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)

The effect of an analogue of cAMP on the uptake and metabolism of choline in the heart was studied in isolated cardiac cells. The cells were obtained from 7-day-old chick embryos and maintained in culture. The effects of cAMP were studied using the dibutyryl cAMP analogue and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. After a 2-h incubation with [3H]choline, about 85% of the label was recovered in phosphocholine, with most of the rest in phospholipid. During a subsequent chase incubation, [3H]phosphocholine was transferred to phosphatidylcholine with little accumulation in CDP-choline. This suggests the rate-limiting step for the conversion of phosphocholine to phosphatidylcholine in these cells is the synthesis of CDP-choline. cAMP decreased the incorporation of choline into phosphatidylcholine, but did not change the flux of metabolites through the step catalyzed by CTP:phosphocholine cytidylyltransferase. cAMP had little effect on choline uptake at low (1-25 microM) extracellular choline concentrations, but significantly (p less than 0.05) decreased choline uptake at higher (37.5-50 microM) extracellular choline concentrations. Thus, cardiac cells take up and metabolize choline to phosphocholine, with CTP:phosphocholine cytidylyltransferase being the rate-limiting step in phosphatidylcholine biosynthesis. cAMP decreases [3H]choline uptake and its subsequent incorporation into phosphocholine and phospholipid. However, the metabolism of choline within the cell is unaffected.
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PMID:Effect of cAMP on choline uptake and phosphatidylcholine biosynthesis in cultured chick heart cells. 283 58

The short- and long-term effects of cyclic AMP analogues and phosphodiesterase inhibitors on phosphatidylcholine biosynthesis in monolayer cultures of rat hepatocytes were investigated. All the compounds tested produced an inhibition of phosphatidylcholine biosynthesis for up to 6 h after addition to the hepatocyte medium. The reduced rate of lipid synthesis was a function of the concentration of cyclic AMP analogue and was independent of the concentration of choline in the medium. The proportion of choline oxidized to betaine was relatively unaffected. Choline was incorporated into hepatocytes by saturable and non-saturable mechanisms. Although the various cAMP analogues had different effects on choline uptake, chlorophenylthio-cAMP reduced uptake of choline by 28% for cells treated for 1.5-15 h. This analogue lowered the Vmax of the saturable component of choline transport by 3.6-fold. Prolonged incubation of the hepatocytes with cAMP analogues resulted in a reversal of the inhibition of phosphatidylcholine synthesis. After 15 h all the compounds tested stimulated the relative incorporation of [methyl-3H]choline into phosphatidylcholine. For hepatocytes incubated with chlorophenylthio-cAMP for 14-16 h, there was a 2.8-fold stimulation of the rate of phosphatidylcholine synthesis. The enzymes responsible for the conversion of choline into phosphatidylcholine were examined at various times after addition of the chlorophenylthio-cAMP to the hepatocyte medium. The reduced synthesis of phosphatidylcholine strongly correlated with inhibition of CTP:phosphocholine cytidylyltransferase activity. After 12 h of treatment with the analogue, the relative inhibition of the cytidylyltransferase activity was reversed.
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PMID:Prolonged effects of cyclic AMP analogues of phosphatidylcholine biosynthesis in cultured rat hepatocytes. 618 53

While steady-state kinetic parameters (metabolite pools, Km and activation energies) are partially known for the enzymes involved in phosphatidylcholine synthesis and degradation in mammalian brain, they are not available for the nervous system of lower vertebrates or invertebrates. Since the extent of evolutionary development of an enzyme is not known a priori, we evaluated the kinetic and thermodynamic parameters of choline kinase, CTP:phosphocholine cytidylyltransferase, choline phosphotransferase and glycerophosphorylcholine phosphodiesterase in squid (Loligo pealei) optic lobe, dogfish (Mustelus canis) and rat brain. For all these enzyme activities, basic similarities in Km and inhibitor effect were found. The same was true for the activation energies Ea, with the exception of squid choline kinase and dogfish cytidylyltransferase. Treatment of microsomal membranes with phospholipase C sharply inhibited cytidylyltransferase activity in all three animal species. In dogfish brain, glycerophosphorylcholine phosphodiesterase activity was undetectable. Our results are consistent with the notion that the kinetic properties of the enzyme activities leading to the preservation of the phosphatidylcholine membranous pool may have appeared early in metazoan evolution and been fully conserved in mammals.
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PMID:Evolutionary comparison of enzyme activities of phosphatidylcholine metabolism in the nervous system of an invertebrate (Loligo pealei), lower vertebrate (Mustelus canis) and the rat. 852 26