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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Digestion of tRNA by electrophoretically pure phosphodiesterase is limited to a short sequence of nucleotides at the 3'-terminus. On the average, four percent of all nucleotides can be released from tRNA. The optimum Mg2 concentration is 10mM and the optimum pH 9.2. The mode of action is a random attack by the enzyme on the substrate. The terminal AMP is completely removed at 15 degrees C after short incubation; about 400 mol of AMP were removed per min by 1 mol of enzyme. The following CMP residues are released much more slowly; at 15 degrees C incompletely, and at 37 degrees C more or less completely in 1 h. In about 50% of the tRNA molecules, the fourth nucleotide could be removed in very long incubations or with very high enzyme concentrations.
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PMID:Limited hydrolysis of tRNA by phosphodiesterase. 0 Feb 96

The effects of various agents on the newly identified cyclic CMP phosphodiesterase (C-PDE) in crude extracts of a number of rat tissues and on the enzyme partially purified from the rat liver were examined. Papaverine and 1-methyl-3-isobutylxanthine were without effects on C-PDE at concentrations that inhibited up to 90% of cyclic AMP phosphodiesterase (A-PDE) and cyclic GMP phosphodiesterase (G-PDE) activities. When assayed using 1 micron substrates, theophylline inhibited C-PDE to a lesser extent than A-PDE and G-PDE. 2'-Deoxy cyclic AMP (specific A-PDE inhibitor) and 2'-deoxy cyclic GMP (specific G-PDE inhibitor) were relatively poor and non-specific inhibitors for C-PDE. Imidazole, while augmenting the high Km A-PDE and G-PDE from the liver but not from the heart, was without effect on the liver C-PDE but stimulated the heart C-PDE. Potassium phosphate was more specific in inhibiting C-PDE than A-PDE and G-PDE. The present findings suggest that C-PDE represents a potential site of specific pharmacological regulations, and that C-PDE may be a separate enzyme distinguishable from the purine cyclic nucleotide class of phosphodiesterases.
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PMID:Effects of phosphodiesterase inhibitors, imidazole and phosphate on cyclic CMP phosphodiesterase are different from those on cyclic AMP and cyclic GMP phosphodiesterases. 8 41

Two of the new anticancer drugs recently synthesized in our laboratory from conjugation of ara-C2 and several corticosteroids linked through a phosphodiester bond include prednisolone- (I) and prednisone-p-ara-C (II). They were demonstrated to be enzymatically hydrolyzed to the corresponding steroid and ara-CMP and the latter was further shown to be hydrolyzed to ara-C by phosphodiesterase I, snake venom, 5'-nucleotidase, and acid phosphatase. However, the conjugates were shown to be resistant to hydrolysis by alkaline phosphatase. The activity of conjugates I and II against L1210 lymphoid leukemia in female mice (C3D2F1/J) was significantly greater than that of ara-C alone or in combination with the steroid. In fact, when the optimum dosage of 75 (mumol/kg)/day x 5 was used, the administration of ara-C alone was followed by an increased life span (ILS) of 45%. This result is similar to that previously reported. With the same equimolar doses of mixtures of ara-C and either prednisolone or prednisone, the ILS values were 40 and 44%, respectively. However, when the conjugates were used, the ILS values were 89 and 100% respectively. These findings seem promising and have provided the bases for continued study of these new compounds.
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PMID:Nucleoside conjugates as potential antitumor agents. 2. Synthesis and biological activity of 1-(beta-D-arabinofuranosyl)cytosine conjugates of prednisolone and prednisone. 11 58

A phosphodiesterase activity that preferentially hydrolyzed cytidine 3':5'-monophosphate was partially purified from rat liver extract. The enzyme was best activated by Fe2+ (5 to 10 mM). Mn2+ and Mg2+ were less effective, whereas Zn2+, Co2+, and Ca2+ were ineffective. It exhibited kinetics typical of a high Km phosphodiesterase, with a Km for cycli CMP of 2.4 mM. The enzyme, inhibited by theophylline and 1-methyl-3-isobutyl xanthine to much less extents than cyclic AMP and cyclic GMP phosphodiesterases, was found in all rat tissues examined, with highest levels seen in the liver, kidney, and intestine, and lowest levels found in the skeletal muscle, cerebellum, aorta, and blood cells. The enzyme levels in the regenerating liver were found to be about 40% lower than the control liver of rats; they were also 3 to 10 times lower in the fetal liver, lung, and heart than the corresponding adult tissues of guinea pigs. These findings suggest that depressed cyclic CMP phosphodiesterase may be in part related to cell proliferation, in line with reports that the regenerating liver has higher levels of cyclic CMP (Bloch, A. (1975) Adv. Cycli Nucleotide Res. 5, 331-338) and cytidylate cyclase (Cech, S. Y., and Ignarro, L.J. (1977) Science 198, 1063-1065).
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PMID:Cytidine 3':5'-monophosphate phosphodiesterase in mammalian tissues. Occurrence and biological involvement. 20 53

A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.
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PMID:Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver. 21 May 3

Changes in levels of the newly discovered cytidine 3':5'-cyclic monophosphate (cyclic CMP) phosphodiesterase in some representative tissues (cerebral cortex, kidney, intestine, liver, heart, and lung) of guinea pigs from various developmental stages (fetus, neonate, pup, and adult) were studied and compared with those of cyclic AMP and cyclic GMP phosphodiesterases in the same tissues. It was observed that the tissue levels of cyclic CMP phosphodiesterase were invariably the lowest in every one of the fetal tissues examined, the highest in the corresponding tissues from the pups and adult, with intermediate levels seen in some neonatal tissues. The patterns of the ontogenetic changes in levels of cyclic AMP and cyclic GMP phosphodiesterase activities, however, were variable and tissue specific. These findings suggest that the depressed cyclic CMP phosphodiesterase activity (hence, the elevated cyclic CMP concentration) is perhaps a common factor in developing tissues undergoing rapid cell proliferation. The data also suggest that metabolism of cyclic CMP is perhaps more closely related to cell proliferation than the metabolism of cyclic AMP or cyclic GMP.
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PMID:Depression of cytidine 3':5'-cyclic monophosphate phosphodiesterase activity in developing tissues of guinea pigs. 21 50

A rapid, simple, and direct assay for 3',5'-cyclic nucleotide phospho-diesterase activity is based on the effective separation of cyclic AMP, cyclic GMP or cyclic CMP from their corresponding 5'-nucleotides and nucleosides by chromatography on a polyacrylamide-boronate gel. The affinity of the boronate residue for cis-diols results in the retention of 5'nucleotides and nucleosides while 3',5'-cyclic nucleotides are not retained. The coelution of all 5'-nucleotides and nucleosides allows for the accurate assessment of phosphodiesterase activity in preparations contaminated by other purine metabolizing enzymes such as 5'-nucleotidases and nucleotide and nucleoside deaminases. Phosphodiesterase activity assayed by this means yields linear reaction kinetics with respect to time and amount of enzyme protein. Low blank values obtained allow for detection of as little as 2-3% conversion of substrate to product.
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PMID:A simple direct assay of 3',5'-cyclic nucleotide phosphodiesterase activity based on the use of polyacrylamide-bononate affinity gel chromatography. 22 Feb 90

The hypothesis that the small portion of cellular phosphoinositide participating in signal transduction might be preferentially recycled within the plasma membrane was tested in rat glioma (C6) and murine neuroblastoma (N1E-115) cells. Percoll density gradient centrifugation was used to isolate a purified plasma membrane fraction and the subcellular distribution of all enzymes mediating phosphoinositide turnover was assessed. A small but significant proportion of PtdInsP2-specific phosphodiesterase was located in the plasma membrane but only two of the five enzymes required to replace PtdInsP2 (diacylglycerol kinase and PtdInsP kinase) also were present. CTP:phosphatidate cytidylyltransferase and CMP-phosphatidate:inositol phosphatidyltransferase were located exclusively in a microsomal fraction containing enriched levels of endoplasmic reticulum markers. Thus, diacylglycerol from agonist-stimulated cleavage of PtdInsP2, or phosphatidic acid formed from it, must be transferred to the endoplasmic reticulum for conversion to PtdIns. Plasma membrane also lacked PtdIns kinase. If the soluble PtdIns kinase has access to membrane-bound substrate, PtdIns may be phosphorylated to PtdInsP before or during transport to the plasma membrane. Phosphorylation by the predominantly plasma membrane PtdInsP kinase to form PtdInsP2 completes the cycle. PtdInsP phosphatase was present in all membrane fractions suggesting that PtdInsP can be returned to the PtdIns pool in plasma membrane and elsewhere. PtdInsP2 phosphatase was almost exclusively in the cytosol suggesting that reversible interchange between PtdInsP and PtdInsP2 in the plasma membrane may be modulated by the ability of this phosphatase to act on PtdInsP2 in the membrane. Thus, PtdIns resynthesis in the plasma membrane of these cells does not occur and is not required for phosphoinositide-mediated signal transduction.
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PMID:Phosphoinositide metabolism in cultured glioma and neuroblastoma cells: subcellular distribution of enzymes indicate incomplete turnover at the plasma membrane. 215 58

Cyclic CMP phosphodiesterase activity was demonstrated in rat liver, heart, brain, kidney, intestine, skeletal muscle, blood, testes, ovaries, spleen and lung; that present in the liver was purified to homogeneity by a sequential process of ammonium sulphate fractionation, gel filtration, two ion-exchange chromatographic steps, preparative electrophoresis and two affinity chromatographic stages with selection at each stage for maximum specificity. The final enzyme preparation was confirmed as a single protein by HPLC and isoelectric focussing; the total yield obtained was 1.5% and the final specific activity of 48.6 mumol cyclic CMP hydrolysed/min/mg reflected a 88,000 fold purification. The phosphodiesterase had a Mr of 2.8 X 10(4), pH optimum 7.2-7.4, isoelectric point between 4.2 and 4.4 and a Km of 9.0 mM cyclic CMP. This enzyme differs from a previously isolated cyclic CMP phosphodiesterase in its amino acid composition and specificity. The absolute specificity for 3',5'-cyclic CMP as substrate distinguishes this cyclic CMP phosphodiesterase from all other reported phosphodiesterases and shows it to be a novel enzyme. Its potential as a research tool and the significance of its occurrence are discussed.
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PMID:Cyclic CMP phosphodiesterase: isolation, specificity and kinetic properties. 301 81

1. An enzyme preparation from rat-liver microsomes incorporated all four ribonucleotides from the corresponding triphosphates into ribosomal RNA. The reaction was Mn(2+)-dependent, but UMP incorporation also occurred in the presence of Mg(2+). 2. The incorporation of any one ribonucleotide was inhibited by the presence of the other three ribonucleoside triphosphates and by denatured DNA. 3. The product of the reaction consisted of short chains of homopolymer attached to the primer ribosomal RNA. 4. ;Soluble' RNA, synthetic polyribonucleotides, and oligoribonucleotides were also effective primers for CMP incorporation. 5. When phosphodiesterase-treated ;soluble' RNA was the primer, CMP was incorporated into positions usually occupied by the normal terminal trinucleotide sequence of intact ;soluble' RNA, but the enzyme did not synthesize a specific terminal sequence consisting of a defined number of CMP residues.
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PMID:The incorporation of cytidine 5'-monophosphate and other ribonucleotides by an enzyme preparation from rat-liver microsomes. 429 58


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