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)

The importance of certain amino acid residues in mammalian ornithine decarboxylase activity and degradation was studied by site-specific mutagenesis. Changes were made to the mouse ornithine decarboxylase cDNA in a plasmid containing a T7 RNA polymerase promoter. The plasmid was then used for the synthesis of RNA, which was translated in a reticulocyte lysate system. The activity of the ornithine decarboxylase formed and the stability of the protein to degradation in a reticulocyte lysate system were determined. Changes of lysine-169 or of histidine-197 to alanine completely abolished enzyme activity, indicating that these residues are essential for enzyme activity. The removal of the C-terminal 36 residues, the mutation of lysine-349 to alanine, of lysine-298 to alanine or the double change of serine-303 and glutamic acid-308 to alanine residues still resulted in an active enzyme. The last-mentioned finding indicates that the phosphorylation of serine-303 does not play an essential role in the catalytic activity of ornithine decarboxylase. The control ornithine decarboxylase protein was degraded rapidly in a reticulocyte lysate provided that ATP was added. The truncated protein missing the 36 residues from the C-terminus was much more stable in this system, and the protein containing the double change of serine-303 and glutamic acid-308 to alanine residues was slightly more stable than control ornithine decarboxylase protein. These results indicate that the altered residues may play a role in interaction with factors responsible for the rapid turnover of ornithine decarboxylase.
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PMID:Identification of residues in ornithine decarboxylase essential for enzymic activity and for rapid protein turnover. 187 2

Several years ago, we proposed that polypeptide regions rich in proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) target intracellular proteins for destruction (Rogers, S., Wells, R., and Rechsteiner, M. (1986) Science 234, 364-368). To test the PEST hypothesis, we have produced chimeric proteins in which the N or C terminus of mouse dihydrofolate reductase is extended by the PEST-containing C terminus of mouse ornithine decarboxylase. Oligonucleotides encoding the 37 C-terminal residues of mouse ornithine decarboxylase (mODC) or equivalent lengths of dissimilar amino acids were inserted at appropriate sites in a dihydrofolate reductase (DHFR) expression vector. The various fusion proteins were expressed in Escherichia coli and purified to homogeneity by enzyme affinity chromatography. All purified fusion proteins exhibited similar abilities to convert dihydrofolate to tetrahydrofolate, thereby demonstrating that the attachment of peptide extensions to either terminus did not prevent the proper folding of DHFR. Metabolic stabilities of the radioiodinated fusion proteins were assayed in rabbit reticulocyte lysate or Xenopus egg extract. Proteolysis was found to be energy-dependent with mODC-DHFR fusion proteins being degraded from 2 to almost 40-fold faster than the parental DHFR molecule or DHFR fusion proteins bearing non-PEST extensions. Deletion of most of the PEST region from the mODC extension resulted in a significantly more stable fusion protein. Rapid proteolysis of DHFR proteins containing intact mODC extensions provides support for the PEST hypothesis.
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PMID:The C terminus of mouse ornithine decarboxylase confers rapid degradation on dihydrofolate reductase. Support for the pest hypothesis. 204 Jun 28

The constituent amino acids of reduced glutathione (GSH), GSH itself, and D-alpha-tocopherol inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermis in vivo and in vitro. The inhibitory effects of cysteine (Cys), GSH and D-alpha-tocopherol on ODC induction were proportional to their abilities to decrease the incidence of skin tumors in the initiation-promotion protocol. Moreover, the ability of the constituent amino acids of GSH and GSH to inhibit TPA-induced ODC activity correlated well with their ability to increase the ratio of GSH/oxidized glutathione (GSSG) in isolated epidermal cells. In vitro, various treatments with 1 mM GSH, 1 mM glutamic acid (Glu), 1 mM glycine (Gly), 0.4 mM Cys and/or 0.2 mM cystine (CysCys) inhibited dramatically the sharp decline in the intracellular ratio of GSH/GSSG caused by 0.1 microM TPA. Since the inhibitory effects of Cys on both the decrease in the ratio of GSH/GSSG and the induction of ODC activity by TPA were greatly reduced by the inhibitors of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase, it is suggested that some of the inhibitory effects of Glu, Cys and Gly on tumor promotion could result from their interference with the metabolism of the tripeptide GSH, a natural antioxidant which inhibits chemical carcinogenesis. The free radical scavenger D-alpha-tocopherol, which did not alter directly the intracellular ratio of GSH/GSSG, also prevented completely the decrease in the ratio of GSH/GSSG caused by TPA. These results, therefore, suggest that GSH level-raising agents and other antioxidants might inhibit by diverse means the effects of TPA on GSH metabolism and skin tumor promotion.
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PMID:Inhibitory effects of glutathione level-raising agents and D-alpha-tocopherol on ornithine decarboxylase induction and mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 285 27

The induction of ornithine decarboxylase (EC 4.1.1.17) (ODC) by amino acids and by the peptide hormones nerve growth factor (NGF) and epidermal growth factor (EGF) in salts-glucose media has been studied. Only those neutral amino acids taken into the cell via one of the Na+ dependent transport systems stimulate ODC activity. Asparagine and the nonmetabolizable alpha-amino-isobutyric acid (AIB) were used as representatives of this class of inducing amino acids, and their intracellular concentrations were related to the levels of ODC induced. A threshold intracellular concentration of asparagine or AIB has to be attained before ODC can be induced. Further slight increases in intracellular concentrations of asparagine or AIB produce disproportionately large increases of ODC, resulting in a sigmoidal curve of ODC induction. These results, and the fact that the decrease in ODC levels caused by valine is associated with a concurrent decrease in the intracellular level of the inducing amino acid, suggest that the intracellular amino acid level is causally related to the induction of ornithine decarboxylase. Glutamic acid, EGF, and NGF do not induce ODC except in the presence of an inducing amino acid. They act synergistically with the inducing amino acid and produce higher ODC levels at the same intracellular concentration of the inducing amino acid.
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PMID:The effect of transport system A and N amino acids and of nerve and epidermal growth factors on the induction of ornithine decarboxylase activity. 285 93

Enzymatic hydrolysis of 27 different chromogenic substrates and the assimilation of 44 carbon sources by 144 strains of Vibrio species of clinical importance, Aeromonas hydrophila and Plesiomonas shigelloides were studied by standardized micromethods. Some classical biochemical tests were also performed using the test kit TTE-AS (Flow Laboratories GmbH, Meckenheim, FRG). Reading of results was done automatically by a photometer and test data were recorded and stored by a microcomputer. All species investigated could be differentiated using a set of 16 miniaturized biochemical tests which are: Indole production, esculin hydrolysis, lysine decarboxylase, ornithine decarboxylase, arginine dihydrolase, fermentation of sucrose, enzymatic hydrolysis of o-nitrophenyl-beta-D-galactopyranoside, gamma-L-glutamic acid-p-nitroanilide and the assimilation of L-arabinose, D-cellobiose, D-mannose, sucrose, D-mannitol, i-inositol, acetate and DL-lactate. Comparing the TTE-AS tests to conventional test results, 94.4% overall agreement was found. 87.6% of the miniaturized assimilation tests agreed to literature data. The described tests are easy to perform and seem to be suitable for routine laboratory use.
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PMID:Phenotypic differentiation of members of the family Vibrionaceae using miniaturized biochemical tests. 332 70

Some cultures of Escherichia coli BGA8, a mutant unable to synthesize putrescine, showed a change of behaviour and could grow almost equally well in either the absence or the presence of polyamines after repeated periods of polyamine starvation. Experiments in vivo with radioactive precursors showed that the bacteria which evaded the polyamine requirement had recovered their ability to synthesize putrescine from glucose or glutamic acid, but not from ornithine or arginine. These results are in agreement with the fact that the polyamine-independent cells were still deficient in the enzymes ornithine decarboxylase and agmatinase. Our findings seem to indicate the existence of a new pathway synthesize putrescine which does not involve ornithine or arginine as intermediates.
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PMID:A probable new pathway for the biosynthesis of putrescine in Escherichia coli. 352 93

At a concentration of 1.25 mM, 14 amino acids were capable of inhibiting the induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in isolated epidermal cells. The greatest percentages of inhibition of TPA-induced epidermal ornithine decarboxylase activity were as follows: cysteine, 98%; tryptophan, 74%; methionine, 64%; phenylalanine, 51%; glycine, 44%; asparagine, 43%; glutamic acid, 42%; leucine, 40%; and arginine, 39%. These amino acid treatments did not alter the time- and concentration-response curves for induction of ornithine decarboxylase activity by TPA. Moreover, there was no difference between the rates at which [3H]arginine, [3H]leucine, [3H]phenylalanine, [3H]methionine, [3H]tryptophan and [14C]cysteine were taken up by freshly isolated epidermal cells or incorporated into epidermal proteins. Arginine, phenylalanine and methionine inhibited the induction of ornithine decarboxylase activity by the tumor promoter to degrees comparable to those elicited by their analogs canavanine and homoarginine, beta-2-thienyl-DL-alanine, and ethionine, respectively. These amino acids and amino acid analogs did not alter the overall rate of protein synthesis. In contrast, both the amino acids and their analogs increased the rates of proteolysis in isolated epidermal cells, an effect which correlated well with the abilities of these different compounds to inhibit TPA-induced ornithine decarboxylase activity. Moreover, both methionine and phenylalanine decreased the half-life and increased the rate of heat denaturation of the TPA-induced enzyme, a result identical to that obtained after treatment with the analogs ethionine and beta-2-thienyl-DL-alanine, respectively. Taken together, these results suggest that millimolar concentrations of exogenous amino acids might induce the synthesis of abnormal proteins and nonfunctional enzymes. Therefore, it is speculated that the uptake of unbalanced amounts of amino acids into the epidermal target cells might alter the stability and the ultrastructure of the TPA-stimulated enzyme just as the amino acid analogs do.
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PMID:Comparison of the inhibitory effects of diverse amino acids and amino acid analogs on 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in isolated epidermal cells. 397 Sep 79

We have compared the effects of several amino acid treatments on the induction of ornithine decarboxylase activity and the accumulation of putrescine, spermidine, and spermine by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo and in vitro. Incubation of isolated epidermal cells with mM concentrations of glycine, asparagine, glutamic acid, canavanine, arginine, and/or lysine inhibited dramatically the induction of ornithine decarboxylase activity by the tumor promoter. These remarkable inhibitory effects were concentration-dependent and additive. Arginine and its analog, canavanine, inhibited to the same degree TPA-induced ornithine decarboxylase activity, and potentiated to the same extent the inhibitory effects of glutamic acid, asparagine, and glycine on this enzyme. However, the inhibitory effects of arginine and canavanine were not additive. Similar alterations of tumor promoter-induced epidermal ornithine decarboxylase activity were observed in vivo when 62.5 mumol of the amino acids were injected i.p. 2 h before the topical application of 8.5 nmol of TPA to mouse skin. The results suggest the possibility that treatments with glycine, asparagine, glutamic acid, and arginine, the amino acids that were the most effective in inhibiting the tumor promoter-induced accumulation of polyamines in vivo, may reduce the tumor-promoting ability of TPA.
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PMID:Effects of amino acid treatments on 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis in vivo and in vitro. 664 98

AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.
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PMID:Pancreatic tumoral cell line AR42J: an amphicrine model. 751 39

Common protein motifs between histidine decarboxylase (HDC) and ornithine decarboxylase (ODC) were detected by computational analysis. Mutants were generated and expressed in vitro. In both enzymes, terminal PEST-region-containing fragments are not essential for decarboxylation (PEST regions are sequence fragments enriched in proline, glutamic acid, serine and threonine residues in a hydrophilic fragment flanked by cationic amino acids). The substitution of a very well conserved histidine residue by alanine causes a severalfold increase of the apparent K(m) values for the respective substrates.
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PMID:Experimental evidence for structure-activity features in common between mammalian histidine decarboxylase and ornithine decarboxylase. 897 41


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