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)

Degradation of the 2'-phosphates, 3'-phosphates, 5'-phosphates, 2':3'-cyclic phosphates, 3':5'-cyclic phosphates, and 5'-(p-nitrophenylphosphates) of adenosine, guanosine, cytidine, and uridine catalyzed by Fusarium phosphodiesterase-phosphomonoesterase was followed by means of high performance liquid chromatography. All the nucleotides were susceptible to the enzyme to a greater or lesser degree, and the kinetic constants, Km and kcat, were determined at pH 5.3 and 37 degrees C. These constants were affected by both the nucleoside moiety and the position of the phosphate. Judged from kcat/Km, the 3'-phosphates, 2':3'-cyclic phosphates, and 5'-(p-nitrophenylphosphates) were good substrates, whereas the 2'-phosphates, 5'-phosphates, and 3':5'-cyclic phosphates were poor substrates except for adenosine 2'-phosphate, adenosine 5'-phosphate, and cytidine 5'-phosphate, which were hydrolyzed relatively easily. Among the phosphodiesters, the 2':3'-cyclic phosphates of adenosine, guanosine, and cytidine; and the 3':5'-cyclic phosphates of adenosine and cytidine were degraded into nucleoside and inorganic phosphate without release of intermediary phosphomonoester into the medium. Other phosphodiesters were degraded stepwise releasing definite intermediates.
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PMID:Kinetic studies on degradation of nucleotides catalyzed by phosphodiesterase-phosphomonoesterase from Fusarium moniliforme. 609 92

The chemical synthesis of thiazole-4-carboxamide adenine dinucleotide (TAD), previously identified as the active anabolite of the oncolytic 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), has been achieved by three different approaches: (1) incubation of adenosine 5'-monophosphate (AMP) and 2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-monophosphate (TRMP) with excess DCC in aqueous pyridine, (2) reaction of adenosine 5'-phosphoromorpholidate with TRMP in pyridine, and (3) reaction of adenosine-5'-phosphoric di-n-butylphosphinothioic anhydride with TRMP in the presence of AgNO3. While the first approach produced only traces of TAD, the last two afforded 31 and 16% yields, respectively, of isolated TAD. The synthetic material was indistinguishable from biosynthesized TAD as judged by its HPLC behavior, NMR, UV and mass spectra, enzymatic resistance to alkaline phosphatase and susceptibility to venom phosphodiesterase, IMP dehydrogenase inhibitory activity, and cytotoxicity. TAD and TR were equally effective against murine P388 leukemia when employed at equimolar doses.
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PMID:Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase. 613 56

The interaction of 5'-deoxy-5'-thioadenosine 5'-monophosphate (A(S)MP) and 5'-deoxy-5'-thioinosine 5'-monophosphate (I(S)MP) with snake venom, 5'nucleotidase, and calf intestinal mucosa alkaline phosphatase has been characterized. The substrates, A(S)MP and I(S)MP, are analogs of adenosine 5'-monophosphate and inosine 5'-monophosphate in which sulfur replaces oxygen as the bridge between the 5'-carbon of the ribose and the phosphorous. The P-S bond of both A(S)MP and I(S)MP was hydrolyzed by alkaline phosphatase producing the corresponding thionucleoside as a reaction product. The Km for A(S)MP was 270 microM and the V for alkaline phosphatase was 110 nmol/min/mg (8% of the V for AMP), whereas the corresponding values for I(S)MP were 300 microM and 530 nmol/min/mg protein, respectively. In contrast, 5'-nucleotidase did not catalyze hydrolysis of either A(S)MP or I(S)MP. A(S)MP and I(S)MP were competitive inhibitors of the 5'-nucleotidase hydrolysis of AMP and IMP, respectively, with Ki values of 975 and 13 microM. Decreasing the pH of the reaction from 8.1 to 7.1 lowered the Ki for I(S)MP by 100-fold, to a value of 0.15 microM.
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PMID:5'-deoxy-5'-thioanalogs of adenosine and inosine 5'-monophosphate: studies with 5'-nucleotidase and alkaline phosphatase. 629

Extensive kinetic studies of bovine intestinal 5'-nucleotide phosphodiesterase as a function of pH have confirmed and amplified the catalytic mechanism previously proposed on the basis of isolation of a covalent phosphorylated intermediate (Landt, M., and Butler, L.G. (1978) Biochemistry 17, 4130-4135). An enzyme-ionizing group with apparent pKa = 6.85 controls the rate-determining step. Electrostatic interactions between anionic substrate and two or more ionic groups on the enzyme have a major role in substrate binding. Binding of strongly inhibitory 5'-AMP is controlled by an ionizing group, probably on the enzyme, with pKa less than or equal to 5.9. At pH 6.0, imidazole is a classic uncompetitive inhibitor, in agreement with independent evidence that it stabilizes the covalent intermediate form of the enzyme. KI values for phosphonate analogs, which are competitive inhibitors, indicate that phosphodiesterase binds its products and product analogs more strongly than it binds substrate analogs. Some of the results presented here can be interpreted as indicating that 5'-nucleotide phosphodiesterase is the evolutionary precursor of alkaline phosphatase, with which it has many structural and catalytic properties in common, and which is found in relatively large amounts in the same tissue.
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PMID:The catalytic mechanism of bovine intestinal 5'-nucleotide phosphodiesterase. pH and inhibition studies. 630 65

In this communication, we propose a method for the determination in human serum of fructose 1,6-bisphosphatase based on parallel measurements of enzyme activities in presence of 1-p-bromotetramisole oxalate and adenosine 5'-monophosphate. The employment of these specific inhibitors renders the discrimination between specific and non-specific activities feasible. A regression analysis identifies fructose 1,6-bisphosphatase (EC 3.1.3.11) as the origin of the specific and alkaline phosphatase (EC 3.1.3.1) as the source of the non-specific fructose 1,6-bisphosphate dephosphorylating activities. This procedure lends itself to the diagnosis using serum samples of 'piecemeal' necrosis in liver disease.
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PMID:Fructose 1,6-bisphosphatase in the diagnosis of chronic hepatitis. I. Activity measurements of fructose 1,6-bisphosphatase in human serum. 632 Oct 61

The experiments were carried out with 4-week-old broiler birds given a ration that was balanced in terms of basic nutrients. Following decapitation inverted intestinal sacs were prepared from the proximal part of the jejunum the incubation of which lasted 40 min. To elucidate the effect of folic acid on the transport of 35S-methionine the acid was used in a conc. of 4 X 10(-6). Studied was also the effect of replacing the sodium ion (148 mEq/l) in the incubation solution with equivalent amount of the potassium ion, and the incorporation into the same solution of monoiodine-acetic acid (10(-3)M) as it affects the transmembrane transport of methionine. The flasks with the sacs of each group of birds contained 10microCi 35S-methionine each. The content of cyclic 3', 5'-adenosine-monophosphate (cAMP), the SH-groups, and the activity of alkaline phosphatase in the jejunal mucosa were determined. Results showed that folic acid at 4 X 10(-6)M stimulated dependably both the transport and the incorporation of 35S-methionine into the erythrocytes. These processes were inhibited when monoiodine-acetic acid at 10(-3)M was added to the incubation solution. Identic negative effect was produced also when K+ was used instead of Na+. Folic acid was said to raise the content of cAMP, SH-groups, and the activity of alkaline phosphatase in the jejunal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of folic acid on 35S-methionine transport in vitro]. 666 33

2'(3')-O-DL-Alanyl (Ip)5I was synthesized by a new method. An alanine ortho ester of inosine 5'-phosphate was added to (Ip)4I using the ATP-independent reaction of T4 RNA ligase, and the product was converted smoothly to the desired ester. The enzymic reverse transfer reaction was conveniently suppressed by the dephosphorylation of the adenosine 5'-phosphate coproduct, catalyzed in situ by alkaline phosphatase.
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PMID:Synthesis of 2'(3')-O-DL-alanyl hexainosinic acid using T4 RNA ligase: suppression of the enzymic reverse transfer reaction by alkaline phosphatase. 685 53

The observation that NAD inhibits sodium-dependent phosphate (P) uptake by the luminal brush border membrane (BBM) of the proximal tubule prompted us to examine the specificity and mechanism of this process. Addition of 10(-5) M NAD to the perfusate of isolated perfused rabbit proximal straight tubules inhibited lumen-to-bath P flux by approximately 50%. ADP-ribose had an identical effect, whereas nicotinamide had no effect. ADP and 5'-AMP (10(-5) M) also inhibited P flux. Na-dependent uptake of 32P by rabbit BBM vesicles was inhibited by 0.1-0.3 mM NAD, ADP-ribose, ADP, ATP, 5'-AMP, and GDP, which were preincubated with the vesicles for 30 min. The kinetics of inhibition showed an apparent increase in the Km for P but no change in Vmax. These findings are consistent with "competitive inhibition." The nucleotides inhibited P uptake even when BBM alkaline phosphatase was inhibited by 96% with 10 mM theophylline. Evidence of nonspecific phosphatase activity was present, since incubation of BBM with 0.1 mM solution of nucleotides for 30 min resulted in an elevation of free P in the medium of approximately 0.15-0.22 mM. Correction of 32P specific activity for this change resulted in values for Km and Vmax that were not significantly different from control. The "competitive inhibition" could thus be ascribed to an isotope-dilution effect. There was no evidence to suggest that NAD caused ADP-ribosylation of the luminal membrane. These studies indicate that adenine and guanine nucleotides do not inhibit P transport by a direct action on the luminal membrane of the proximal tubule but do inhibit lumen-to-bath P flux in isolated perfused proximal tubules at concentrations of 10(-5) M. Since there is no direct inhibitory effect of these compounds at the level of the BBM, it is possible that they inhibit P transport by altering some event subsequent to the transfer of P across the luminal membrane.
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PMID:Nucleotide inhibition of phosphate transport in the renal proximal tubule. 688 41

1. The addition of 50 000g cytosol preparations of isolated human platelets, cultured rat osteogenic sarcoma or cultured bone cells to particulate preparations of adenylate cyclase, from the same or unrelated tissues, caused marked enhancement of the hormone-stimulated enzyme activities. 2. The degree of enhancement obtained by addition of the cytosol preparations was similar to that observed on addition of GTP. 3. The enhancing activity of the three cytosol types was found to be sensitive to digestion by trypsin and alkaline phosphatase, partially heat-labile and partially inactivated by exposure to charcoal. 4. Gel filtration studies indicated an apparent molecular weight of 20 000--30 000. Further, the 20000-30000-mol.wt. fractions obtained by gel filtration could enhance the adenylate cyclase activity of particulate preparations derived from unrelated cell types. 5. The results suggest a common or similar adenylate-cyclase-enhancing factor or factors, protein in nature, present in the three cytosol types.
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PMID:Properties of a factor in cytosol that enhances hormones-stimulated adenylate cyclase activity. 693 Sep 68

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.
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PMID:Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells. 693 60


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