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)

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

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

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

An alkaline phosphatase signal sequence optimized for formation of a hydrophobic alpha-helix functions very efficiently in the transport process. This mutant contained a core region comprised of 9 consecutive leucine residues (Kendall, D. A., Bock, S. C., and Kaiser, E. T. (1986) Nature 321, 706-708). We have now constructed a second mutant containing a decaisoleucine core region. Isoleucine was chosen because it is an isomer of leucine with comparable hydrophobicity but in synthetic peptides isoleucine favors beta-sheet formation. Surprisingly, this mutant precursor was also processed efficiently, and mature alkaline phosphatase was correctly targeted to the Escherichia coli periplasm. Since the effective length of a beta-strand is extended relative to an alpha-helix, conformational differences should be mirrored by the relative effectiveness of shortened polyisoleucine and polyleucine core regions. However, analysis of two additional mutants containing truncated segments of either polyleucine or polyisoleucine did not reveal any differences and both accumulate as precursors. We conclude that these mutants do not adopt critically different structures. This comparative analysis was facilitated by construction of a new plasmid, CASS3. This plasmid contains unique restriction sites flanking the DNA region coding for the signal sequence hydrophobic core segment. Consequently, the wild type core-encoding region can be readily replaced with synthetic oligonucleotides coding for new structural units and multiple amino acid substitutions can be made without the need for step-wise mutagenesis.
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PMID:A functional decaisoleucine-containing signal sequence. Construction by cassette mutagenesis. 328 84

Sixty-one patients with liver disorders receiving total parenteral nutrition (TPN) for about 14 postoperative days were divided into three groups based on the parenteral nutritional regimen. The influence of these TPN solutions on the liver function tests and the nutritional assessments, and the availability of the specially formulated amino acid solution were studied. Glucose alone as energy source was infused in Group Ia. The mixture of glucose and fructose was infused in Group Ib. In these patients (Group I), a commercially available amino acid solution was administered simultaneously. A specially formulated amino acid, rich in branched-chain amino acids but poor in aromatic amino acids was infused with the mixture of glucose and fructose in Group II. There was no remarkable elevation of blood glucose and lactate levels in all patients. Blood glucose levels in Group Ib were maintained lower than that in Group Ia. Except for serum alkaline phosphatase, no remarkable abnormality was observed in liver function tests. Body weight changes were less than 5% in each group. Average nitrogen balances were -44.5 mg/kg/day in Group Ia, -5.5 mg/kg/day in Group Ib, -51.5 mg/kg/day in Group II. While the abnormalities in serum amino acid pattern and molar ratio of leucine, isoleucine, and valine to phenylalanine and tyrosine tend to be more enhanced in Group I, these abnormalities returned to near normal in Group II during TPN. By multiple linear regression analyses, 45 kcal/kg/day of energy intake would be required to maintain nitrogen equilibrium and zero body weight change. And when nitrogen intakes were 159 mg/kg/day in Group Ia, 114 mg/kg/day in Group Ib, and 189 mg/kg/day in Group II at 45 kcal/kg/day in energy intake, nitrogen balances were expected to be equivalent. These results suggest that postoperative TPN is good for nutritional support in patients with liver disorders. And also, the combination of glucose and fructose has better effect on nitrogen balance. The postoperative TPN with a specially formulated amino acid solution may be a valuable way of maintaining the nutritional status as well as normal serum amino acid pattern in patients with liver disorders.
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PMID:Postoperative total parenteral nutrition in patients with liver disorders. 392 62

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
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PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18

A diagonal-electrophoresis method for the selective purification of serine phosphate peptides was applied to tryptic, chymotryptic and peptic digests of oxidized ovalbumin. This method is based on the release of the phosphate group bound to serine by treatment with alkaline phosphatase on paper. The identified serine phosphate peptides were purified by paper electrophoresis at pH6.5 and 2.0, dephosphorylation with bacterial alkaline phosphatase, and paper electrophoresis at pH2.0 again, in that order. The presence of two groups of serine phosphate peptides was apparent from the amino acid composition. One group contained no lysine, cysteic acid, proline, leucine or isoleucine (sequence 1) and the other had all those amino acids (sequence 2). Further degradation with subtilisin of those peptides and ;dansyl'-Edman sequence analysis established their partial sequences. The proposed sequences are as follows (with ;SerP' representing serine phosphate): sequence 1, -Ala-Gly-Arg-Glu-Val-Val-Gly-SerP-Ala-Glu-Ala-Gly-Asp-Val-Ala-Ala-Ser-(Val,Glx(2),Ser,Phe)-Arg-; sequence 2, -Asp-Lys-Leu-Pro-Gly-Phe-Gly-Asp-SerP-Ile-Glx-Ala-Glx-CySO(3)H-Gly-(Thr,Ser,Val)-(Asp,His,Val)-. The partial sequence of one of the phosphopeptides, Asp-(Glu,Ile,SerP), reported by Flavin (1954) was used to establish the proposed sequence 2.
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PMID:An application of diagonal electrophoresis to the selective purification of serine phosphate peptides. Serine phosphate peptides from ovalbumin. 488 Nov 41

Two major forms of human alpha-L-iduronidase have been individually purified over 175,000-fold to apparent homogeneity by sequential anion exchange, lectin affinity, and gel filtration chromatography. The two forms, initially designated as soluble and membrane-associated, were extracted from human lung in approximately equal amounts. Optimal solubilization of the membrane-associated form was facilitated by use of a non-ionic detergent or mannose 6-phosphate and saponin. Following detergent homogenization, the two forms were separated by anion exchange chromatography and then individually purified. The more electronegative form was membrane-associated, had a pI of approximately 5.9, and was selectively taken up (high uptake) by cultured Hurler syndrome fibroblasts; the more electropositive soluble form had a pI of about 6.6 and was incorporated into Hurler fibroblasts at a markedly lower rate (low uptake). After treatment with alkaline phosphatase, the pI values of both enzymes were about 7.8. Using 4-methylumbelliferyl-alpha-L-iduronide as substrate, the low and high uptake forms were each purified in milligram quantities to specific activities of 284,000 and 202,000 units/mg, respectively, with a combined yield greater than 35%. Each purified enzyme form migrated as a single protein band which also stained for enzymatic activity when electrophoresed in 7% native polyacrylamide disc gels at pH 4.3. By gel filtration, the high uptake form had an Mr = 85,000 whereas the Mr for the low uptake form was 68,000. Molecular weight estimates by analytical polyacrylamide gel electrophoresis were 82,000 and 70,000 for the high and low uptake forms, respectively. Rabbit anti-human low uptake alpha-L-iduronidase antibodies cross-reacted with the high uptake form as demonstrated by both immunotitration and Ouchterlony double immunodiffusion. Amino acid analysis revealed that the high uptake (higher molecular weight) form contained more arginine, glycine, alanine, glutamate or glutamine, leucine, isoleucine, histidine, and proline residues per molecule than the low uptake (lower molecular weight) form. Automated Edman degradation determined that the NH2-terminal residues of both forms were blocked. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high performance liquid chromatography demonstrated that each purified form was composed of several components; each post-high performance liquid chromatographic component retained catalytic activity and was immunologically cross-reactive with antibodies against the low uptake form.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human alpha-L-iduronidase. I. Purification and properties of the high uptake (higher molecular weight) and the low uptake (processed) forms. 642 18


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