Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of D-valine medium to inhibit fibroblasts in cultures derived from kidneys of various mammals has enabled the selective proliferation of epithlial cells in the absence of fibroblast overgrowth. Studies of these selected epithelial cells have demonstrated the presence of D-amino acid oxidase, carbonic anhydrase, high levels of alkaline phosphatase and the renal specific pattern of lactate dehydrogenase. The presence of these renal enzymes suggests that the selected epithelial cells are of renal tubular origin and indicates that these differentiated functions are retained in cultured cells.
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PMID:Renal enzymes in kidney cells selected by D-valine medium. 1 81

A 1-mg/ml amount of threonine (8.4 mM) inhibited growth and sporulation of Bacillus subtilis 168. Inhibition of sporulation was efficiently reversed by valine and less efficiently by pyruvate, arginine, glutamine, and isoleucine. Inhibition of vegetative growth was reversed by asparate and glutamate as well as by valine, arginine, or glutamine. Cells in minimal growth medium were inhibited only transiently by very high concentrations of threonine, whereas inhibition of sporulation was permanent. Addition of threonine prevented the normal increase in alkaline phosphatase and reduced the production of extracellular protease by about 50%, suggesting that threonine blocked the sporulation process relatively early. 2-Ketobutyrate was able to mimic the effect of threonine on sporulation. Sporulation in a strain selected for resistance to azaleucine was partially resistant. Seventy-five percent of the mutants selected for the ability to grow vegetatively in the presence of high threonine concentrations were found to be simultaneously isoleucine auxotrophs. In at least one of these mutants, the threonine resistance phenotpye could not be dissociated from the isoleucine requirement by transformation. This mutation was closely linked to a known ilvA mutation (recombination index, 0.16). This strain also had reduced intracellular threonine deaminase activity. These results suggest that threonine inhibits B. subtilis by causing valine starvation.
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PMID:Inhibition of Bacillus subtilis growth and sporulation by threonine. 10 59

1. Intestinal brush border enzymes have heterogeneous rates of turnover, the largest proteins having the fastest turnover. Since the membrane faces the intestinal lumen, the effects of pancreatic factors were examined in mediating this turnover. Surgical subtotal pancreatectomy was used as an experimental model to study the turnover of brush border proteins in the absence of most pancreatic secretions. 2. Subtotal (95%) pancreatectomy of rats was found to cause elevations by about 50% of total activity and specific activities of certain brush border enzymes (maltase, sucrase, lactase), but not of others (alkaline phosphatase, trehalase). Rats were judged to be functionally deficient in pancreatic proteolytic enzymes (a) by demonstration of vitamin B-12 malabsorption, which was corrected by trypsin, and (b) by the finding of only about 20% of proteolytic activity appearing in the lumen after a test meal when compared to control. 3. To measure protein turnover in vivo the method of double labelling was used, where [3H]- and [14C]valine were administered intraduodenally in sequence 10 h apart. With this technique, a high 3H/14C ratio is correlated with rapid turnover. Proteins with apparent molecular weights of about 200 000-270 000 were found to turn over more rapidly than smaller proteins. 3H/14C ranged from 4.7 to 6.2 in animals without pancreatic insufficiency. In the face of decreased pancreatic proteolysis, the 3H/14C ratio was 2.3-3.1, similar to that of proteins with a slow half life. 4. Estimates of relative synthetic rates of large brush border proteins were lower than normal in pancreatectomized animals, but were constant over the period of the labelling experiment. The high enzyme levels in the face of lower synthetic rates confirms that, at the new steady rate, degradation rates must be slower for large brush border proteins in pancreatic insufficiency. 5. In vitro, using purified brush borders, unfractionated pancreatic enzymes were found to remove sucrase, maltase and lactase, but not alkaline phosphatase and trehalase. The enzyme most potent in this respect was the pancreatic protease, elastase. Non-proteolytic enzymes (amylase, lipase, phospholipase A) were inactive in removing enzyme from the brush border. The addition of elastase to pancreatectomized animals in vivo restored the rapid turnover rate of large brush border proteins. 6. A model is thus proposed for the normal catabolism of some large intestinal brush border proteins. It is suggested that the surface of intestinal absorptive cells is being constantly remodelled, and that certain surface enzymes are in part removed from the membrane by the action of pancreatic proteases. A possible special role for elastase is suggested.
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PMID:The possible role of pancreatic proteases in the turnover of intestinal brush border proteins. 114 88

Approximately 10% of the alkaline phosphatase activity in human kidney is derived from the intestinal-type alkaline phosphatase isoform, which can be differentiated from adult intestinal alkaline phosphatase by selective reactivity with monoclonal antibodies. The NH2-terminal sequence of the renal intestinal-type alkaline phosphatase was shown to be identical to sequences of the adult and meconial alkaline phosphatases except for the NH2-terminal valine residue, which is missing in the renal intestinal-type enzyme. Incubation of purified meconial alkaline phosphatase with kidney homogenate resulted in removal of the NH2-terminal valine residue, indicating the presence of aminopeptidases in kidney that catalyze this hydrolysis. Furthermore, the oligosaccharide chains of the renal intestinal-type alkaline phosphatase were shown to differ from those of meconial and adult intestinal alkaline phosphatases, as revealed by lectin affinity chromatography. The heterogeneity of the intestinal-type alkaline phosphatase can therefore be generated both by partial peptide bond hydrolysis and differences in glycosylation.
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PMID:Chemical nature of intestinal-type alkaline phosphatase in human kidney. 145 95

Experiments were carried out to study the digestibility of a cassava (gari) diet and its effect on growth in young male dogs. Three groups of dogs were fed on diets with rice (control), cassava (gari), and rice + cyanide respectively as the carbohydrate source. Each diet contained 130 g crude protein (nitrogen x 6.25)/kg, was supplemented with vitamins and minerals, and was fed for 14 weeks. Variables measured were body-weight gain, bone growth, plasma alkaline phosphatase (EC 3.1.3.1) activity, total serum 3,5,3'-triiodothyronine (T3) and some plasma free amino acids. The apparent digestibilities of dry matter, protein and fat were not significantly different in the three groups, but the digestibility of gari fibre was significantly lower than the digestibility of rice fibre when fed to dogs (P less than 0.05). Proximate analysis of the faeces showed that the group of dogs fed on the gari diet had faeces which had a significantly higher moisture content than the faeces of the other groups (P less than 0.05), and also a significantly higher fibre content (P less than 0.05). There was no significant difference in body-weight gain and bone growth between the control and gari-fed groups of dogs, but these variables were significantly lower in the dogs fed on the rice + cyanide diet (P less than 0.05). At the end of the 14-week experimental period total serum T3 and plasma alkaline phosphatase activity were not significantly different between the control group of dogs and the gari-fed group, but were significantly lower in the rice + cyanide group. Plasma free methionine, leucine, isoleucine and valine concentrations were higher in the rice + cyanide group of dogs than in the control group and the gari group, indicating that these amino acids were accumulating and not being utilized for protein synthesis and growth to the same extent in the rice + cyanide group of dogs as in the other groups. It was concluded that the digestibilities of cassava starch and rice starch were the same in the dog but that rice fibre was more digestible in the dog than cassava fibre. It was also concluded that growth proceeded normally when a balanced gari diet or a balanced rice diet containing 130 g crude protein/kg was fed to dogs, but growth was retarded when a balanced rice + cyanide diet containing 130 g crude protein/kg was fed to dogs because total serum T3 concentration became greatly depressed.
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PMID:Digestibility of a nutritionally-balanced cassava (Manihot esculenta Crantz) diet and its effect on growth in young male dogs. 166 68

Nascent precursors of phosphatidylinositol-glycan (PI-G)-linked membrane proteins contain a hydrophobic COOH-terminal sequence of 15-30 residues that is eliminated during processing to yield a newly exposed COOH terminus to which the PI-G moiety is added. There is no consensus as to the primary structure of the terminal peptide but there is a specific requirement for the amino acid destined to become the COOH terminus. In nascent human placental alkaline phosphatase (PLAP), the PI-G tail is attached to Asp-484. Site-directed mutants with glycine, alanine, cysteine, serine, or asparagine (category I) at residue 484 become PI-G tailed, appear in the plasma membrane, and are enzymatically active when expressed in COS cells. Although mutants with glutamic acid, glutamine, proline, tryptophan, leucine, valine, phenylalanine, threonine, methionine, and tyrosine (category II) are expressed equally well, only small amounts appear on the plasma membrane. Furthermore, they are not PI-G tailed and have little alkaline phosphatase activity. Studies with truncated PLAP-489 rule out nonspecific conformational changes in category II mutant proteins as a reason for their failure to be processed in COS cells and point to a specific COOH-terminal processing enzyme. Direct evidence that the selectivity for category I amino acids is enzymatically determined was obtained in a cell-free translation/processing system by using rabbit reticulocyte lysate and CHO cell rough microsomal membranes. In this in vitro system, both category I and category II mutants of PLAP-513 were translated, glycosylated, and cleaved by NH2-terminal signal peptidase. However, an additional and selective cleavage at residue 484 was observed only with category I mutants.
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PMID:Selectivity at the cleavage/attachment site of phosphatidylinositol-glycan anchored membrane proteins is enzymatically determined. 170 Apr 20

Many proteins are now known to be anchored to the plasma membrane by a phosphatidylinositol-glycan (PI-G) moiety that is attached to their COOH termini. Placental alkaline phosphatase (PLAP) has been used as a model for investigating mechanisms involved in the COOH-terminal processing of PI-G-tailed proteins. The COOH-terminal domain of pre-pro-PLAP provides a signal for processing during which a largely hydrophobic 29-residue COOH-terminal peptide is removed, and the PI-G moiety is added to the newly exposed Asp-484 terminus. This cleavage/attachment site was subjected to an almost saturation mutagenesis, and the enzymatic activities, COOH-terminal processing, and cellular localizations of the various mutant PLAP forms were determined. Substitution of Asp-484 by glycine, alanine, cysteine, asparagine, or serine (category I) resulted in PI-G-tailed and enzymatically active proteins. However, not all category I mutant proteins were PI-G tailed to the same extent. Pre-pro-PLAP with other substituents at position 484 (threonine, proline, methionine, valine, leucine, tyrosine, tryptophan, lysine, glutamic acid, and glutamine; category II) were expressed, as well as the category I amino acids, but there was little or no processing to the PI-G-tailed form, and this latter group exhibited very low enzyme activity. The bulk of the PLAP protein produced by category II mutants and some produced by category I mutants were sequestered within the cell, apparently in the endoplasmic reticulum (ER). Most likely, certain amino acids at residue 484 are preferred because they yield better substrates for the putative "transamidating" enzyme. In transfected COS cells, at least, posttranslational PI-G-tail processing does not go to completion even for preferred substrates. Apparently PI-G tailing is a requisite for transport from the ER and for PLAP enzyme activity. Proteins that are not transamidated are apparently retained in the ER in an inactive conformation.
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PMID:Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase. 215 84

We have examined the hydrophobicity component of signal peptide function using polymeric sequences in combination with cassette mutagenesis. Using homopolymeric units of either isoleucine, leucine, valine or alanine to replace the natural core segment of the Escherichia coli alkaline phosphatase signal peptide, the hydrophobicity requirements for export and processing were delineated. The transport properties of these mutants demonstrated that the net hydrophobicity determines the total extent of precursor processing, while a high mean hydrophobicity/residue is critical for complete, rapid processing and translocation. Moreover, alkaline phosphatase was converted from a periplasmic to an active membrane-anchored protein via a signal containing 20 leucine residues. This application of polymeric sequences allows systematic comparisons to be made, unambiguously revealing the hydrophobicity requirements governing specific steps in the transport process.
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PMID:Polymeric sequences reveal a functional interrelationship between hydrophobicity and length of signal peptides. 215 63

The effect of lithium and other antipsychotic drugs on the renal function in patients with manic-depressive disorders has been investigated. Thirty-four patients (5 males and 29 females) treated with lithium and 21 patients (6 males and 15 females) on other antipsychotic drugs were studied. A control group of 10 persons consisting of healthy subjects, all of whom were taking no medication was also studied. No significant differences in the treatment duration were present between the patients investigated. Although few patients on lithium had glomerular filtration reduced, no statistically significant difference in creatinine clearance was found between the groups. None of the patients had a disturbance in the reabsorption of glucose, amino acids (histidine, lysine, valine, glutamine, glycine, serine, taurine, threonine, alanine, isoleucine) and beta 2-microglobulin. Patients treated with lithium had a significantly reduced urine concentration and higher daily diuresis than did the other two studied groups. A significantly higher overnight elimination of alkaline phosphatase was found in a group of patients taking other antipsychotic drugs. The attained results suggest tubular lesions in patients with manic-depressive psychosis occurring in the association with the prophylactic use of lithium and, at same time, the possibility of the other in association with the other antipsychotic drugs.
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PMID:[Effect of long-term use of lithium on kidney function]. 236 20

We examined the cytoprotective action of individual amino acids in isolated perfused kidneys during perfusion with either 10 mM lactate or 5 mM glucose. In the absence of amino acids inulin clearance fell rapidly, whereas fractional excretion of phosphate, lactate, or glucose increased to more than 30%; lactate dehydrogenase was released into perfusate and alkaline phosphatase into the urine. Functional deterioration was less in kidneys from rats rendered chronically water diuretic by drinking 5% glucose. Adding 5 mM glycine, L-alanine, beta-alanine, or D-alanine to the perfusate also prevented functional deterioration and release of enzymes. Glycine perfusion increased total phospholipid per microgram DNA by 6%. Aspartate, glutamate, glutamine, taurine, isoleucine, leucine, and valine were not protective. Serine, proline, and alpha-aminoisobutyric acid had small protective effects. Micropuncture measurements of proximal tubular free- and stop-flow pressures showed no effect of L-alanine on glomerular hemodynamics. L-Alanine increased oxygen consumption by both glucose- and lactate-perfused kidneys and increased gluconeogenesis by lactate-perfused kidneys but did not alter renal ATP content or energy charge. L-Alanine was not consumed during 70 min of perfusion and its protective action was not inhibited by blocking transamination with 0.5 mM amino-oxyacetate. The protective action of glycine was not inhibited by blocking glycine metabolism with 0.1 mM cysteamine. Thus the beneficial effects of L-alanine and glycine do not require their metabolism. These observations suggest that small neutral amino acids prevent tubular disruption through their physicochemical effects, which can stabilize membrane protein tertiary structure.
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PMID:Mechanisms of perfused kidney cytoprotection by alanine and glycine. 237 94


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