Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible regulatory interactions of purified ornithine decarboxylase with DNA-directed RNA polymerases in isolated macronuclei from the ciliated protozoan Tetrahymena thermophila were studied. It has been found that highly purified ODC (specific activity 10.2 mumols CO2 x h-1 x mg-1), even at activities of 37,500 nmol CO2 x h-1 per ml failed to alter RNA polymerase activity in the in vitro transcription assay in the presence or absence of the substrate L-ornithine at 20mM. The naturally occurring di- and polyamines putrescine, spermidine, and spermine stimulated in-vitro-transcription in isolated macronuclei more at optimal Mg2+/Mn(2+)-concentrations than at suboptimal concentrations, suggesting that polyamines act via a mechanism which is distinct from that of the inorganic cations. Of the monovalent amine compounds tested, (NH4)+ at high concentrations between 40 and 50mM slightly stimulated activity whereas the onset of stimulation by the organic amine compounds, piperidine and cyclohexylamine, was inversely related to the hydrophobicity of each particular compound. In the series of divalent amines, the correct distance between the N-atoms appeared to be very important since ethylenediamine and piperazine did not stimulate significantly but did inhibit at concentrations above 5 mM. 1,3-Diaminopropane stimulated slightly but inhibited above 10 mM, whereas the 1,4-diamino compounds putrescine and 1,4-diaminocyclohexane (DAC) were equally potent stimulators with the more hydrophobic one, DAC, reaching the maximum at lower concentrations than putrescine. For the trivalent amines, the influence of correct spacing seems not to be as important: N-(2-aminoethyl)piperazine stimulated very similar to spermidine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of DNA-directed RNA polymerases in isolated macronuclei of the ciliated protozoan Tetrahymena thermophila. Effects of purified ornithine decarboxylase and amine compounds. 153 93

We have developed a clonal variant, named DF-40, from the N2a mouse neuroblastoma cell line, which has the ornithine decarboxylase (L-ornithine carboxylase, EC 4.1.1.17, ODC) gene amplified. When DF-40 cells were maintained in a simple salt glucose medium (e.g. Earle's blanced salt solution), L-asparagine alone was sufficient to induce a maximal increase in ODC activity. The increase in ODC activity correlated well with an increase in the amount of ODC protein. Northern blot analysis indicated that asparagine caused a 12-15-fold increase in ODC mRNA. The half-life of ODC mRNA induced by asparagine in DF-40 cells changed from more than 8 h to about 25 min upon removal of asparagine from the culture in the presence of actinomycin D. In contrast, asparagine had little or no effect on the rate of transcription of the ODC gene. Pulse labeling of cells for 15 min with [35S]methionine showed a 90-140-fold increase in the synthesis of ODC protein after 4-8 h of incubation with asparagine. The removal of asparagine from the medium resulted in a rapid loss of ODC protein with a half-life as short as 12 min. The presence of asparagine increased the half-life of ODC protein by 3-5-fold when measured in the presence of cycloheximide. Taken together, our data show that asparagine induced ODC gene expression in DF-40 cells, primarily by post-transcriptional stabilization of ODC mRNA. In addition, asparagine specifically stimulated the synthesis and suppressed the degradation of ODC protein.
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PMID:Mechanism of regulation of ornithine decarboxylase gene expression by asparagine in a variant mouse neuroblastoma cell line. 155 4

Lysine decarboxylase of Escherichia coli has been the subject of enzymological studies, and the gene encoding lysine decarboxylase (cadA) and a regulatory gene (cadR) have been mapped. This enzyme is induced at low pH in the presence of lysine and achieves maximal level under anaerobic conditions. The induction of lysine decarboxylase increases the pH of the extracellular medium and provides a distinctive marker in tests of clinical strains. We report the sequence of the cad operon encoding lysine decarboxylase, a protein of 715 amino acids, and another protein, CadB, of 444 amino acids. The amino acid sequence of lysine decarboxylase showed high homology to that of the lysine decarboxylase of Hafnia alvei with less homology to the sequence of speC, which encodes the biosynthetic ornithine decarboxylase of E. coli. The cadA and cadB genes were separately cloned and placed under the control of lac and tac promoters, respectively, to facilitate independent study of their physiological effects. The cadB gene product had a mobility characteristic of a smaller protein on protein gels, analogous to that found for some other membrane proteins. The CadB sequence showed homology to that of ArcD of Pseudomonas aeruginosa, encoding an arginine/ornithine antiporter. Excretion studies of various strains, the coinduction of cadB and cadA, and the attractive physiological role for an antiport system led to a model for the coupled action of cadA and cadB in uptake of lysine, the reduction of H+ concentration, and excretion of cadaverine.
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PMID:Nucleotide sequence of the Escherichia coli cad operon: a system for neutralization of low extracellular pH. 155 85

The purpose of this study was to elucidate the mechanism by which thyroid hormone alters urea synthesis. A set of three experiments was investigated in three groups of rats given 6-propyl-2-thiouracil (a thyroid inhibitor) without triiodothyronine treatment, treated with 6-propyl-2-thiouracil plus triiodothyronine or neither 6-propyl-2-thiouracil nor triiodothyronine (control). We attempted to determine whether the concentration of ornithine and N-acetylglutamate regulated urea synthesis and whether activities of two ornithine-catabolizing enzymes accounted for changes in ornithine concentration. Urinary excretion of urea and the liver concentration of N-acetylglutamate and ornithine in rats given 6-propyl-2-thiouracil plus triiodothyronine were significantly lower than in rats given 6-propyl-2-thiouracil alone. The liver concentration of N-acetylglutamate was correlated to urea excretion (r = 0.911, P less than 0.001). The activities of carbamylphosphate, synthetase, ornithine aminotransferase and ornithine decarboxylase in liver of the group treated with 6-propyl-2-thiouracil alone were significantly lower than those of the 6-propyl-2-thiouracil plus triiodothyronine-treated group. The results suggest that a higher liver concentration of N-acetylglutamate and ornithine in the hypothyroid (6-propyl-2-thiouracil only) rats is likely to stimulate urea synthesis. The thyroid hormone-induced increase in activities of ornithine catabolizing enzymes may be primarily responsible for changes in ornithine concentration.
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PMID:Changes in liver concentration of N-acetylglutamate and ornithine are involved in regulating urea synthesis in rats treated with thyroid hormone. 156 67

Ornithine decarboxylase (ODC) from Trichomonas vaginalis was inhibited irreversibly by several substrate analogs. Of these, DL-alpha-monofluoromethyldehydroornithine (MFMDO) and DL-alpha-monofluoromethylornithine (MFMO) were the most potent. The enzyme was unaffected by putrescine analogs suggesting that differences exist between the regulation of the trichomonad enzyme and that in other eukaryotes. In culture the ornithine analogs strongly inhibited putrescine synthesis and increased the generation time after 24 hr of exposure. In a semi-defined growth medium MFMDO methyl and ethyl esters increased the generation time from 4.5 hr to 9.0 and 8.2 hr, respectively. In standard undefined growth medium the trichomonad ODC was fully induced only after 15 hr (late log) and had an extended half-life of greater than 8 hr.
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PMID:Inhibition of Trichomonas vaginalis ornithine decarboxylase by amino acid analogs. 164 39

The polyamines spermidine and spermine are essential for cell proliferation. Most growth factors stimulate polyamine synthesis by inducing ornithine decarboxylase activity, which catalyzes the formation of putrescine from ornithine. Putrescine can then be utilized either for polyamine biosynthesis or may serve as a substrate for diamine oxidase (DAO), leading to formation of gamma-aminobutyric acid (GABA). Growth of the oxyntic mucosa of the stomach is stimulated by feeding, by trophic hormones such as gastrin and by exogenous administration of putrescine. Conversely, fasting, as well as ornithine decarboxylase inhibition decrease oxyntic mucosal DNA synthesis. We now demonstrate that fasted rats show a high degree of [3H]GABA formation from [3H]putrescine in the oxyntic mucosa and that feeding or injections of gastrin, caerulein or the DAO-inhibitor aminoguanidine decrease such [3H]GABA formation and, instead, stimulate formation of [3H]spermidine. Moreover, gastrin injections reduced oxyntic mucosal DAO activity. Thus, oxyntic mucosal DAO activity is regulated by tropic factors and may be involved in growth regulation by controlling intramucosal putrescine metabolism.
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PMID:Regulation of gastric mucosal diamine oxidase activity by gastrin. 164 66

Differentiation of mouse neuroblastoma cells has been shown to be accompanied by changes in polyamine metabolism and a decrease in polyamine content. We have previously shown that alpha-difluoromethyl ornithine, a suicide inhibitor of ornithine decarboxylase (ODC, EC 4.1.1.17) and suboptimal concentrations of dibutyryl cAMP (0.1 to 0.2 mM) are effective in inducing the differentiation of mouse Neuro-2a (N2a) neuroblastoma cells. Exogenously added putrescine or spermidine can block the action of DFMO and dibutyryl cAMP, suggesting that polyamines may play a regulatory role in neuroblastoma differentiation. We have now isolated from N2a cells a clonal variant line, DF-40, whose ODC gene has been amplified by 40-fold. The DF-40 cells overproduced the ODC enzyme and contained very high levels of putrescine, spermidine and spermine. Treatment of DF-40 cells with dibutyryl cAMP or DFMO/dibutyryl cAMP led to a more than 80% reduction in polyamine content. Such a decrease did not cause the DF-40 cells to differentiate. Polyamine content in the treated DF-40 cells was still comparable or higher than that in the undifferentiated N2a cells. In contrast, serum-deprivation induced full differentiation of DF-40 cells. Levels of polyamine in the differentiated DF-40 cells, however, were also found to be comparable to that in the undifferentiated N2a cells. Exogenously added polyamines could not block the differentiation of DF-40 cells induced by serum-deprivation, suggesting that the action of polyamines in regulating neuroblastoma differentiation may depend on the presence of serum factors.
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PMID:Differentiation of a mouse neuroblastoma variant cell line whose ornithine decarboxylase gene has been amplified. 166 Nov 61

We reported recently that administration of ([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC; EC 4.1.1.50), a key enzyme in the synthesis of spermidine, cures African trypanosome infections in mice. The precise mechanism of action of MDL 73811 was not clear because a rapid disappearance of trypanosomes from the bloodstream of treated rats occurred before significant depletion of spermidine. Administration of MDL 73811 to Trypanosoma brucei brucei-infected rats resulted in a 70% decrease in parasitaemia within 1 h and a complete disappearance of parasites by 5 h. The reduction in parasitaemia was accompanied by complete inhibition of AdoMetDC activity by 10 min after injection of MDL 73811; inhibition was sustained for at least 4 h. Polyamine levels in trypanosomes were unaffected during the first 1 h in which the marked decrease in parasitaemia was observed, but parasite AdoMet levels increased 20-fold within this time. In contrast, exposure of cultured mammalian cells to MDL 73811 resulted in only a 1.5-2-fold increase in AdoMet levels over a 6 h time course. Experiments with inhibitors of ornithine decarboxylase (ODC) also suggested that the increased AdoMet levels might be an important factor for antitrypanosomal efficacy. Trypanosomes taken from rats treated for 36 h with eflornithine, an inhibitor of ODC, were depleted of putrescine and had markedly decreased spermidine levels. These organisms also had less than 10% of control AdoMetDC activity, and had elevated decarboxy AdoMet (greater than 4000-fold) and AdoMet (up to 50-fold) levels. The methyl ester of alpha-monofluromethyl-3,4-dehydro-ornithine (delta-MFMO-CH3), which cures murine T. b. brucei infections, and the ethyl ester analogue of this compound (delta-MFMO-C2H5), which does not cure this infection, become ODC inhibitors upon hydrolysis and thus were tested for their effects on trypanosomal polyamines, AdoMet and decarboxy AdoMet levels. Although both esters of delta-MFMO depleted trypanosomal polyamines, AdoMet and decarboxy AdoMet levels were elevated in T. b. brucei from infected mice treated with delta-MFMO-CH3 but not in parasites from mice treated with the delta-MFMO-C2H5. These data suggest that inhibition of AdoMetDC, either directly with MDL 73811 or indirectly with inhibitors of ODC, apparently leads to a trypanosome-specific elevation of AdoMet. It is possible that major changes in AdoMet, rather than changes in polyamines, may be responsible for the antitrypanosomal effects of these drugs.
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PMID:Antitrypanosomal effects of polyamine biosynthesis inhibitors correlate with increases in Trypanosoma brucei brucei S-adenosyl-L-methionine. 167

This study was designed to determine the distribution of immunoreactive epidermal growth factor (EGF) in the gastrointestinal tract and the action of this peptide on pancreatic secretion in vivo and in vitro. Immunoreactive EGF was found in large amounts in the salivary glands and the pancreas and in the pancreatic juice. EGF infused subcutaneously (50 micrograms/kg-h) in conscious rats with intact or removed salivary glands stimulated pancreatic protein secretion after 4 h of peptide infusion; this effect was completely prevented by the pretreatment with DL-difluoromethyl-ornithine (DFMO) (200 mg/kg), an irreversible inhibitor of activity of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis. EGF added to the incubation medium in concentrations ranging from 10(-10)-10(-6) M increased, in a concentration-dependent manner both unstimulated and stimulated by caeruelin or urecholine, amylase release from dispersed pancreatic acini obtained from rats pretreated in 3 h with EGF in a dose of 50 micrograms/kg-h. Spermine given at concentrations ranging from 10(-12)-10(-6) M to the freshly prepared rat pancreatic acini also increased amylase release in a concentration-related manner. DFMO injected in a single dose (200 mg/kg), before the infusion of EGF to the rats, completely abolished the stimulatory effect of EGF on amylase release, but failed to affect that of spermine. This study shows that 1. EGF is present in large amounts in pancreatic tissue and pancreatic juice. 2. EGF stimulates pancreatic secretion in vivo and amylase release in vitro from isolated rat pancreatic acini. 3. The activation of ODC and polyamine biosynthesis in acinar cells plays an important role in EGF-induced stimulation of pancreatic secretion.
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PMID:Distribution, release, and secretory activity of epidermal growth factor in the pancreas. 169 82

Administration of thyroxine to rat pups leads to precocious development of the pancreas. The role of ornithine decarboxylase (ODC) and polyamines in thyroxine-induced pancreatic maturation was examined. Rat pups (aged 5 days) were given daily subcutaneous injection of thyroxine (0.1 micrograms/g body wt.) until the day before death. Serial ODC activities were measured in pancreatic homogenates after 1, 2, 3, 4, 5, 6, 7 and 10 days of thyroxine treatment. There was a biphasic induction of ODC activities by thyroxine: an early peak appeared on day 2 of treatment followed by a decrease on day 4; a second peak was evident on day 5 and then a decrease to control values by day 7. Significant increases in tissue concentrations of putrescine and spermidine were observed concomitant with two peaks of ODC activity. Pancreatic amylase concentration, DNA and protein also showed a significant increase after thyroxine treatment. Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, given orally (8% in drinking water) to nursing dams at postnatal day 5 for 5 days caused an 83% inhibition of pancreatic ODC activity in thyroxine-treated pups when compared to thyroxine-treated pups not exposed to DFMO. Concomitantly, the thyroxine-induced increases in pancreatic weight, protein and amylase activity were suppressed. Our results suggest that increases in ODC activities and polyamine levels are critical intermediary steps in the precocious induction of pancreatic development by thyroxine.
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PMID:Essential role for polyamine biosynthesis in thyroxine stimulated pancreatic development in neonatal rats. 171 Sep 34


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