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

Resting rat thymocytes were stimulated to cell cycle entry and proliferation by the addition of concanavalin A and interleukin 2 to the culture medium. Maximal rats of DNA and RNA synthesis and of glycolysis with a 20-fold increase in glucose uptake were observed 48 h after stimulation. Glycolytic enzyme levels increased 3-8-fold, also reaching their maxima 48 h after mitogenic stimulation. Actinomycin D (1.3-1.5 ng/ml) completely inhibited DNA and RNA synthesis in 24- and 48-h cultured cells but showed no inhibitory effect on glycolytic enzyme induction or on enhanced glycolysis. These results suggest the presence of sufficient mRNAs for the synthesis of glycolytic enzymes even though transcription is abolished by actinomycin D. Ornithine decarboxylase activity increased rapidly up to 41-fold within 6 h after stimulation with concanavalin A and interleukin 2. This rapid increase could not be prevented by actinomycin D; however, ornithine decarboxylase activity of thymocytes was affected after 24- and 48-h culture periods. Inhibition of ornithine decarboxylase by 5 mM difluoromethylornithine completely abolished glycolytic enzyme induction. This inhibitory effect could be reversed by exogeneous putrescine. The results obtained indicate the importance of early ornithine decarboxylase activation and polyamine biosynthesis for the induction of glycolytic enzymes in proliferating thymocytes.
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PMID:Role of ornithine decarboxylase on glycolytic enzyme induction during thymocyte proliferation. 311 96

Cell-cycle progression of rat thymocytes stimulated with concanavalin A and interleukin 2 was monitored at 12-h intervals by pulse labeling aliquots of the cell culture with [3H]thymidine, by measuring cellular DNA and protein content and by counting the number of cells in the cultures. The cell cycle was completed after 96 h of culture with the S phase peaking at 48 h. Early events in thymocyte activation were enhanced phosphatidylinositol turnover and the induction of ornithine decarboxylase. Concomitant changes were observed in the rates of DNA synthesis and glycolysis accompanied by a 20-fold increase in glucose uptake 48 h after stimulation. However, the maximal increment in the glycolytic rate preceded that of DNA synthesis by 12 h. Apart from the quantitative changes which occurred during the cell-cycle progression, there was also a change from partial aerobic glucose degradation to CO2 (26%) to almost complete anaerobic conversion of glucose to lactate (85%) and less than 3% to CO2. Glycolytic enzyme levels increased fourfold to tenfold and reached their maxima 48 h after mitogenic stimulation. Maximal increments of glycolytic enzyme activities preceded or coincided with the maximal increments of the glycolytic rate. Actinomycin D (1.5 ng/ml) completely inhibited DNA and RNA synthesis but did not show any inhibitory effect either on glycolytic enzyme induction or on enhanced glycolysis. During mitosis and return of the cells to the non-proliferative state, all of the enhanced metabolic rates returned to their initial levels and the elevated enzyme activities were decreased also. The marked changes of metabolic rates and enzyme activities observed at the various phases of the cell cycle suggest that these biochemical events may also serve as suitable parameters for evaluating the response of lymphocytes towards mitogens and lymphokines.
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PMID:Cell-cycle-related metabolic and enzymatic events in proliferating rat thymocytes. 325 38

This paper reviews the inhibition of various enzymes by neuroleptics, anti-mycotics, antibiotics and other drugs on three species of human pathogenic amoebas, mainly Entamoeba histolytica, Acanthamoeba polyphaga and Naegleria fowleri, and their antiproliferative effects. A recent patent registered by Philip relates to the combination of an antibacterial formulation and antifungal agent for producing a therapeutically effective quantity of an antimicrobial that is suitable for suppressing or treating fungal growth. The rationale behind this patent focused on essential and valid targets with a description of the main pathogenic characteristics of these amoebas. The study of new targets, such as trypanothione and trypanothione reductase, and the drug effects of selected agents were arranged into six main groups: A) Inhibition of disulfide reducing enzymes by neuroleptics, antimycotics and antibiotics; B) Comparative evaluation of the efficacies of several drugs with antiproliferative activities; C) Inhibition of the enzymes for the synthesis of trypanothione, such as ornithine decarboxylase, spermidine synthase and trypanothione synthetase; D) Inhibition of the glycolytic enzyme PPi-dependent phosphofructokinase (PFK) from Entamoeba and Naegleria by pyrophosphate analogues, different from the host enzyme; E) Inhibition of enzymes secreted by these parasites to invade the human host, for example cysteine proteinases; and F) Inhibition of encystment pathways and cyst-wall assembly proteins.
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PMID:Drug effects on drug targets: inhibition of enzymes by neuroleptics, antimycotics, antibiotics and other drugs on human pathogenic amoebas and their anti-proliferative effects. 1822 Nov 78