Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purified phosphodiesterase-phosphomonoesterase was found to be composed of four isozymes with different isoelectric points. These isozymes, phosphodiesterase-phosphomonoesterases 1-4, were separated from one another by repeated isoelectric focusing. Very little difference in amino acid composition, enzymic properties or circular dichroism spectra was detected among the isozymes. Far-ultraviolet circular dichroism spectra showed that the enzyme contained about 10% alpha-helix and 40% beta-structure. Phosphodiesterase-phosphomonesterase is a glycoprotein, because it was adsorbed on concanavalin A-Sepharose 4B and gave a band of carbohydrate coincident with that of protein or enzymic activity on polyacrylamide disc gel electrophoresis. Carbohydrate analyses revealed that the enzyme contained 37 micron of N-acetylglucosamine and 358 micron of mannose per mg of protein. The carbohydrate contents of the four isozymes were almost the same.
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PMID:Phosphodiesterase-phosphomonesterases from Fusarium moniliforme. Separation and properties of four isozymes. 21 23

3'-Azido-2',3'-dideoxyuridine (AzdU, CS-87) is a potent inhibitor of human immunodeficiency virus replication in human peripheral blood mononuclear cells (PBMC) with limited toxicity for human bone marrow cells (BMC). In the present study, metabolism of AzdU was investigated in human PBMC and BMC after exposure of cells to 2 or 10 microM [3H]AzdU. 3'-Azido-2',3'-dideoxyuridine-5'-monophosphate (AzdU-MP) was the predominant metabolite, representing approximately 55 to 65% of intracellular radioactivity in both PBMC and BMC at all times. The AzdU-5'-diphosphate and -5'-triphosphate intracellular levels were 10- to 100-fold lower than the AzdU-MP levels and, of note, AzdU-5'-triphosphate was not detected in human BMC. Using anion exchange chromatography, a new peak of radioactivity, distinct from any known anabolites, was detected. This chromatographic peak was found to be resistant to alkaline phosphatase but was hydrolyzed by 5'-phosphodiesterase, yielding AzdU-MP. Incubation of [3H]AzdU and D-[1-14C]glucose in PBMC and BMC produced a double-labeled peak with the same retention time as the anabolite, suggesting formation of a hexose derivative of AzdU. A novel high performance liquid chromatography method was developed that allowed for the separation of nucleosides, nucleotides, and carbohydrate derivatives thereof. Using this highly specific method, the putative AzdU-hexose actually was separated into two chromatographic peaks. These novel metabolites were identified as 3'-azido-2',3'-dideoxyuridine-5'-O-diphosphoglucose and 3'-azido-2',3'-dideoxyuridine-5'-O-diphospho-N-acetylglucosamine. Following 48 hr of incubation with [3H] AzdU, as much as 20 and 30% of these AzdU metabolites accumulated in PBMC and BMC, respectively. When AzdU was removed from the cell cultures, intracellular AzdU diphosphohexose concentrations decayed in a monophasic manner, with an elimination half-life of 14.3 hr. By 48 hr, levels of 0.3 pmol/10(6) cells were still detected, reflecting a gradual anabolism of these metabolites. Elimination of AzdU-MP and AzdU-5'-diphosphate was characterized by a two-phase process, with a short initial half-life of 0.83 and 0.24 hr and a long terminal half-life of 14.10 and 8.24 hr, respectively. Similar diphosphohexoses of deoxyuridine (dUrd) were also detected in human PBMC and BMC after exposure to [3H]dUrd, suggesting that dUrd derivatives are metabolized in a similar manner. In summary, the discovery of novel metabolic pathways for dUrd analogs demonstrates that AzdU has unique metabolic features that may contribute to the low toxicity of this anti-HIV agent in human BMC and also affect its mechanism of action.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular metabolism of 3'-azido-2',3'-dideoxyuridine with formation of 5'-O-diphosphohexose derivatives by previously unrecognized metabolic pathways for 2'-deoxyuridine analogs. 225 Jun 66

Phosphoglycans from the cell wall of many strains of Streptococci contain terminal carbohydrate units linked by phosphodiester bridges to other residues of the glycans. In the immune response to phosphoglycans, the terminal carbohydrate-phosphate moieties function as antigenic determinants and induce the synthesis of antibodies with specificity for the glycosyl-phosphoryl units. It has now been found that such terminal carbohydrate units can be removed by treatment of the glycans with appropriate glycosidases. Thus, an almond beta-glucosidase releases glucose from a streptococcal Group D phosphoglycan with beta-glucosyl phosphate units, a jack bean N-acetyl-beta-glucosaminidase releases N-acetylglucosamine from a streptococcal Group L phosphoglycan with N-acetyl-beta-glucosaminyl phosphate units, and a rice alpha-glucosidase releases glucose from a yeast phosphoglycan with alpha-glucosyl phosphate units. The glycosidases also hydrolyze the hexose phosphates of the proper anomeric configuration and structure. The preparations of glycosidases used in this study exhibit specificity for single types of carbohydrate residues and are devoid of phosphatase and phosphodiesterase activities. The glycosidases act on glycosyl-phosphoryl linkages by a stereospecific mechanism and can therefore be used for the determination of the anomeric configuration of glycosyl-phosphoryl units of complex carbohydrates.
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PMID:The determination of the anomeric configuration of glycosyl-phosphoryl linkages of immunogenic phosphoglycans. 240 37

Chronic administration of the beta-adrenergic receptor agonist isoproterenol (5 mg/200 g animal for 10 days) resulted in rat parotid and submandibular gland hypertrophy, and it induced synthesis of a series of proline-rich proteins (PRPs) and glycoproteins. Treated parotid glands additionally exhibit an increase in activity for the Golgi membrane enzyme UDP-galactose; N-acetylglucosamine 4 beta-galactosyltransferase. A series of beta-receptor agonists and phosphodiesterase inhibitors were examined for their abilities to influence salivary gland protein biosynthesis in a fashion similar to that observed with chronic isoproterenol treatment. beta 1/beta 2-Adrenergic-receptor agonists exhibited the greatest effects on parotid gland hypertrophy and PRP biosynthesis. These beta-agonists were also able to increase 4 beta-galactosyltransferase activity, but they did not promote the synthesis of a 220,000 dalton glycoprotein. Terbutaline (beta 2-receptor agonist) induced parotid gland hypertrophy but was only able to induce protein biosynthesis at higher drug concentrations. Finally, methoxyphenamine was unable to produce the observed changes in protein synthesis even at increased drug dosages. The phosphodiesterase inhibitors (theophylline and caffeine) were able to induce de novo PRP biosynthesis at drug doses of 20 mg/200 g animal. However, while causing mild gland hypertrophy, there was no observable change in 4 beta-galactosyltransferase activity with either phosphodiesterase inhibitor. This same regimen of beta-receptor agonists was unable to induce submandibular gland hypertrophy, PRP or glycoprotein biosynthesis in the same animals. This was also true for the two phosphodiesterase inhibitors. Co-injection of a beta 1 antagonist along with isoproterenol blocked the above protein changes in both the submandibular and parotid glands, suggesting that the stimulation of protein synthesis takes place by beta 1-type receptors on the gland cell surfaces.
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PMID:Analysis of protein synthesis in rat salivary glands after chronic treatment with beta-receptor agonists and phosphodiesterase inhibitors. 286 70

The assay of fibroblast and leukocyte-N-acetylglucosaminylphosphotransferase with alpha-methylmannoside acceptor and commercially available UDP-[3H or 14C]N-acetylglucosamine donor was modified to yield low background and consequently high sensitivity and reliability comparable to those obtained with the synthetically made [beta-32P]UDP-N-acetylglucosamine donor. This was achieved by an additional elution step that removed free [3H or 14C]N-acetylglucosamine which appeared to be the breakdown product responsible for the high background. In addition, the [3H or 14C]N-acetylglucosamine-1-phospho-6-alpha-methylmannoside product of the transfer reaction was then isolated and, following desalting, could serve as a substrate for the assay of alpha-N-acetylglucosaminyl phosphodiesterase. Cell preparations of patients with I-cell disease and pseudo-Hurler polydystrophy demonstrated severe to moderate deficiency of transferase activity and normal phosphodiesterase activity toward the respective substrates labeled with 3H or 14C in the glucosamine moiety.
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PMID:Radiometric assays of N-acetylglucosaminylphosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase with substrates labeled in the glucosamine moiety. 609 58

The presence of phosphodiesterase IV has been demonstrated in the human fetal brain, liver and placenta as early as in the 6th week of intrauterine development. The enzyme activity in each tissue increases with gestation, being maximum at 18-21 wk and then decreases. The Km values of this enzyme for bis-(p-nitrophenyl)-phosphate hydrolysis in the brain, liver and placenta are 2.94 mM, 1.47 mM and 1.66 mM, respectively. Presence of sulfhydryl group in the active center of the placental enzyme has been demonstrated with the help of cationic study. EDTA inhibits the enzyme in all three tissues. Effect of concanavalin A reveals the absence or unexposition of glucose, mannose and N-acetylglucosamine moieties in the active site of the enzyme in each of the three tissues. Maximum enzyme activity has been found to be localized in the soluble supernatant fraction obtained on centrifuging the brain and liver homogenate at 105,000 x g and in 20,000 x g pellet of the placenta.
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PMID:Occurrence of phosphodiesterase IV in the developing human brain, liver and placenta. 628 89

The phosphomannosyl recognition marker of acid hydrolases, which mediates their translocation to lysosomes, has been shown to be synthesized in two steps. First, N-acetylglucosamine 1-phosphate is transferred to an acceptor mannose by UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, resulting in a phosphate group in diester linkage between the outer N-acetylglucosamine and the inner mannose. Next, an a-N-acetylglucosaminyl phosphodiesterase removes the N-acetylglucosamine, leaving the phosphate in monoester linkage with the underlying mannose residue. This exposed phosphomannosyl residue serves as the essential component of a recognition marker which leads to binding to high-affinity receptors and subsequent translocation to lysosomes. We propose that the first enzyme in this scheme, N-acetylglucosaminylphosphotransferase, catalyses the initial, determining step by which newly synthesized acid hydrolases are distinguished from other newly synthesized glycoproteins and thus are eventually targeted to lysosomes. The absence of this enzyme activity, as in inclusion-cell (I-cell) disease and pseudo-Hurler polydystrophy, precludes the receptor-mediated targeting of newly synthesized acid hydrolases to lysosomes. As a consequence, the enzymes are secreted into the extracellular milieu.
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PMID:Steps in the phosphorylation of the high mannose oligosaccharides of lysosomal enzymes. 629 19

Evidence is presented for the occurrence of two different non-specific nucleotide-sugar hydrolases in rat liver and other rat tissues. These two enzymes (I and II) were separated by chromatography on a 5'-AMP-aminohexyl-Sepharose column. Enzyme I is most probably identical with phosphodiesterase I (EC 3.1.4.1). Enzyme II appeared to be identical with an enzyme described in literature as 'CMP-sialic acid hydrolase' [Kean & Bighouse (1974) J. Biol. Chem. 249, 7813-7823], since almost all activity with CMP-N-acetylneuraminate as substrate was recovered in this enzyme fraction. CMP-N-acetylneuraminate was a poor substrate for Enzyme I, whereas deoxythymidine-5'-p-nitrophenyl phosphate and all nucleoside-diphosphosugars tested were good substrates for both Enzyme I and II. Therefore it is suggested that CMP-N-acetylneuraminate is used as an additional substrate to discriminate between the activities of Enzyme I and II in homogenates or membrane preparations. The various substrates appeared to be competitive inhibitors of each other, suggesting that, in each enzyme preparation, only one enzyme is responsible for the hydrolysis of the various substrates. The dissimilar properties of the two enzymes are substantiated by studying the subunit molecular masses (Enzyme I, 125 kDa; Enzyme II, 50-55 kDa), the sensitivity towards Triton X-100, Sarkosyl and sodium dodecyl sulphate and towards trypsin treatment. It is discussed whether the alpha-N-acetylglucosamine phosphodiesterase described by Varki & Kornfeld [(1981) J. Biol. Chem. 256, 9937-9943] is identical with one of the nucleotide-sugar hydrolases described here.
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PMID:On the presence of two non-specific nucleotide-sugar-hydrolysing enzymes in rat liver. 633 14

It has been demonstrated for the first time that GlcNAc-specific lectin from Solanum tuberosum induces the formation of haptenic sugar-resistant intercellular contacts (HSR-contacts) in platelet aggregation and does not induce stable neutrophil and lymphocyte aggregation. The formation of HSR-contacts in platelets was significantly impaired by the inhibitors of cAMP phosphodiesterase (papaverine) and arachidonic acid methabolism (indomethacin, aristolochic acid, and MK-886) as well as by the sulfhydryl reagent N-ethylmaleimide. The results obtained indicate that STA can be used to study the mechanisms of stable platelet aggregation, to screen drugs with potential antithrombotic activity, and to develop new cell engineering techniques.
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PMID:[The formation of stable aggrregates of human platelets induced by lectin from Solanum tuberosum]. 1796 23

Saccharomyces cerevisiae cells (strain W303-1A) treated with 5-fluorouracil and grown in 2% (fermentative conditions) or in 0.1% glucose (oxidative conditions) accumulated two types of 5-fluoro-UDP-sugars (FUDP-sugars): FUDP-N-acetylglucosamine and FUDP-glucose. No difference was observed in both conditions of culture. The viability of yeast cells on treatment with 5-fluorouracil was also followed. Both FUDP-sugars were partially purified by column chromatography (on Hypersil ODS and Mono Q columns) and characterized by: (i) treatment with alkaline phosphatase (EC 3.1.3.1), snake venom phosphodiesterase (EC 3.1.4.1) and UDP-glucose dehydrogenase (EC 1.1.1.22); (ii) UV spectra; and (iii) matrix-assisted laser desorption/ionization-time of flight mass analysis and 1H-nuclear magnetic resonance spectrometry. The syntheses of both FUDP-sugars were inversely related to the concentration of uracil and directly related to the concentration of 5-fluorouracil in the culture medium. The strain W303-1A, requiring uracil for growth, was useful as a tool to analyze the effect of 5-fluorouracil on nucleotide metabolism.
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PMID:Synthesis of FUDP-N-acetylglucosamine and FUDP-glucose in Saccharomyces cerevisiae cells treated with 5-fluorouracil. 1799 57


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