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)

Seventy-one male and 52 female F 344 rats with leukemia used as controls in the 30-month inhalation studies were characterized by hematological and clinico-biochemical findings. Hematological findings revealed that the leukocyte count, mean corpuscular volume, and mean corpuscular hemoglobin increased in both sexes of leukemic rats showing profound anemia, while the platelet count, erythrocyte count, hematocrit, and hemoglobin concentration decreased. In these rats, the serum levels of low density lipoprotein, free cholesterol, total bilirubin, blood urea nitrogen, and triglyceride and the activities of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, creatine phosphokinase, alkaline phosphatase, and lactate dehydrogenase increased markedly and the level of high density lipoprotein, the oxygen partial pressure, and the cholinesterase activity decreased. Clinical signs such as decrease in redness of the eyes, decrease in body weight, abdominal distension, staining of the public region, and debility were seen in most leukemic animals. These clinical signs and hematological and clinico-biochemical findings may be helpful in diagnosis of leukemia in long-term experiments.
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PMID:Hematological and clinico-biochemical characteristics of leukemia in Fischer 344 rats. 150 22

Alkaline phosphatase was the first zinc enzyme to be discovered in which three closely spaced metal ions (two Zn ions and one Mg ion) are present at the active center. Zn ions at all three sites also produce a maximally active enzyme. These metal ions have center-to-center distances of 3.9 A (Zn1-Zn2), 4.9 A (Zn2-Mg3), and 7.1 A (Zn1-Mg3). Despite the close packing of these metal centers, only one bridging ligand, the carboxyl of Asp51, bridges Zn2 and Mg3. A crystal structure at 2.0-A resolution of the noncovalent phosphate complex, E.P, formed with the active center shows that two phosphate oxygens form a phosphate bridge between Zn1 and Zn2, while the two other phosphate oxygens form hydrogen bonds with the guanidium group of Arg166. This places Ser102, the residue known to be phosphorylated during phosphate hydrolysis, in the required apical position to initiate a nucleophilic attack on the phosphorous. Extrapolation of the E.P structure to the enzyme-substrate complex, E.ROPO4(2-), leads to the conclusion that Zn1 must coordinate the ester oxygen, thus activating the leaving group in the phosphorylation of Ser102. Likewise, Zn2 appears to coordinate the ester oxygen of the seryl phosphate and activate the leaving group during the hydrolysis of the phosphoseryl intermediate. Both of these findings suggest that there may be a significant dissociative character to each of the two displacements at phosphorous catalyzed by alkaline phosphatase. A water molecule (or hydroxide) coordinated to Zn1 following formation of the phosphoseryl intermediate appears to be the nucleophile in the second step of the mechanism. Dissociation of the product phosphate from the E.P intermediate is the slowest, 35 s-1, and therefore the rate-limiting, step of the mechanism at alkaline pH. Since the determination of the initial crystal structure of alkaline phosphatase, two other crystal structures of enzymes involved in phosphate ester hydrolysis have been completed that show a triad of closely spaced zinc ions present at their active centers. These enzymes are phospholipase C from Bacillus cereus (structure at 1.5-A resolution) (43) and P1 nuclease from Penicillium citrinum (structure at 2.8-A resolution) (74). Both enzymes hydrolyze phosphodiesters. Substrates for phospholipase C are phosphatidylinositol and phosphatidylcholine, while P1 nuclease is an endonuclease hydrolyzing single stranded ribo- and deoxyribonucleotides. P1 nuclease also has activity as a phosphomonoesterase against 3'-terminal phosphates of nucleotides. The Zn ions in both enzymes form almost identical trinuclear sites.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structure and mechanism of alkaline phosphatase. 152 73

Growth failure is a major complication of chronic hypoxemia, as seen in infants and children with cyanotic congenital heart disease. To determine whether chronic hypoxemia during infancy affects the gastrointestinal tract, we examined small intestinal growth and digestive enzyme activities in chronically hypoxemic newborn lambs and in age-matched controls. Chronic hypoxemia was produced by placing an inflatable occluder around the main pulmonary artery and performing a balloon atrial septostomy. Aortic oxygen saturation was reduced to 60-74% for 2 wk, after which the small intestine was removed for analysis. During chronic hypoxemia, somatic growth rate was decreased to 60% of control (hypoxemic, 135 +/- 20 versus control, 216 +/- 26 g/d, p less than 0.02). No differences in caloric intake were found (hypoxemic, 129 +/- 4 versus control, 128 +/- 4 kcal/kg/d). Chronic hypoxemia did not alter small intestinal growth, as measured by jejuno-ileal weight, jejuno-ileal length, mucosal weight, or mucosal protein or DNA contents. However, sp act of lactase, the principal disaccharidase of the infant lamb intestine, were significantly decreased (hypoxemic, 0.08 +/- 0.01 versus control, 0.146 +/- 0.03 units of enzyme activity/mg DNA, p less than 0.05), as were the total small intestinal contents of lactase (hypoxemic, 61.7 +/- 7.0 versus control, 120.6 +/- 21.7 units of enzyme activity, p less than 0.01). There also were decreases in specific and total activities of other digestive enzymes such as maltase, amino-oligopeptidase, and alkaline phosphatase in hypoxemic intestine that did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in postnatal intestinal function during chronic hypoxemia. 156 Oct 8

In order to investigate the function of Asp-327, a bidentate ligand of one of the zinc atoms in Escherichia coli alkaline phosphatase, and the importance of this zinc atom in catalysis, site-specific mutagenesis was used to convert Asp-327 to either asparagine or alanine. The 10(7)-fold decrease in the kcat/Km ratio observed for the Asp-327----Ala enzyme compared to the wild-type enzyme indicates that the side chain of Asp-327 is important for zinc binding at the M1 site. However, only one of the two carboxyl oxygens of Asp-327 is essential for zinc binding, since the Asp-327----Asn enzyme shows approximately the same hydrolysis activity as the wild-type enzyme. The fact that the enzymatic activity of this mutant enzyme shows a dependence on zinc concentration suggests that the other carboxyl oxygen or the negative charge on the side chain of Asp-327 is important in binding of the zinc at the M1 site. However, the zinc hydroxyl must still be appropriately positioned to attack the phosphoserine in the Asp-327----Asn enzyme; therefore, the negative charge and at least one carboxyl oxygen of the side chain are not directly involved in positioning or deprotonating the zinc hydroxyl. 31P NMR studies indicate that the Asp-327----Asn enzyme exhibits transphosphorylation activity at both pH 8.0 and pH 10.0, but at a reduced level compared to the wild-type enzyme. The biphasic production of 2,4-dinitrophenylate in the pre-steady-state kinetics of the mutant enzymes at pH 5.5 suggests that the breaking of the phosphoenzyme covalent complex is rate-limiting for both mutant enzymes. These results suggest that the main function of the zinc atom at the M1 site in catalysis involves decomposition of the phosphoenzyme covalent complex and that it may be important in helping to stabilize the alcohol leaving group.
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PMID:The importance of aspartate 327 for catalysis and zinc binding in Escherichia coli alkaline phosphatase. 164 10

A number of phosphorylated thiosugars have been prepared and tested as substrates for metabolic reactions. 6-Thioglucose-6-P is readily synthesized by reaction of 6-tosylglucose with trisodium thiophosphate at pH 10 in aqueous solution; the product has only sulfur between carbon and phosphorus. When ethyl glycerate is tosylated and treated similarly with thiophosphate, a 5:1 mixture of 3-thioglycerate-3-P and the 2-isomer is formed. 6-Thioglucose-6-P is converted by glycolytic enzymes to triose phosphates, 3-thioglycerol-3-P and 3-thioglycerate-3-P, and is oxidized by enzymes of the hexose monophosphate shunt to 5-thioribulose-5-P, which can be converted via phosphoribulokinase and ribulose-bis-P carboxylase into 3-P-glycerate and 3-thioglycerate-3-P. For most of the non-phosphoryl-transferring enzymes there are only moderate effects on Vmax and Km. Phosphoglucoisomerase, however, is very sensitive to the sulfur for oxygen change, with Vmax decreasing 60-fold and Km increasing 15-fold. Surprisingly, phosphoribulokinase has a V/K value for 5-thioribulose-5-P that is over 3 orders of magnitude less than for ribulose-5-P. 6-Thio-glucose-6-P was found to be a substrate for several enzymes that transfer the phosphoryl group. It is as good a substrate for alkaline phosphatase as glucose-6-P, and with phosphoglucomutase it is converted to 6-thioglucose-1-P with a rate that is 11% of the rate of reaction of glucose-1-P, with a Keq value of 45.6. The free energy of hydrolysis of the phosphorylated thiol is thus -7.2 kcal/mol at pH 7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphorylated thiosugars: synthesis, properties, and reactivity in enzymatic reactions. 164 86

The intestinal transport of D-xylose was studied during subchronic poisoning of male Wistar rats with the oral administration of potassium nitrate and sodium nitrite. The metabolic parameters of small intestine mucosa were determined one hour after xylose administration, i.e., Na+/K(+)-ATPase, alkaline phosphatase, oxygen consumption, and lactic acid level. Nitrite reduced the absorption of xylose and decreased the activity of Na+/K(+)-ATPase and alkaline phosphatase. No effect of sodium nitrite was demonstrated on the aerobic metabolism of intestinal mucosa with an increased lactic acid level. Potassium nitrate did not effect the processes of intestinal absorption of xylose nor the metabolic parameters of small intestine mucosa.
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PMID:The effect of subchronic poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. 165 32

The intestinal transport of D-xylose was studied during the acute poisoning of male Wistar rats with orally administered potassium nitrate and sodium nitrite. At the peak of xylose absorption, the metabolic parameters of Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level were determined in the small intestine mucosa. Nitrite in a dose of 80 mg NaNO2/kg b.w. increased the permeability of gastric mucosa for D-xylose and raised the uptake of oxygen by the small intestine mucosa. No changes were observed in the activity of Na+/K(+)-ATPase and alkaline phosphatase. A dose of 10 mg NaNO2/kg b.w. was not followed by increased absorption of this sugar. It was also demonstrated that potassium nitrate had no effect on the process of intestinal absorption of D-xylose and failed to change the determined metabolic parameters of the small intestine mucosa.
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PMID:The effect of acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. 165 33

The intestinal absorption of D-xylose was studied during the subchronic poisoning of male Wistar rats with orally administered potassium nitrate and sodium nitrite associated with exercise; running on a moving track during the last two weeks of poisoning. The metabolic parameters of Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level in the small intestine mucosa were determined one hour after D-xylose treatment. Exercise increased the toxicity of potassium nitrate and sodium nitrite. The experiment demonstrated post-exercise reduction of D-xylose absorption and decrease activity of Na+/K(+)-ATPase and alkaline phosphatase. Exercise caused transient hypoxia of the small intestine, which was observed only in the groups subjected to exercise on the day of the determinations.
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PMID:The effect of exercise associated with subchronic poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. 165 34

The intestinal absorption of D-xylose was studied during acute poisoning of male Wistar rats receiving intragastrically potassium nitrate and sodium nitrite and small intestine perfusion with these compounds. The metabolic parameters, Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level, were assessed in the small intestine mucosa one hour after administration of these compounds. Exercise was demonstrated to reduce the intestinal absorption of D-xylose, to raise the level of lactic acid, and to increase the oxygen uptake by the small intestine mucosa, but caused no changes in the activity of Na+/K(+)-ATPase or alkaline phosphatase. Also, exercise failed to change the direction of the toxic effects of sodium nitrite but increased potassium nitrate toxicity as evidenced by reduced absorption of D-xylose from the intestine despite lack of changes of the enzymes Na+/K(+)-ATPase and alkaline phosphatase in the mucosa.
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PMID:The effect of exercise associated with acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. 165 35

The biochemical parameters Na+/K(+)-ATPase, alkaline phosphatase, oxygen consumption, and lactic acid level were evaluated in the small intestine mucosa of male Wistar rats during in situ perfusion of the rat with sodium nitrite. Sodium nitrite was poorly absorbed (10% of the administered dose), but it inhibited the activity of Na+/K(+)-ATPase and alkaline phosphatase. It had no effect on the lactic acid level, pointing to normal oxygen in the intestine, evidently reducing the utilization of oxygen by this tissue. Using metabolism inhibitors added to the perfusion fluid in the concentrations: ouabaine 0.1 mM, NaN3 (sodium azide) 1 mM, L-phenylalanine 50 mM and during functional ischaemia of the intestine produced by occlusion of the superior mesenteric artery for the time of the perfusion, it was possible to find the site of action and the direction of the toxic influence of sodium nitrite.
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PMID:Studies on the mechanism of the toxic action of sodium nitrite on intestinal absorption in rats. 165 36


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