomes. In addition to rats, LY171883 administration caused hepatomegaly in mice and hamsters at daily exposures exceeding 100 mg/kg. The response was not observed in guinea pigs, beagle dogs, or rhesus monkeys given maximum tolerated doses, indicating LY171883-induced hepatomegaly is not a response common to all species. The doses required to elicit hepatomegaly greatly exceeded doses that produce pharmacological efficacy in animals and those that are expected to be used clinically. Since humans will not receive doses comparable to those given rodents, and considering that the primate species tested did not experience hepatomegaly, it is unlikely that the effect observed in rodents can be extrapolated to humans.
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PMID:Characterization of liver enlargement induced by compound LY171883 in rats. 384 Jan 8


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