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

Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4).
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PMID:Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds. 0 56

1. A phosphodiesterase, active at an alkaline pH, is present in the outer cortex of rat kidney and hydrolyses glycerylphosphorylinositol into glycerol and phosphorylinositol. Some inositol cyclic phosphate can also be formed indicating that the enzyme can act as a cyclizing phosphotransferase. 2. The enzyme is stimulated by Ca2+(2-3mM) whereas Mg2+ is inhibitory. 3. The activity is markedly stimulated by low concentrations of thiol reagents (1-2mM) such as cysteine or dithiothreitol. 4. The properties of the enzyme have been compared with glycerylphosphinicocholine diesterase (EC 3.1.4.2), which is also present in the isolated enzyme complex, and it is concluded that the enzymes have separate identities.
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PMID:A phosphodiesterase in rat kidney cortex that hydrolyses glycerylphosphorylinositol. 19 16

Although GPC has long been recognized as a degradation product of phosphatidylcholine, only recently is there wide appreciation of its role as a compatible and counteracting osmolyte that protects cells from osmotic stress. GPC is osmotically regulated in renal cells. Its level varies directly with extracellular osmolality. Cells in the kidney medulla in vivo and in renal epithelial cell cultures (MDCK) accumulate large amounts of GPC when exposed to high concentrations of NaCl and urea. Osmotic regulation of GPC requires choline in the medium, presumably as a precursor for synthesis of GPC. Choline transport into the cells, however, is not osmoregulated. The purpose of the present studies was to use MDCK cell cultures as a defined model to distinguish whether osmotically induced accumulation of GPC results from increased GPC synthesis or decreased GPC disappearance. The rate of incorporation of 14C from [14C]choline into GPC, the steady-state GPC synthesis rate, and the activity of phospholipase A2 (which can catalyze a step in the synthesis of GPC from phosphatidylcholine) are not increased by high NaCl and urea. In fact all are decreased by approximately one-third. Therefore, we find no evidence that high NaCl and urea increases the GPC synthesis rate. On the other hand, the rate coefficient for cellular GPC disappearance and the activity of GPC:choline phosphodiesterase (EC 3.1.4.2), which catalyzes degradation of GPC, are decreased by approximately two-thirds by high NaCl and urea. We conclude that high NaCl and urea increase the level of GPC by inhibiting its enzymatic degradation.
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PMID:Accumulation of glycerophosphocholine (GPC) by renal cells: osmotic regulation of GPC:choline phosphodiesterase. 165 65

A high-performance liquid chromatographic method using an enzymic reactor for determination of L-alpha-glycerophosphorylcholine in pharmaceutical forms is described. The procedure includes incubation of L-alpha-glycerophosphorylcholine with glycerophosphorylcholine phosphodiesterase (EC 3.1.4.2), giving choline and glycerophosphate, and subsequent chromatography of choline with a post-column enzymic reactor and electrochemical detection. The results obtained show a close linearity of the whole assay from 2 to 150 nmol/ml L-alpha-glycerophosphorylcholine, the sensitivity being 2 pmol per 20 microliters of injected sample. The precision of the method in the analysis of L-alpha-glycerophosphorylcholine in pharmaceutical forms, ampoules and capsules, was 1.34 and 1.21%, respectively.
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PMID:High-performance liquid chromatographic assay of L-alpha-glycerophosphorylcholine using a two-step enzymic conversion. 165 23

Peri-tumoral injection of recombinant human interleukin-1 beta in mice transplanted s.c. with Friend erythroleukemia cells (FLC) resulted in marked inhibition of tumor growth and increased survival. However, in vitro treatment of FLC (745 or 3Cl-8) with IL-1 beta barely inhibited cell multiplication. IL-1 beta, injected into established solid tumors, induced marked morphologic changes. Vascular congestion and focal extravasation of erythrocytes were observed as early as 6 hr after injection with IL-1 beta of FLC and L1210 tumors and HeJ16 fibrosarcomas. Focal areas of disaggregation of tumor cells and tumor necrosis were observed 6 and 24 hr after IL-1 injection. These morphologic changes were similar to those observed in FLC tumors or HeJ16 fibrosarcomas treated with TNF-alpha or beta. These cytokines determined morphological changes in tumor blood vessels of FLC tumors within 1 hr of injection. Freshly dissected FLC tumors and their tissue extracts were studied by Nuclear Magnetic Resonance (NMR) spectroscopy, shortly after peri-tumoral injection of IL-1 beta or TNF-beta. After 6 hr, both cytokines induced a 3-fold reduction in the levels of two catabolites, glycerophosphorylcholine and glycerophosphorylethanolamine, an accumulation of sn-glycerol 3-phosphate and a more than 10-fold increase in the choline/phosphorylcholine ratio. These results are similar to those reported for TNF-alpha, and can be interpreted on the basis of an activation of glycerophosphorylcholine phosphodiesterase (EC 3.1.4.2) and partial inhibition of choline kinase (EC 2.7.1.32). IL-1 beta and TNF-beta (like TNF-alpha) also induced alkaline shifts (0.10-0.25 units) in the average intratumoral pH value. We suggest that alterations of tumor blood vessels may be the primary events in solid tumors treated with IL-1 beta or TNF. Such alterations lead to early changes in tumor metabolism and subsequent tumor cell degeneration.
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PMID:Interleukin-1 beta induces tumor necrosis and early morphologic and metabolic changes in transplantable mouse tumors. Similarities with the anti-tumor effects of tumor necrosis factor alpha or beta. 278 94

Experiments with glycerophosphocholine phosphodiesterase (GPC diesterase, EC 3.1.4.2.) in rat brain microsomes suggest that, although its activity is inhibited by low concentrations of calmidazolium, its dependence on Ca2+ ions is not modulated by calmodulin. The activity of glycerophosphocholine choline phosphodiesterase (choline phosphohydrolase, EC 3.1.4.38) was much lower than that of the GPC diesterase. A relatively inexpensive method for the preparation of sn-glycero-3-phospho [Me-14C]choline is described.
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PMID:The hydrolysis of glycerophosphocholine by rat brain microsomes: activation and inhibition. 303 33

The organic osmolyte, glycerophosphocholine (GPC), accumulates in renal cells in response to high concentrations of either NaCl or urea, despite the very different effects of these solutes on cell function and volume. Together, high levels of these solutes increase GPC amount in Madin-Darby canine kidney cells by inhibiting its enzymatic degradation. The present study tests the effects of NaCl and urea, individually, on GPC accumulation and its degradation. A technique was developed to determine the absolute rate of GPC degradation by measuring the initial rate of disappearance of [3H]GPC (pulsed into the cells by hypotonic shock) and the specific activity of GPC in the cells. The mass of GPC in the cells was measured by another newly developed method, a sensitive chemiluminescent assay. We find that exposure to high NaCl or urea decreases the absolute rate of cellular GPC degradation by approximately one-half during the first 20.5 h. Reductions in GPC degradation are accompanied by commensurate decreases in the activity of GPC:choline phosphodiesterase (GPC:PDE; EC 3.1.4.2), an enzyme that catalyzes degradation of GPC. Activity of GPC:PDE falls > 50% in cells exposed for 2 h to high osmolality. Inhibition is sustained for 7 days with high urea alone. In contrast, with high NaCl alone, GPC:PDE activity reverts to control values by 7 days, by which time synthesis of GPC is increased, accounting for sustained GPC accumulation. Collectively, these data suggest that GPC accumulation in response to either high NaCl or urea occurs initially by inhibition of its degradation but that the effect of NaCl on degradation differs, in that it is transient, while that of urea is sustained.
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PMID:Osmoregulation of GPC:choline phosphodiesterase in MDCK cells: different effects of urea and NaCl. 763 58

Enzymatic conversion of glycosylphosphatidylinositol (GPI)-linked Zn2+-glycerophosphocholine phosphodiesterase was investigated. The activity of glycosylphosphatidylinositol-specific phospholipase-D (GPI-PLD), based on the conversion of amphiphilic form of phosphodiesterase into hydrophilic form, showing an optimum pH of about pH 6.6, increased continuously until 60 min. The activity of membrane-bound GPI-PL, based on the formation of hydrophilic form of phosphodiesterase, exhibiting an optimum pH of 7.4, increased up to 30 min, and reached a plateau. Inhibition studies indicate that while GPI-PLD activity was generally sensitive to ionic bio-detergents, it was not inhibited by myristoyl glycerol, a neutral detergent. Meanwhile, the membrane-bound GPI-PL was not affected remarkably by these detergents except that myristoyl glycerol expressed a modest increase of activity of membrane bound GPI-PL. In addition, the membrane-bound GPI-PL appeared to be enhanced by by suramin or oleic acid, which strongly inhibited GPI-PLD. From this results, it is suggested that in brain there may be two phospholipases responsible for the conversion of membrane-bound GPI-anchors to hydrophilic forms, and that this conversion might be regulated by endogenous lipids.
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PMID:Enzymatic release of Zn2+-glycerophosphocholine cholinephosphodiesterase from brain membranes by glycosylphosphatidylinositol-specific phospholipases and its regulation. 957 79

In pericytes from bovine retina, the enzyme glycerophosphocholine phosphodiesterase, catalyzing the hydrolysis of sn-glycero-3-phosphocholine to glycero-3-phosphate and choline, has been characterized with respect to pH optimum, metal ion dependence, Km, inhibitors, and subcellular localization. In these cells, the natural substrate sn-glycero-3-phosphocholine was present at relatively high concentration (6.4 +/- 1.2 nmol/mg protein), and the EDTA-sensitive phosphodiesterase activity was also found to be markedly high (9.80 +/- 1.5 nmol/min/mg protein) compared to that estimated in liver and brain (1-3 nmol/min/mg protein) or in renal epithelial cell culture (0.27 nmol/min/mg protein). The reaction conditions were in general agreement with those found earlier in brain and other tissues. The majority of the enzyme specific activity was located in the plasma membrane, whereas a minor part was present in the microsomal fraction. The physiological significance of the high catabolic phosphodiesterase activity in these cells may be related to the transfer, followed by deacylation, of lysophosphatidylcholine from the bloodstream to nervous tissue. In addition, capillary pericytes in culture were able to incorporate 3H-choline rapidly into choline-containing soluble phosphorylated intermediates and into phosphatidylcholine. To find a positive and negative effector on phosphatidylcholine formation, adenosine, an important intercellular mediator in the retina in response to alterations in oxygen delivery, and endothelin-1, a potent paracrine mediator present at the blood-brain and blood-retina barrier, were tested. The cells cultured for 1 or 24 h in a medium containing adenosine at concentrations of 10(-6) and 10(-4) M showed significant reduction in 3H-choline incorporation compared to control cultures, whereas endothelin-1, at a concentration of 10 and 100 nM, caused stimulation of phosphatidylcholine biosynthesis. These findings provide evidence that both agonists may modulate phosphatidylcholine metabolism in pericytes.
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PMID:Characterization of glycerophosphocholine phosphodiesterase activity and phosphatidylcholine biosynthesis in cultured retinal microcapillary pericytes. Effect of adenosine and endothelin-1. 1266 19