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

---

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

Previous reports from this laboratory have shown that supplementation of diets containing the optimal level (0.02%) of dietary inorganic sulfate (SO4(2-] with cysteine instead of methionine can affect several metabolic pathways. It is possible that these results reflect alterations in the biosynthesis of potent physiological compounds, the polyamines. Adult male albino rats were fed diets containing 15% casein and a constant level of inorganic sulfate (0.02%) supplemented with cysteine (0.505%) or methionine (0.62%). The polyamines (putrescine, spermidine and spermine) and the controlling enzymes for their biosynthesis ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMD) were evaluated in liver, kidney and brain tissue homogenates following a 17-day dietary period. Rats fed the diet supplemented with cysteine had increased ODC activity and decreased SAMD activity when compared to rats fed diets supplemented with methionine. Polyamine concentrations varied in tissues with a trend toward increasing amounts in animals fed the cysteine-supplemented diet. Based on these data, it appears that dietary cysteine stimulates the biosynthesis and increased tissue concentration of polyamines.
...
PMID:The influence of cysteine and methionine supplements on polyamine biosynthesis in the rat. 663 47

Four methionine analog inhibitors of methionine adenosyltransferase, the enzyme which catalyzes S-adenosylmethionine biosynthesis, were tested in cultured L1210 cells for their effects on cell growth, leucine incorporation, S-adenosylmethionine (AdoMet) formation and polyamine biosynthesis. The IC50 values were as follows: selenomethionine, 0.13 mM; L-2-amino-4-methoxy-cis-but-3-enoic acid (L-cis-AMB), 0.4 mM; cycloleucine, 5 mM and 2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, 5 mM. At IC50 levels, the analogs significantly reduced AdoMet pools by approximately 50% while not similarly affecting leucine incorporation or polyamine biosynthesis. In combination with inhibitors of polyamine biosynthesis, growth inhibition was greatly increased with methylglyoxal bis(guanylhydrazone), an inhibitor of AdoMet decarboxylase, but only slightly increased with alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase. Overall, the data indicate that the methionine analogs, and particularly L-cis-AMB, seem to inhibit cell growth by interference with AdoMet biosynthesis. Since polyamine biosynthesis is not affected, the antiproliferative effect may be mediated through perturbations of certain transmethylation reactions.
...
PMID:Growth inhibition by methionine analog inhibitors of S-adenosylmethionine biosynthesis in the absence of polyamine depletion. 674 38

1. Direct or indirect inhibitors of l-ornithine decarboxylase (EC 4.1.1.17), structurally related or unrelated to l-ornithine, including dl-alpha-difluoromethylornithine, alpha-methylornithine and 1,3-diaminopropane, used alone or in combination, decreased polyamine concentrations in rat hepatoma tissue culture (HTC) cells and increased S-adenosyl-l-methionine decarboxylase activity (EC 4.1.1.50). 2. Comparison of the catalytic properties of S-adenosyl-l-methionine from cells with elevated and normal activities revealed no apparent modification of the catalytic site as judged by affinity for the substrate, stimulation by di- and tri-amines and inhibition by methylglyoxal bis-(guanylhydrazone). 3. Actinomycin D and cycloheximide, and RNA and a proteinsynthesis inhibitor respectively, blocked the increase of S-adenosyl-l-methionine decarboxylase activity elicited by alpha-difluoromethylornithine. In polyamine-depleted cells the apparent half-life of elevated S-adenosyl-l-methionine decarboxylase activity, determined by inhibition of protein synthesis, was 2.5-fold longer than in control cells. The present results suggest that elevation of S-adenosyl-l-methionine decarboxylase activity by alpha-difluoromethylornithine is due to stabilization of the enzyme. 4. Restoration of the normal intracellular putrescine content, by addition of putrescine to the medium of polyamine-deficient cells, transiently increased S-adenosyl-l-methionine decarboxylase activity. Thereafter, intracellular conversion of putrescine into spermidine was accompanied by inactivation of the enzyme at a rate that was similar to that found on addition of spermidine itself. No relationship between total intracellular spermine content and S-adenosyl-l-methionine decarboxylase activity could be established. 5. Addition of 1mm-1,3-diaminopropane to polyamine-deficient cells did not cause a decrease in the activity of S-adenosyl-l-methionine decarboxylase, whereas addition of 1,5-diaminopentane (cadaverine) did. 1,3-Diamino-N-(3-aminopropyl)propane did not accumulate in cells treated with alpha-difluoromethylornithine and 1,3-diaminopropane, whereas addition of 1,5-diaminopentane led to the accumulation of 1,5-diamino-N-(3-aminopropyl)pentane. 1,3-Diamino-N-(3-aminopropyl)propane (10mum) was as effective as spermidine in decreasing S-adenosyl-l-methionine decarboxylase activity. Thus effectiveness of a diamine in decreasing enzyme activity is related to its capability of being converted into a closely structurally related homologue of spermidine by spermidine synthase. 6. The spermidine site of action appears to be post-translational since (a) the spermidine-induced decrease of S-adenosyl-l-methionine activity was not prevented by actinomycin D and (b) spermidine in the presence of cycloheximide led to a synergistic inactivation of the enzyme with a decay rate that progressively approached control values. Altogether these results are indirect evidence for a strict negative control of S-adenosyl-l-methionine decarboxylase by spermidine and substantiate previous findings [Mamont, Duchesne, Grove & Tardif (1978) Exp. Cell Res.115, 387-393]. Spermidine appears to act on some processes involved in denaturation and/or degradation of the enzyme protein. Putrescine appears to decrease the rate of these processes. The physiological significance of the regulatory control of S-adenosyl-l-methionine decarboxylase is discussed.
...
PMID:Indirect evidence for a strict negative control of S-adenosyl-L-methionine decarboxylase by spermidine in rat hepatoma cells. 679 4

Biological transmethylation reactions and polyamine biosynthesis share the substrate S-adenosyl-L-methionine. Under normal conditions, decarboxylated S-adenosyl-L-methionine, the aminopropyl donor for polyamine biosynthesis, does not accumulate because of its rapid utilization in spermidine and spermine synthesis. Alteration of polyamine synthesis by DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of L-ornithine decarboxylase, leads to a striking accumulation of decarboxylated S-adenosyl-L-methionine in rat hepatoma cells cultured in vitro and in rat ventral prostate. This increase is due both to lack of putrescine and spermidine for the aminopropyltransferase reactions and to the elevation of S-adenosyl-L-methionine decarboxylase activity. The biological implications of accumulation of decarboxylated S-adenosyl-L-methionine are discussed with regard to the regulation of S-adenosyl-L-methionine decarboxylase activity and to the antiproliferative effects of DL-alpha-difluoromethylornithine.
...
PMID:Accumulation of decarboxylated S-adenosyl-L-methionine in mammalian cells as a consequence of the inhibition of putrescine biosynthesis. 680 35

The polyamine content of the skin of BALB/c and C3H mice was determined at intervals, after injecting Leishmania tropica major. In BALB/c mice, putrescine and spermidine levels increased three- to seven-fold; in C3H mice, spontaneous recovery occurred after 3 weeks, accompanied by a reduction in putrescine and spermidine levels. Ornithine decarboxylase activity was negligible in normal, uninfected skin of both BALB/c and C3H mice, but increased steadily during infection. Treatment with drugs that inhibit the growth of leishmanial amastigotes in the skin of mice also reduced polyamine levels and ornithine decarboxylase activity of previously infected skin. There was a close correlation between the therapeutic activity of the drugs and their effect on polyamine content and synthesis. The aminoglycoside paromomycin, which was chemotherapeutically more effective than pentamidine, also had a greater effect on polyamine levels. S-adenosyl-L-Methionine decarboxylase activity in the skin of BALB/c and C3H mice was only slightly affected by the parasites. Polyamine levels and ornithine decarboxylase activity could possibly serve as means for measuring the growth of leishmanial parasites in skin and other tissues and as a measure of the efficacy of anti-leishmanial chemotherapeutics.
...
PMID:Leishmania tropica major: effect of paromomycin and pentamidine on polyamine levels in the skin of normal and infected mice. 685 66

The comparative effects of the subchronic administration to rats of ethionine-supplemented and of chemically defined methyl-deficient diets on the hepatic levels of S-adenosylmethionine (SAM) and of ornithine decarboxylase (ODC), an enzyme marker of cell proliferation, were studied. Both treatments led to decreased hepatic levels of SAM and to marked increased activities in ODC. Both systems led to significant inverse correlations between ODC and SAM. In rats fed the methyl-deficient diets, hepatic levels of SAM were generally proportional to the dietary content of methionine and choline. The metabolic increases in S-adenosylmethionine decarboxylase (SAMDC) observed in the livers of methyl-deficient rats were proportional to the changes seen in ODC.
...
PMID:An inverse correlation between hepatic ornithine decarboxylase and S-adenosylmethionine in rats. 729 30

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed.
...
PMID:The influence of nerve section on the metabolism of polyamines in rat diaphragm muscle. 731 98

A number of bis(benzyl)polyamine analogs were found to be potent inhibitors of Leishmania donovani growth in vitro (IC50 = 4.3-25 microM). Structural variations appear to have important effects on the biological functions of these analogs. Subinhibitory concentration of all of the analogs with the exception of MDL 27994 could rescue the cells from DL-alpha-difluoromethylornithine toxicity. The analogs inhibited macromolecular synthesis as evaluated by [3H]thymidine, [14C]uracil, and [35S]methionine incorporation. They inhibited the activity of the two enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), involved in the biosynthesis of polyamines. These analogs depleted intracellular levels of natural polyamines. We conclude, therefore, that the major mechanism by which these analogs act may be by disruption of macromolecular biosynthesis and cell death. Repression of polyamines by these analogs may be yet another factor involved in slowing the growth of the parasite.
...
PMID:Effects of bis(benzyl)polyamine analogs on Leishmania donovani promastigotes. 762 65

The metabolism of [35S]methionine in cultured bloodstream forms of African trypanosomes was followed using flow-through radiodetection linked to liquid chromatography separation. The effects of a transmethylase inhibitor, sinefungin, and of the ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine (Ornidyl; DFMO), on methionine metabolism were also observed. Trypanosomes rapidly incorporated [35S]methionine into S-adenosylmethionine (AdoMet) and the metabolites methylthioadenosine, S-adenosylhomocysteine, homocysteine, cystathionine cysteine and glutathione. Untreated trypanosomes excreted large quantities of cystathionine and cysteine into the growth medium. DFMO-treated cells formed larger quantities of AdoMet more rapidly than did control cells, as was evident from initial time points (30 min and 1 h). Decarboxylated AdoMet, present in trace quantities in control cells, accumulated in DFMO-treated cells. Sinefungin increased the AdoMet concentrations approximately 20-fold over that of controls after a 6 h incubation with [35S]methionine, while cystathionine and cysteine levels decreased. The half-life (t1/2) and rate of turnover of AdoMet were measured in cells treated with DFMO or sinefungin. DFMO treatment caused a substantial increase in the rate of AdoMet utilization, while sinefungin extended the t1/2 and lowered AdoMet turnover. These studies show that trypanosomes rapidly metabolize methionine through AdoMet to intermediates of the polyamine and transmethylation pathways. Agents inhibiting these pathways rapidly affect the concentration and rate of utilization of AdoMet, significantly changing the concentrations of metabolites.
...
PMID:Fate of soluble methionine in African trypanosomes: effects of metabolic inhibitors. 763 87

Studies are reviewed that report consumption of soy protein diets inhibits the growth of various tumors in rats. The inhibitory effect has been attributed to the phytoestrogens (genistein and diadzein) or protein kinase inhibitor in soy protein products. Recent studies indicate that additional factors in soy protein products may also contribute to the inhibition of tumorigenesis, namely the deficiency of the essential amino acid methionine. Metastatic growth to the lungs of a primary rhabdomyosarcoma tumor was inhibited by feeding a soy protein diet. The effect was reversed by methionine fortification of the diet. Carcinogen-induced mammary tumor development was inhibited during the promotional phase in rats fed soy protein isolate diet and reversed with a methionine-supplemented diet. Additional studies demonstrated that after excision of the primary mammary tumor, growth of additional tumors was inhibited when the diet was changed from casein to soy protein isolate. Histopathologic evaluation of the mammary tumors revealed more benign fibroadenomas and lower-grade adenocarcinomas in the soy protein group. Before carcinogen administration (at 7 weeks of age), ornithine decarboxylase activity and polyamine concentrations in the rat mammary epithelium were significantly lower in the soy protein group. These data suggest an inhibitory effect on mammary epithelial growth in the soy-protein-fed group.
...
PMID:Soy and experimental cancer: animal studies. 788 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---