Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-Adenosylmethionine metabolism and its relation to the synthesis and accumulation of polyamines was studied in rat liver under various nutritional conditions, in adrenalectomized or partially hepatectomized animals and after treatment with cortisol, thioacetamide or methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidine)dinitrilo]diguanidine}. Starvation for 2 days only slightly affected S-adenosylmethionine metabolism. The ratio of spermidine/spermine decreased markedly, but the concentration of total polyamines did not change significantly. The activity of S-adenosylmethionine decarboxylase initially decreased and then increased during prolonged starvation. This increase was dependent on intact adrenals. Re-feeding of starved animals caused a rapid but transient stimulation of polyamine synthesis and also increased the concentrations of S-adenosylmethionine and S-adenosylhomocysteine. Similarly, cortisol treatment enhanced the synthesis of polyamines, S-adenosylmethionine and S-adenosylhomocysteine. Feeding with a methionine-deficient diet for 7-14 days profoundly increased the concentration of spermidine, whereas the concentrations of total polyamines and of S-adenosylmethionine showed no significant changes. The results show that nutritional state and adrenal function play a significant role in the regulation of hepatic metabolism of S-adenosylmethionine and polyamines. They further indicate that under a variety of physiological and experimental conditions the concentrations of S-adenosylmethionine and of total polyamines remain fairly constant and that changes in polyamine metabolism are not primarily connected with changes in the accumulation of S-adenosylmethionine or S-adenosylhomocysteine.
 ...
PMID:S-adenosylmethionine metabolism and its relation to polyamine synthesis in rat liver. Effect of nutritional state, adrenal function, some drugs and partial hepatectomy. 59 68

Ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase activity (SAMD) were measured in tumour tissue in mice during periods of starvation (24 h) and refeeding. Starvation led to a 60% reduction in tumour ODC activity. Refeeding normalised the activity within 4 h. Restitution in ODC activity, representing de novo enzyme synthesis, preceded DNA resynthesis. SAMD activity continued to fall along the increase in ODC activity during refeeding, while difluoro-methyl-ornithine (DFMO) caused a compensatory increase in SAMD activity as expected. A fall and regain in ODC activity was associated with inhibition and regrowth of the tumour. Starvation-refeeding was not related to any decrease in tumour polyamine concentrations, while systemic DFMO blockade was. Glucose stimulated ODC when refed orally, but not when given systemically. Tumour ODC activity was not decreased in refed mice by anti-insulin, a procedure that antagonised insulin's bioactivity. Exogenous insulin did not stimulate tumour ODC activity. Our results suggest that gastrointestinal metabolism of carbohydrates stimulates the release of a factor, which initiates both ODC activity and DNA synthesis in tumour cells. This factor was not insulin.
 ...
PMID:Ornithine decarboxylase activity in mouse tumour tissue in response to refeeding and diet components. 183

1. Starvation caused a marked decrease in the activity of ornithine decarboxylase in mammary gland, together with a lesser decrease in the activity of S-adenosylmethionine decarboxylase and a marked fall in milk production. Liver ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were unaffected. 2. Refeeding for 2.5 h was without effect on ornithine decarboxylase in mammary gland, but it returned the S-adenosylmethionine decarboxylase activity in mammary gland to control values and elevated both ornithine decarboxylase and S-adenosylmethionine decarboxylase in liver. 3. Refeeding for 5 h returned the activity of ornithine decarboxylase in mammary gland to fed-state values and resulted in further increases in S-adenosylmethionine decarboxylase in mammary gland and liver and in ornithine decarboxylase in liver. 4. Prolactin deficiency in fed rats resulted in decreased milk production and decreased activity of ornithine decarboxylase in mammary gland. The increase in ornithine decarboxylase activity normally seen after refeeding starved rats for 5 h was completely blocked by prolactin deficiency. 5. In fed rats, injection of streptozotocin 2.5 h before death caused a decrease in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in mammary gland, which could be reversed by simultaneous injection of insulin. Insulin deficiency also prevented the increase in S-adenosylmethionine decarboxylase in liver and mammary gland normally observed after refeeding starved rats for 2.5 h.
 ...
PMID:Regulation of the activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase in mammary gland and liver of lactating rats. Effects of starvation, prolactin and insulin deficiency. 704 36

We recently isolated a Chinese hamster ovary cell line which grows well without serum but requires the exogenous polyamines putrescine, spermidine or spermine for continuous replication. Here we show that these cells are defective in the arginase-catalyzed synthesis of ornithine, the precursor of polyamines, and that ornithine can replace polyamines in the medium for supporting growth of the cells. The activities of two other key enzymes of polyamine biosynthesis, ornithine decarboxylase and adenosylmethionine decarboxylase, are clearly detectable and show increase during polyamine starvation. In ornithine-and polyamine-free medium cellular putrescine and spermidine are rapidly depleted while the concentration of spermine decreases only moderately. We show further that the cells are able to grow in serum-containing medium without added ornithine or polyamines. This is explained by our finding that serum contains arginase which synthesizes ornithine from arginine in the medium. All the sera from different animal species tested contained arginase activity although in greatly varying amounts. Serum-free medium is therefore essential for expression of arginase deficiency in cells in tissue culture. The eventual importance of polyamines for serum-free cultures in general is discussed.
 ...
PMID:Polyamine dependence of Chinese hamster ovary cells in serum-free culture is due to deficient arginase activity. 715 97

A temperature-sensitive (ts) cell cycle mutant of Chinese hamster fibroblasts with a block in G1 was investigated. Attention was on the expression of the activity of three enzymes: ornithine decarboxylase (ODC) S-adenosylmethionine decarboxylase (SAMDC), and thymidine kinase (TK). ODC and SAMDC activities are normally induced in the middle of, or late in, the G1 phase, while TK activity starts to appear at the G1/S boundary. In the ts mutant released from serum starvation at the nonpermissive temperature (40.8 degrees C), we find no effect on the expression of SAMDC activity, a significantly reduced level of ODC activity compared to the control at the permissive temperature (34 degrees C), and no induction of TK activity. Results presented here and in a previous publication (Landy-Otsuka and Scheffler, '78) suggest that the decrease in ODC activity is due to an effect of the nonpermissive temperature on a post-transcriptional step, possibly a very rapid inactivation of the enzyme. The absence of TK activity, on the other hand, appears to be due to a block in transcription at the nonpermissive temperature.
 ...
PMID:Enzyme induction in a temperature-sensitive cell cycle mutant of Chinese hamster fibroblasts. 746 27

We used differential display analysis to identify mRNAs responsive to changes in polyamine synthesis. As an overproducing model we used the kidneys of transgenic hybrid mice overexpressing ornithine decarboxylase and S-adenosylmethionine decarboxylase, two key enzymes in polyamine biosynthesis. To identify mRNAs that respond to polyamine starvation, we treated Rat-2 cells with alpha-difluoromethylornithine, a specific inhibitor of polyamine biosynthesis. We isolated 41 partial cDNA clones, representing 37 differentially expressed mRNAs. Of these, 15 have similarity with known genes, five appear to be similar to reported expressed sequence tags and seventeen clones were novel sequences. Of the 35 mRNAs expressed differentially after alpha-difluoromethylornithine treatment, 26 were up-regulated. The expression of only three mRNAs was altered in the transgenic animals and all three were down-regulated. Determination of mRNA half-life of three of the mRNAs up-regulated in response to polyamine depletion revealed that the accumulation results from stabilization of the messages. Because most of the transcripts identified from Rat-2 cells suffering polyamine starvation were accumulated, we conclude that polyamine depletion, while blocking cell growth, is stabilizing mRNAs. This may be due to the lack of spermidine for post-translational modification of the eukaryotic initiation factor 5A, which plays a major role in mRNA turnover. The coupling of mRNA stabilization with cell-growth arrest in response to polyamine starvation provides cells with an economical way to resume growth after recovery from polyamine deficiency.
 ...
PMID:Changes in gene expression in response to polyamine depletion indicates selective stabilization of mRNAs. 1065 56

Polyamines are essential for cell growth of eukaryotes including the etiologic agent of human African trypanosomiasis (HAT), Trypanosoma brucei. In trypanosomatids, a key enzyme in the polyamine biosynthetic pathway, S-adenosylmethionine decarboxylase (TbAdoMetDC) heterodimerizes with a unique catalytically-dead paralog called prozyme to form the active enzyme complex. In higher eukaryotes, polyamine metabolism is subject to tight feedback regulation by spermidine-dependent mechanisms that are absent in trypanosomatids. Instead, in T. brucei an alternative regulatory strategy based on TbAdoMetDC prozyme has evolved. We previously demonstrated that prozyme protein levels increase in response to loss of TbAdoMetDC activity. Herein, we show that prozyme levels are under translational control by monitoring incorporation of deuterated leucine into nascent prozyme protein. We furthermore identify pathway factors that regulate prozyme mRNA translation. We find evidence for a regulatory feedback mechanism in which TbAdoMetDC protein and decarboxylated AdoMet (dcAdoMet) act as suppressors of prozyme translation. In TbAdoMetDC null cells expressing the human AdoMetDC enzyme, prozyme levels are constitutively upregulated. Wild-type prozyme levels are restored by complementation with either TbAdoMetDC or an active site mutant, suggesting that TbAdoMetDC possesses an enzyme activity-independent function that inhibits prozyme translation. Depletion of dcAdoMet pools by three independent strategies: inhibition/knockdown of TbAdoMetDC, knockdown of AdoMet synthase, or methionine starvation, each cause prozyme upregulation, providing independent evidence that dcAdoMet functions as a metabolic signal for regulation of the polyamine pathway in T. brucei. These findings highlight a potential regulatory paradigm employing enzymes and pseudoenzymes that may have broad implications in biology.
 ...
PMID:A dual regulatory circuit consisting of S-adenosylmethionine decarboxylase protein and its reaction product controls expression of the paralogous activator prozyme in Trypanosoma brucei. 3036 68