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:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of ornithine decarboxylase [EC 4.1.1.17] (ODC) in mouse L cells by components of the culture medium was investigated. It was found that further addition of amino acid mixture, but not of calf serum, to confluent cells of 5 day culture induced ODC and that this induction was accelerated by actinactinomycin D. In salt solution, addition of either amino acids or serum alone did not cause full induction, but addition of both together did. This induction, in contrast, was inhibited by actinomycin D. Induction by insulin, but not by cyclic AMP, was enhanced by a higher concentration of amino acids. These results can be explained by supposing that in non-growing cells there is stable RNA which is involved in ODC induction, possibly mRNA of ODC, and that the observed induction is caused by inhibition of enzyme degradation and accelerated translation, while in growing cells this RNA is unstable and ODC induction is controlled at the level of transcription.
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PMID:Induction of ornithine decarboxylase in cultured mouse L cells. II. Effects of additions of amino acids and serum. 19 44

Two effectors of ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17) have been extracted from an ODC- (speC-) mutant, Escherichia coli MA 255. One of these is an ODC inhibitor (Mr 15,000 +/- 2000) that is labile to trypsin; its activity increases 20-fold in response to increased polyamine levels in the growth medium. It has additional characteristics similar to those of the ODC antizyme of eukaryote cells: it is a noncompetitive inhibitor of ODC; the complex formed between ODC and the ODC inhibitor can be dissociated with salt to provide active ODC and active ODC inhibitor; furthermore, this E. coli ODC inhibitor is inhibitory to eukaryote ODC. A thermostable nondialyzable factor that activates ODC in vitro has also been extracted from MA255; increased polyamine levels in the growth medium caused a 1.6-fold increase in the activity of this ODC activator. Effectors with comparable activities have also been identified in the parent ODC+ (speC+) strain MA197. The fluctuations of the intracellular levels of these two ODC effectors during the growth of E. coli MA255 have been related to the temporal changes of the activity of ODC in the parent ODC+ MA197 strain. The mode of interaction of these three macromolecules, as reflected in the changes of the activity of ODC, appears to be complex. The results suggest that ODC activity may be controlled post-translationally by macromolecules that act as positive and negative effectors and whose levels fluctuate in response to the concentration of the end products of the reaction.
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PMID:Modulation of ornithine decarboxylase activity in Escherichia coli by positive and negative effectors. 36 95

(+/-)-2,5-Diamino-2-)cyanomethyl)pentanoic acid was obtained by the reaction of chloracetonitrile with the anion obtained by treatment of 3-(benzylideneamino)-2-piperidinone with sodium hydride, followed by hydrolysis in the presence of trifluoroacetic anhydride. The target compound was isolated as the monohydrochloride salt of the lactam. The compound was synthesized as a potential irreversible inhibitor of the enzyme L-ornithine decarboxylase by the mechanism generally known as suicide or Kcat inhibition. The synthesized compound produced no inhibition of the enzyme ornithine decarboxylase obtained from rat prostate gland. The inactivity of the target compound is attributed to the hydrophilicity of the cyanomethyl group.
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PMID:Inhibitors of polyamine biosynthesis VI: 2,5-Diamino-2-(cyanomethyl) pentanoic acid, a potential irreversible inhibitor of ornithine decarboxylase. 67 Dec 62

The enzyme ornithine decarboxylase (L-Ornithine carboxy-lyase, EC 4.1.1.17), has been partially purified from the livers of mice subjected to partial hepatectomy (6-8 h previously). Mouse liver ornithine decarboxylase requires pyridoxal phosphate, and dithiothreitol for maximal activity. The enzyme has a pH optimum of 7.3, it is inhibited in the presence of 0.3 M phosphate, glycine, Tricine and Tris. It shows no dependence on metal ions and is inhibited by high salt concentrations, particularly ammonium salts. The kinetics of the enzyme have been studied with putrescine (and analogs), spermidine and spermine, in the presence of both high and low levels of pyridoxal phosphate. High concentrations of pyridoxal phosphate inhibit the enzyme. The enzyme is also inhibited by low concentrations of putrescine (1 mM). As the concentration of putrescine increased to 10 mM, non-competitive inhibition was observed, this could be reversed by addition of higher levels of pyridoxal phosphate. Spermidine and spermine inhibit (noncompetitively) only at high concentrations (10 mM). Ornithine inhibits at high concentrations (2 mM). Spectral studies have shown that the observed kinetics of competitive inhibition at low concentrations of polyamine changing to noncompetitive inhibition at high polyamine concentrations are due to competition between enzyme and substrate (or inhibitor) for free (non-enzyme bound) pyridoxal phosphate. Noncompetitive inhibition arises through the formation of transient Schiff base complexes between amines and free pyridoxal phosphate. It also appears that the binding of substrate to the active site takes place through Schiff base formation with enzyme bound pyridoxal phosphate.
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PMID:The regulation of mouse liver ornithine decarboxylase by metabolites. 95 46

The activity of ornithine decarboxylase (ODC) in H-35 hepatoma cells depleted of Ca2+ by washing with 2 mM EGTA increased 35-fold after incubating for 4 h in a simple salt-glucose solution containing 10 mM L-asparagine and only if Ca2+ was replenished. Actinomycin D (5 micrograms/ml) and cycloheximide (20 microM) reduced the stimulatory effect by 84 and 100% respectively. Increase of active enzyme protein was also demonstrated by a 3-fold increase in alpha-difluoromethylornithine binding. Asparagine prolonged the half-life of induced ODC by 20% whereas Ca2+ reduced it by 32%. The observed inductive effects are not accounted for entirely by a direct influence of Ca2+ and asparagine on the turnover of ODC protein. These factors are likely to be parts of a signalling pathway leading to amplification of cellular ODC.
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PMID:Relationship between Ca2+ and L-asparagine in the induction of ornithine decarboxylase in H-35 rat hepatoma cells. 144 90

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

This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing alpha-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. alpha-difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by alpha-difluoromethylornithine treatment. These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic alpha-difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension.
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PMID:Polyamines, vascular smooth muscle, and deoxycorticosterone acetate-salt hypertension. 186 Jul 16

Asparagine stimulated the translation of ornithine decarboxylase (ODC) mRNA more than 10-fold in cultured hepatocytes which had been pretreated with glucagon in simple salt/glucose medium. Putrescine suppressed the increase in the rate of ODC synthesis caused by asparagine without significant change in the amount of ODC mRNA, suggesting that putrescine inhibited the effect of asparagine at least in part at the level of translation. Polysomal distribution of ODC mRNA was analyzed to examine the site of translational regulation by these effectors. In uninduced hepatocytes, most of the ODC mRNA was sedimented slightly after the 40 S ribosomal subunit. This ODC mRNA was sequestered from translational machinery since it was not shifted to the polysome fraction when peptide elongation was specifically inhibited by a low concentration of cycloheximide. In asparagine-treated cells, 40% of total ODC mRNA was in the polysomal fraction and formed heavier polysomes, indicating that asparagine stimulated both recruitment of ODC mRNA from the untranslatable pool and the initiation steps of translation. Putrescine did not change the distribution pattern of ODC mRNA on polysomes significantly. Thus, 30% of ODC mRNA remained on polysomes even when ODC synthesis was completely inhibited by putrescine. Paradoxically more than 70% of ODC mRNA was shifted into polysomes by putrescine in the presence of low concentrations of cycloheximide. These results, together with changes in the polysome profile, suggested that putrescine nonspecifically stimulated the recruitment of ODC mRNA from the untranslatable pool, whereas it specifically inhibited its translation at both the initiation and the elongation steps.
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PMID:Translational control mechanism of ornithine decarboxylase by asparagine and putrescine in primary cultured hepatocytes. 195 37

Previous studies from our own and other laboratories have shown that hypertension induces changes in the growth of arterial smooth muscle cells (SMC). The purpose of this study was to examine the role of ornithine decarboxylase (OrnDCase) in this process. OrnDCase, the rate limiting enzyme in polyamine biosynthesis, increases in activity early in the cell cycle, and has been used as a marker of cell growth or proliferation. Deoxycorticosterone (DOC)/salt hypertension was induced in male Wistar rats. At 1-3 day intervals of DOC/salt treatment, the aortas were removed and OrnDCase activity and DNA content were determined. The results indicated that OrnDCase activity increased as early as day 2 of DOC/salt administration, reached a peak at day 10, and fell to a baseline by day 16. DNA content increased after day 10 to levels approximately 25% greater than in controls. Significant increases in blood pressure were not observed until after day 8. The findings indicate that OrnDCase activity is stimulated by DOC/salt even before the rise in blood pressure and that factors other than blood pressure per se may be important in stimulating aortic smooth muscle cell growth in the development of hypertension.
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PMID:Aortic ornithine decarboxylase activity in deoxycorticosterone/salt hypertensive rats. 199 88

Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7-Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents.
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PMID:Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase. 211 May 12


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