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 biosynthesis of L-ornithine decarboxylase was investigated in 73 strains of the Vibrionaceae family. V. harveyi 1175 was found to be most active. The maximum accumulation of the enzyme was observed after 4-hour cultivation at pH 5.5 and 33 degrees in the presence of 0.8% L-ornithine HCl used as an inducer without aeration. Under these conditions L-ornithine decarboxylase activity was 3.87 units/mg dry cells.
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PMID:[Biosynthesis of inducible L-ornithine decarboxylase by bacterial of the Vibrionaceae family]. 203 4

The objective of this study was to evaluate induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, and subsequent polyamine accumulation in interleukin-2 (IL-2)- and interleukin-3 (IL-3)-dependent growth. The CTLL-20 and FDC-P1 cell lines, which have been shown to be absolutely dependent on IL-2 and IL-3, respectively, were used in these studies. The CTLL-20 and FDC-P1 cells each had different temporal patterns of ODC induction following lymphokine stimulation. ODC levels increased rapidly in the FDC-P1 cells, peaking 4 hr after stimulation with IL-3. In contrast, peak ODC activity in the CTLL-20 cells occurred 18 hr following stimulation with IL-2 and reached eightfold higher levels than those observed in the FDC-P1 cells. Treatment with D,L-alpha-difluoromethylornithine X HCl X H2O (DFMO), a specific irreversible inhibitor of ODC activity, completely abrogated lymphokine-dependent ODC induction in both the CTLL-20 and FDC-P1 cell lines. Similarly, intracellular levels of the polyamines putrescine and spermidine were reduced in both cell lines following DFMO treatment. DFMO treatment reduced both IL-2- and IL-3-dependent proliferation in a dose-dependent manner. However, this inhibition could be reversed by the addition of exogenous putrescine. DFMO treatment had no effect on cell viability. Polyamine-depleted CTLL-20 and FDC-P1 cells showed decreased absorption of IL-2 and IL-3 activity, respectively. However, the addition of exogenous putrescine restored the ability of the cells to absorb the appropriate lymphokine. These data are the first to demonstrate that ODC induction and polyamine biosynthesis are required in lymphokine dependent growth.
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PMID:Ornithine decarboxylase induction and polyamine biosynthesis are required for the growth of interleukin-2- and interleukin-3-dependent cell lines. 309 95

Hypertonic NaCl increases the activity of gastric mucosal ornithine decarboxylase (ODC). Intragastric administration of concentrated NaCl solution also induces ulcers in the glandular gastric mucosa. The relationship between ODC activity and gastric mucosal damage and the significance of ODC increases in hypertonic NaCl-treated rats are unknown. Rats were fasted 24 h before being given 1.0 ml of 3.4 M NaCl, 120 mM aspirin in 100 mM HCl or 50% ethanol intragastrically. The oxyntic gland mucosa was removed and assayed for ODC and in some experiments DNA, RNA, and protein content. DNA, RNA, and protein content were decreased by 3.4 M NaCl, and these decreases were much greater if ODC was inhibited by pretreatment with alpha-difluoromethylornithine (DFMO). Both aspirin and 3.4 M NaCl induced ODC activity 6 h later. However, DFMO increased the lesion index only in NaCl-treated rats. Although ethanol produced damage, it had no effect on ODC levels, and DFMO did not alter the severity of ethanol lesions. When different concentrations (0.4, 0.8, 1.6, 2.5, and 3.4 M) of NaCl were administered, ODC activities were increased 6 h later in rats receiving 1.6, 2.5, and 3.4 M NaCl but not lower concentrations. Gross lesions appeared in response to the 2.5 M dose and increased with increasing NaCl concentration. However, microscopic damage of the gastric mucosa occurred at all the concentrations tested. These data show that 1) ODC activation is not necessarily produced by damage, 2) in the case of NaCl, increasing damage increases ODC, and 3) ODC appears to have a role in the prevention of a recovery to damage caused by NaCl.
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PMID:Relationship between ornithine decarboxylase activity and gastric damage. 311 Dec 73

Eflornithine-HCl (alpha-difluoromethylornithine or DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity in cell culture and animal tumor models. This phase I study was designed to determine and compare toxicity and the maximally tolerated dose of a 4-day course of DFMO given to patients in oral, continuous intravenous infusion or pulse intravenous infusion forms. Twenty-four patients were entered into this study: 8 received intravenous pulse drug, 10 intravenous continuous infusion of drug, and 6 oral DFMO. The most frequent toxicity was nausea and vomiting which occurred in 9 courses of oral drug. Only two patients receiving intravenous DFMO had nausea and vomiting. Clinically significant thrombocytopenia and audiometric abnormalities were not encountered in contrast to previous experience with 28-day courses of oral DFMO. The maximally tolerated dose of a four-day course of oral DFMO was 3.75 gm/M2 every 6 hours. The maximally tolerated dose of intravenous pulse and continuous infusion DFMO was not attained. Pharmacokinetic studies demonstrated that the intravenous schedules achieved higher plasma levels of DFMO than those previously obtained with chronic oral dosing.
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PMID:Phase I trial and pharmacokinetic study of intravenous and oral alpha-difluoromethylornithine. 311 11

When rat liver homogenate or its postmitochondrial supernatant was incubated with L-cysteine, but not D-cysteine, ornithine decarboxylase (ODC) lost more than half of its catalytic activity within 30 min and, at a slower rate, its immunoreactivity. The inactivation correlated with production of H2S during the incubation. These changes did not occur in liver homogenates from vitamin B6-deficient rats. A heat-stable inactivating factor was found in both dialysed cytosol and washed microsomes obtained from the postmitochondrial supernatant incubated with cysteine. The microsomal inactivating factor was solubilized into Tris/HCl buffer, pH 7.4, containing dithiothreitol. Its absorption spectrum in the visible region resembled that of Fe2+ X dithiothreitol in Tris/HCl buffer. On the other hand FeSO4 inactivated partially purified ODC in a similar manner to the present inactivating factor. During the incubation of postmitochondrial supernatant with cysteine, there was a marked increase in the contents of Fe2+ loosely bound to cytosolic and microsomal macromolecules. Furthermore, the content of such reactive iron in the inactivating factor preparations was enough to account for their inactivating activity. These data suggested that H2S produced from cysteine by some vitamin B6-dependent enzyme(s) converted cytosolic and microsomal iron into a reactive loosely bound form that inactivated ODC.
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PMID:Cysteine-dependent inactivation of hepatic ornithine decarboxylase. 669 45

Weanling male rats were fed diets that varied in protein quality (casein or wheat gluten) and vitamin B-6 (0.0, 0.5, 1.0 and 1.5 mg pyridoxine HCl/kg diet) to test the hypotheses that low protein quality would depress vitamin B-6 nutritional status and that activity of ornithine decarboxylase (ODC) would be a sensitive functional indicator of vitamin B-6 nutritional status. The wheat gluten diet depressed body weight gain approximately 17% at higher vitamin B-6 levels, as expected. However, vitamin B-6 nutritional status was not worse in gluten-fed compared with casein-fed groups, as evidenced by static measures (B-6 vitamer concentrations in plasma and tissues) and a functional indicator (tryptophan load test). The activity of ODC (holo- and total) in liver, kidney and small intestine did not vary significantly at the three higher levels of vitamin B-6 intake. In groups fed casein, total ODC activity in these tissues was two- to fivefold higher in rats fed diets containing 0.0 mg vitamin B-6/kg compared with higher B-6 levels, without corresponding differences in ODC mRNA abundance in liver and kidney. Concentrations of B-6 vitamers (except pyridoxal phosphate in plasma) increased linearly with dietary vitamin B-6 in plasma, liver, kidney and intestine. These data suggest that low quality protein fed as wheat gluten suppresses growth but not vitamin B-6 nutritional status, and that ODC activity is not a sensitive functional indicator of marginal vitamin B-6 status.
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PMID:Dietary protein quality alters ornithine decarboxylase activity but not vitamin B-6 nutritional status in rats. 764 55

In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31%+/-6%) as compared with that in control animals infused with NSS (15%+/-4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4+/-4 rete pegs per 100 microm of esophageal length) or in animals examined 24 hours after acid exposure (4+/-2 rete pegs per 100 microm). However, rete pegs were very prominent 48 hours after acid infusion (22+/-6 rete pegs per 100 microm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.
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PMID:Acute acid exposure increases rabbit esophageal cell proliferation. 948 99

Eflornithine HCl 13.9% cream is the first topical prescription treatment to be approved by the US FDA for the reduction of unwanted facial hair in women. It irreversibly inhibits ornithine decarboxylase (ODC), an enzyme that catalyzes the rate-limiting step for follicular polyamine synthesis, which is necessary for hair growth. In clinical trials eflornithine cream slowed the growth of unwanted facial hair in up to 60% of women. Improvement occurs gradually over a period of 4-8 weeks or longer. Most reported adverse reactions consisted of minor skin irritation.
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PMID:Vaniqa--eflornithine 13.9% cream. 1137 95

A release of (14)CO(2) not related to ornithine decarboxylase activity was found in crude leaf extracts from Lycopersicon esculentum, Avena sativa, and especially from the pyrrolizidine alkaloid-bearing Heliotropium angiospermum when incubated with [1-(14)C]- or [U-(14)C]ornithine. The total (14)CO(2) produced was about 5- to 100-fold higher than that due to ornithine decarboxylase activities calculated from labeled putrescine (Put) found by thin-layer electrophoresis in the incubation mixtures. Partial purification with (NH(4))(2)SO(4) did not eliminate completely the interfering decarboxylation. When incubated with labeled arginine, a very significant (14)CO(2) release not related to arginine decarboxylase activity was observed only in extracts from H. angiospermum leaves, especially in Tris.HCl buffer. Under the assay conditions, these extracts exhibited oxidative degradation of added Put and agmatine (Agm) and also revealed a high arginase activity. Amino-guanidine at 0.1 to 0.2 millimolar prevented Put degradation and greatly decreased oxidative degradation of Agm; ornithine at 15 to 20 millimolar significantly inhibited arginase activity. A verification of the reliability of the standard (14)CO(2)-based method by assessing labeled Put and/or Agm-formed in the presence of added aminoguanidine and/or ornithine when needed-is recommended especially when crude or semicrude plant extracts are assayed.When based on Put and/or Agm formed at 1.0 to 2.5 millimolar of substrate, the activities of ornithine decarboxylase and arginine decarboxylase in the youngest leaves of the tested species ranged between 1.1 and 3.6 and 1 and 1600 nanomoles per hour per gram fresh weight, respectively. The enzyme activities are discussed in relation to the biosynthesis of pyrrolizidine alkaloids.
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PMID:Assaying ornithine and arginine decarboxylases in some plant species. 1666 41