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)

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet for up to 59 weeks. Liver sections were histochemically analyzed for the following parameters: basophilia, glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The stop experiments revealed that many of the oval cells proliferating during the first 4-6 weeks may undergo necrotic changes and disappear with time, whereas cholangiofibroses appearing in animals fed CDE for at least 10 weeks are persistent lesions. The sequence of lesions seen in this study, leading from persistent oval cells through cholangiofibroses to cholangiofibromas, strongly suggests that the oval cells are the precursor cells of cholangiocellular tumors. The proliferating oval cells and the hepatic foci consisting of clear and acidophilic or mixed cell populations were always spatially separated and no transitions between oval and parenchymal cells were observed. These results argue against a precursor-product relationship between oval and parenchymal cells. Both proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, SYN and G6PASE activities were also detected in these lesions. Persistent glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as decreased G6PASE activity. These results indicate that the characteristic metabolic pattern of preneoplastic hepatic foci is independent of the further administration of the carcinogenic diet. The shift from glycogen metabolism to glycolysis and the pentose phosphate pathway occurring during the later stages of CDE-induced hepatocarcinogenesis is an autogenous process apparently directing the disturbed carbohydrate metabolism towards alternative metabolic pathways. A similar metabolic shift also seems to take place during cholangiocarcinogenesis.
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PMID:Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet. 131 Sep 7

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

In continuation of earlier studies on murine neoplastic liver lesions, we characterized by histochemical methods the phenotype of hepatocellular adenomas and carcinomas induced by single injections of diethylnitrosamine (1.25, 2.5, or 5.0 micrograms/g of body weight) in 15-day-old C57BL/6 x male C3H F1 mice. The hepatocellular adenomas were composed predominantly of basophilic cells but stored excessive amounts of fat and glycogen in large portions of the tumors. Irrespective of the carcinogenic dose, the adenomas showed a consistent histochemical pattern. Glycogen synthase and phosphorylase were highly active in the hepatocytes that stored glycogen. In cells poor in, or free of, this polysaccharide, these enzymes were only moderately active or even inactive. In glycogen-storing parts of the adenomas, the activity of adenylate cyclase was reduced compared with normal liver parenchyma, but in fat-storing portions it was elevated. In a few adenomas, uniform increase in adenylate cyclase activity could be encountered. The levels of ATPase, acid phosphatase, and glucose-6-phosphatase were either increased or decreased. Glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase showed an increased activity in all adenomas compared with preneoplastic foci, which in turn exhibited a higher glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activity than the surrounding parenchyma or the liver of untreated controls. The hepatocellular carcinomas showed remarkable histochemical changes compared with adenomas. The levels of fat and glycogen and the activities of glycogen synthase, phosphorylase, and in most cases also that of glucose-6-phosphate dehydrogenase, were reduced significantly. In contrast, adenylate cyclase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase, and also alkaline phosphatase showed a striking elevation in developing carcinomas. Similar, although more pronounced, histochemical changes were seen in the advanced hepatocellular carcinomas. These observations indicated that progression from adenomas to hepatocellular carcinomas was associated with a change in the activity of several enzymes involved in cell membrane function, glycogen metabolism, the oxidative pentose phosphate pathway, and glycolysis.
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PMID:Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine. 184 80

Previous studies have shown that phosphorylase phosphatase can be isolated from rabbit liver and bovine heart as a form of Mr approximately 35,000 after an ethanol treatment of tissue extracts. This enzyme form was designated as protein phosphatase C. In the present study, reproducible methods for the isolation of two forms of protein phosphatase C from rabbit skeletal muscle to apparent homogeneity are described. Protein phosphatase C-I was obtained in yields of up to 20%, with specific activities toward phosphorylase a of 8,000-16,000 units/mg of protein. This enzyme represents the major phosphorylase phosphatase activity present in the ethanol-treated muscle extracts. The second enzyme, protein phosphatase C-II, had a much lower specific activity toward phosphorylase a (250-900 units/mg). Phosphatase C-I and phosphatase C-II had Mr = 32,000 and 33,500, respectively, as determined by sodium dodecyl sulfate disc gel electrophoresis. The two enzymes displayed distinct enzymatic properties. Phosphatase C-II was associated with a more active alkaline phosphatase activity toward p-nitrophenyl phosphate than was phosphatase C-I. Phosphatase C-II activities were activated by Mn2+, whereas phosphatase C-I was inhibited. Phosphatase C-I was inhibited by rabbit skeletal muscle inhibitor 2 while phosphatase C-II was not inhibited. Both enzymes dephosphorylated glycogen synthase and phosphorylase kinase, but displayed different specificities toward the alpha- and beta-subunit phosphates of phosphorylase kinase (Ganapathi, M. K., Silberman, S. R., Paris, H., and Lee, E. Y. C. (1980) J. Biol. Chem. 246, 3213-3217). The amino acid compositions of the two proteins were similar. Peptide mapping of the two proteins showed that they are distinct proteins and do not have a precursor-proteolytic product relationship.
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PMID:Isolation and characterization of rabbit skeletal muscle protein phosphatases C-I and C-II. 632 85

Regulation of the dephosphorylation of glycogen synthase in extracts from rat heart has been studied by adding exogenous phosphatase to the extract. These experiments were possible only because the endogenous protein phosphatase activity of the extract could be inhibited by KF under conditions where alkaline phosphatase activity was not. The concentration of substrate (glycogen synthase from the heart extract) and catalyst (purified E. coli alkaline phosphatase) could be varied independently, by adding known amounts of alkaline phosphatase to the KF-containing heart extracts. Alkaline phosphatase could completely dephosphorylate glycogen synthase while phosphorylase was unchanged. The rate of dephosphorylation was proportional to both the concentration of alkaline phosphatase added to the tissue extract and the amount of glycogen synthase in the extract. The Km for glycogen synthase was close to the concentration found in heart tissue. The Km and the maximum rate of dephosphorylation were both dependent on the phosphorylation state of the glycogen synthase. Less phosphorylated enzyme forms were dephosphorylated faster. These results indicate the necessity for precise control of many variables in studying the rate of glycogen synthase dephosphorylation. Alkaline phosphatase-catalyzed dephosphorylation could be inhibited by physiological concentrations of glycogen. Glycogen synthase dephosphorylation in extracts from fasted-refed rats was less sensitive to glycogen inhibition than in extracts from normal animals. The phosphorylation state of the glycogen synthase in these animals was assessed by kinetic studies to show that differences in phosphorylation state probably could not account for the observations. Fasting led to a decreased rate of dephosphorylation of glycogen synthase due to both an apparent change in kinetic properties of glycogen synthase as a substrate for alkaline phosphatase, and an increased inhibitory effect of glycogen. Stable modifications of glycogen synthase caused by altered nutritional states in the animals are thought to produce these effects.
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PMID:Dephosphorylation of glycogen synthase in rat heart extracts by E. coli alkaline phosphatase. Use of an exogenous phosphatase to study substrate-mediated regulation of dephosphorylation. 681 91

Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen content, basophilia, and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and gamma-glutamyltranspeptidase (GGT). RCTs displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with the normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK, LDH) and the pentose phosphate pathway (G6PDH), while negative G6Pase and low SDH activity were observed in these cells. The majority of RCTs showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCTs. Markedly enlarged cells with atypical nuclei were detected in some advanced RCTs. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in these enlarged cells than in other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in RCTs in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early during carcinogenesis, but additional studies on early stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:Enzymic pattern of preneoplastic and neoplastic lesions induced in the kidney of CBA mice by 1,2-dimethylhydrazine. 781 30

As previously shown for rabbit liver glycogen, rabbit muscle glycogen contains a small amount of phosphate ester and there is an intermolecular heterogeneity in phosphate content such that the glycogen may be fractionated on DEAE-cellulose into components differing 10-fold in their phosphate contents. We now know that the phosphate ester is of two types, mono and di. The availability of the phosphomonoester component to hydrolysis by alkaline phosphatase is sterically regulated and is highest in the fraction of highest total phosphate content. The ability of the glycogen fractions to act as primers for glycogen synthase also varies with phosphate content, differing overall by > 2-fold. The priming ability increases with increasing phosphate content. We suggest that the phosphate content of a glycogen molecule may be related to its age and that this may be used as a metabolic marker when studying the turnover of glycogen, also that phosphate may be a signal for transport of glycogen to the lysosome. The phosphodiester grouping may act as a point of branching in glycogen, additional to the recognized interglucosidic branch, and is a candidate for the acid- and alkali-labile bond that has been reported in glycogen.
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PMID:The role of phosphate in muscle glycogen. 791 62

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25 micromol/L. In the nontransformed osteoblasts, some vanadyl-saccharide complexes stimulated the mitogenesis (115% basal) in the same range of concentration. The glucose and sucrose complexes were the most efficient inhibitory agents (65% and 88% of inhibition vs. basal, respectively) for tumoral cells at 100 micromol/L. The galactose and turanose complexes exerted a similar effect in the nontransformed osteoblasts. On the other hand, all the complexes promoted the phosphorylation of the extracellular regulated kinases (ERKs). All together, these results indicate that the stimulation of ERKs is not the only factor that plays a role in the proliferative effects of vanadium derivatives since some compounds were inhibitory proliferating agents. Cell differentiation was evaluated by alkaline phosphatase specific activity and collagen synthesis in UMR106 cells. All the complexes inhibited alkaline phosphatase activity, with galactose complex as the most effective compound (IC50 = 43 micromol/L). The complex with the trehalose TreVO was the most effective agent to stimulate collagen synthesis (142% basal) and glucose consumption (132% basal). A cytosolic tyrosine protein kinase and the kinase-3 of glycogen synthase seem to be involved in the stimulation of glucose consumption by vanadium derivatives. In this series, only TreVO gathered the characteristics of a good insulin mimetic and osteogenic drug. In addition, this complex was a good promoting agent of nontransformed osteoblast proliferation, whereas it inhibited tumoral osteoblasts. GluVO, the complex with glucose, was also more toxic for tumoral than for nontransformed cells. These 2 vanadium derivatives are good potential antitumoral drugs. All the results suggest that the biological effects of vanadium compounds are a complex phenomenon influenced by the complexation, the dose, and the nature of the ligands and the cells.
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PMID:Vanadyl(IV) complexes with saccharides. Bioactivity in osteoblast-like cells in culture. 1699 40

Seasonal changes in physiology of vertebrate animals are triggered by environmental cues including temperature, day-length and oxygen availability. Crucian carp (Carassius carassius) tolerate prolonged anoxia in winter by using several physiological adaptations that are seasonally activated. This study examines which environmental cues are required to trigger physiological adjustments for winter dormancy in crucian carp. To this end, crucian carp were exposed to changing environmental factors under laboratory conditions: effects of declining water temperature, shortening day-length and reduced oxygen availability, separately and in different combinations, were examined on glycogen content and enzyme activities involved in feeding (alkaline phosphatase, AP) and glycogen metabolism (glycogen synthase, GyS; glycogen phosphorylase, GP). Lowering temperature induced a fall in activity of AP and a rise in glycogen content and rate of glycogen synthesis. Relative mass of the liver, and glycogen concentration of liver, muscle and brain increased with lowering temperature. Similarly activity of GyS in muscle and expression of GyS transcripts in brain were up-regulated by lowering temperature. Shortened day-length and oxygen availability had practically no effects on measured variables. We conclude that lowering temperature is the main trigger in preparation for winter anoxia in crucian carp.
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PMID:Lowering Temperature is the Trigger for Glycogen Build-Up and Winter Fasting in Crucian Carp (Carassius carassius). 2685 73


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