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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maximum activities of some key enzymes of metabolism were studied in lungs of fed and 48-h-starved rats. The maximum activity of hexokinase in the lung is similar to that of other tissues of the body, but lower than that of phosphorylase and 6-phosphofructokinase. High activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were found in lung tissue, suggesting the importance of the pentose phosphate pathway in the lung. The activities of hexokinase and 6-phosphofructokinase were decreased whereas that of phosphorylase increased in response to starvation. Of the enzymes of the tricarboxylic acid cycle whose activities were measured, that of oxoglutarate dehydrogenase was the lowest, yet its activity (approximately 4.2 nmol/min per mg protein at 37 degrees C) was considerably greater than the flux through the cycle (0.46 nmol/min per mg protein at 37 degrees C; calculated from oxygen consumption by incubated lung slices). The activities of both oxoglutarate dehydrogenase and citrate synthase were decreased by starvation. The activities of 3-oxoacid CoA-transferase and acetoacetyl-CoA thiolase were low in lung tissue compared to those of other tissues (eg kidney, brain) and that of 3-hydroxybutyrate dehydrogenase was very low. The activity of carnitine palmitoyl transferase is higher in the lung, suggesting that fatty acids (and possibly acetoacetate) could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. Very low rates of utilization of 3-hydroxybutyrate were observed during incubation of lung slices, but that of oleate was 1.2 nmol/h per mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by lungs of the rat. 176

It has been found that there exists a correlation in the dynamics of changes in the amount of glutamate, alpha-ketoglutarate, glutamine, ammonia and activity level or alpha-ketoglutarate dehydrogenase, NADP-glutamate dehydrogenase, glutamine synthetase and glutaminase in the brain of young carp in the process of winter starvation. It has been stated that under condition of energy deficiency and meaningful amount of ammonia in the organism of hibernating fish, its binding parallel with the known glutamine synthetase mechanism may proceed in the course of the NADP-glutamate dehydrogenase reaction which balance is shifted towards the glutamate synthesis. This reaction is supposed to provide the outflow of alpha-ketoglutarate from the citric cycle, which intensifies energy deficiency of the organism.
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PMID:[Features of the interconversion of alpha-ketoglutarate--glutamate in brain mitochondria of exothermic animals during hibernation]. 198 77

Measurement of the arteriovenous differences for free amino acids across rat kidney reveals that glycine and citrulline are removed and serine and arginine are added to the circulation. In addition, glutamine is taken up in large quantities by kidneys of animals that need to excrete large quantities of acid (e.g., diabetic animals, NH4Cl-fed animals, and animals fed a high protein diet). Glutamine is the major precursor of urinary ammonia and thus renal glutamine metabolism plays a key role in acid-base homeostasis. This process occurs primarily in the cells of the convoluted proximal tubule. Glutamine carbon is converted to glucose in acidotic rats and is totally oxidized in dogs. Regulation of glutamine metabolism occurs at two levels: acute regulation and chronic regulation. Acute regulation is, in part, mediated through a fall in intracellular [H+]. This activates alpha-ketoglutarate dehydrogenase and, ultimately, glutaminase. Chronic regulation involves induction of key enzymes, including, in the rat, glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase. During the acidosis of prolonged starvation, the kidneys' requirement for glutamine must be met from muscle proteolysis and thus becomes a drain on lean body mass. Serine synthesis occurs by two separate pathways: from glycine by the combined actions of the glycine cleavage enzyme and serine hydroxymethyltransferase and from gluconeogenic precursors using the phosphorylated-intermediate pathway. Both pathways are located in the cells of the proximal tubule. Conversion of glycine to serine is ammoniagenic and the activity of the glycine cleavage enzyme is increased in acidosis. The function of serine synthesis by the phosphorylated-intermediate pathway is not apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1986 Borden award lecture. The role of the kidney in amino acid metabolism and nutrition. 332 68

1. Previous studies showed that the activation of pyruvate dehydrogenase within intact rat heart mitochondria of pyruvate is much diminished in mitochondria from starved or diabetic animals [see Kerbey, Randle, Cooper, Whitehouse, Pask & Denton (1976) Biochem. J. 154, 327-348]. In the present study, diminished responses to added Ca2+ and ADP were also found in these mitochondria. 2. Starvation or diabetes did not affect the mitochondrial respiratory control ratio of the ATP content. Moreover, starvation and diabetes did not alter the response of the intramitochondrial Ca2+-sensitive enzyme, 2-oxoglutarate dehydrogenase, to changes in the extramitochondrial concentration of Ca2+ and 2-oxoglutarate, thus indicating that there were no appreciable changes in the distribution of Ca2+ and H+ across the mitochondrial inner membrane. 3. Pyruvate, Ca2+ and ADP were found to have synergistic effects on pyruvate dehydrogenase activity, particularly in mitochondria from starved and diabetic rats. 4. The results suggest that the effects of diabetes and starvation on pyruvate dehydrogenase are not brought about by changes in the distribution of these effectors across the mitochondrial inner membrane or by changes in the intrinsic sensitivity of the kinase or phosphatase of the pyruvate dehydrogenase system to pyruvate, Ca2+ or ADP; rather it is probably that there is an increase in the maximum activity of kinase relative to that of the phosphatase. 6. The results also lend further support to the hypothesis that adrenaline may bring about the activation of pyruvate dehydrogenase in the rat heart by an increase in the intramitochondrial concentration of Ca2+.
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PMID:Studies on the interactions of Ca2+ and pyruvate in the regulation of rat heart pyruvate dehydrogenase activity. Effects of starvation and diabetes. 709 23

1. The maximum activity of hexokinase in lymphocytes is similar to that of 6-phosphofructokinase, but considerably greater than that of phosphorylase, suggesting that glucose rather than glycogen is the major carbohydrate fuel for these cells. Starvation increased slightly the activities of some of the glycolytic enzymes. A local immunological challenge in vivo (a graft-versus-host reaction) increased the activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and lactate dehydrogenase, confirming the importance of the glycolytic pathway in cell division. 2. The activities of the ketone-body-utilizing enzymes were lower than those of hexokinase or 6-phosphofructokinase, unlike in muscle and brain, and were not affected by starvation. It is suggested that the ketone bodies will not provide a quantitatively important alternative fuel to glucose in lymphocytes. 3. Of the enzymes of the tricarboxylic acid cycle whose activities were measured, that of oxoglutarate dehydrogenase was the lowest, yet its activity (about 4.0mumol/min per g dry wt. at 37 degrees C) was considerably greater than the flux through the cycle (0.5mumol/min per g calculated from oxygen consumption by incubated lymphocytes). The activity was decreased by starvation, but that of citrate synthase was increased by the local immunological challenge in vivo. It is suggested that the rate of the cycle would increase towards the capacity indicated by oxoglutarate dehydrogenase in proliferating lymphocytes. 4. Enzymes possibly involved in the pathway of glutamine oxidation were measured in lymphocytes, which suggests that an aminotransferase reaction(s) (probably aspartate aminotransferase) is important in the conversion of glutamate into oxoglutarate rather than glutamate dehydrogenase, and that the maximum activity of glutaminase is markedly in excess of the rate of glutamine utilization by incubated lymphocytes. The activity of glutaminase is increased by both starvation and the local immunological challenge in vivo. This last finding suggests that metabolism of glutamine via glutaminase is important in proliferating lymphocytes.
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PMID:Maximum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone-body and glutamine utilization pathways in lymphocytes of the rat. 716 29

This study was prompted by our incomplete understanding of the mechanism responsible for the clinical benefits of pharmacological doses of thiamin in some patients with maple syrup urine disease (MSUD) and the question of whether thiamin diphosphate (TDP), a potent inhibitor of the activity of the protein kinase that phosphorylates and inactivates the isolated branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, affects the activity state of the complex. Rats were fed a chemically-defined diet containing graded levels of thiamin (0, 0.275, 0.55, 5.5, and 55 mg thiamin/kg diet). Maximal weight gain was attained over a 3-wk period only in rats fed diets with 5.5 and 55 mg thiamin/kg. Feeding rats the thiamin-free diet for just 2 d caused loss of nearly half of the TDP from liver mitochondria. Three more days caused over 70% loss, an additional 3 wk, over 90%. Starvation for 2 d had no effect, suggesting a mechanism for conservation of TDP in this nutritional state. Mitochondrial TDP was higher in rats fed pharmacological amounts of thiamin (55 mg thiamin/kg diet) than in rats fed adequate thiamin for maximal growth. Varying dietary thiamin had marked but opposite effects on the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH) and BCKDH. Thiamin deficiency decreased alpha-KGDH activity, increased BCKDH activity, and increased the proportion of BCKDH in the active, dephosphorylated, state. Excess dietary thiamin had the opposite effects. TDP appears to be more tightly associated with alpha-KGDH than BCKDH in thiamin-deficient rats, perhaps denoting retention of alpha-KGDH activity at the expense of BCKDH activity. Thus, thiamin deficiency and excess cause large changes in mitochondrial TDP levels that have a major influence on the activities of the keto acid dehydrogenase complexes.
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PMID:Dietary thiamin level influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver. 1008 68

The yeast LPD1 gene encoding lipoamide dehydrogenase is subject to the general control of amino acid biosynthesis mediated by the GCN4 transcription factor. This is striking in that it demonstrates that GCN4-mediated regulation extends much farther upstream than simply to the direct pathways for amino acid and purine biosynthesis. In yeast, lipoamide dehydrogenase functions in at least three multienzyme complexes: pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase (which function in the entry of pyruvate into, and metabolism via, the citric acid cycle) and glycine decarboxylase. When wild-type cells were shifted from growth on amino acid-rich to amino acid-deficient medium, the expression of lipoamide dehydrogenase was induced approx. 2-fold. In a similar experiment no such induction was observed in isogenic gcn4 mutant cells. Northern analysis indicated that amino acid starvation affected levels of the LPD1 transcript. In the upstream region of LPD1 are three matches to the consensus for control mediated by GCN4. Directed mutagenesis of each site, and of all combinations of sites, suggests that only one site might be important for the general control response under the conditions tested. Gel-retardation analysis with GCN4 protein synthesized in vitro has indicated that GCN4 can bind in vitro to at least two of the consensus motifs.
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PMID:Transcription factor GCN4 for control of amino acid biosynthesis also regulates the expression of the gene for lipoamide dehydrogenase. 1035 73

An arbitrary-primed RNA PCR differential display strategy was used to identify midgut genes of the reduviid bug Triatoma infestans that were differentially expressed after a blood meal. From interesting bands, 33 distinct cDNAs were cloned and sequenced. Although many had long open reading frames, most of the transcripts were unrelated to any other sequences in any databases. Only 14 Triatoma sequences had strong homologies to those from other organisms, including genes encoding for 2-oxoglutarate dehydrogenase, CAD protein, NADH-ubiquinone-oxoreductase, epidermal growth factor, plectin, aminopeptidase, heat-shock-related 70-kDa protein, golgin, mitochondrial carrier protein and high-density lipoprotein. RT-PCR was used to demonstrate constitutive expression in four of five of these sequences. Northern hybridisation was difficult due to the very low expression levels of most of the genes. However, a gene-fragment highly homologous to a heat-shock-related 70-kDa protein was strongly expressed in starved bugs, down-regulated after feeding and again expressed later, suggesting a role for a heat-shock protein in starvation survival.
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PMID:Differential display of mRNAs associated with blood feeding in the midgut of the bloodsucking bug, Triatoma infestans. 1244 50

The response to iron limitation of the Gram-positive soil bacterium Corynebacterium glutamicum was analyzed with respect to secreted metabolites, the transcriptome, and the proteome. During growth in glucose minimal medium, iron limitation caused a shift from lactate to pyruvate as the major secreted organic acid complemented by l-alanine and 2-oxoglutarate. Transcriptome and proteome analyses revealed that a pronounced iron starvation response governed by the transcriptional regulators DtxR and RipA was detectable in the late, but not in the early, exponential-growth phase. A link between iron starvation and thiamine pyrophosphate (TPP) biosynthesis was uncovered by the strong upregulation of thiC As phosphomethylpyrimidine synthase (ThiC) contains an iron-sulfur cluster, limiting activities of the TPP-dependent pyruvate-2-oxoglutarate dehydrogenase supercomplex probably cause the excretion of pyruvate and 2-oxoglutarate. In line with this explanation, thiamine supplementation could strongly diminish the secretion of these acids. The upregulation of thiC and other genes involved in thiamine biosynthesis and transport is presumably due to TPP riboswitches present at the 5' end of the corresponding operons. The results obtained in this study provide new insights into iron homeostasis in C. glutamicum and demonstrate that the metabolic consequences of iron limitation can be due to the iron dependency of coenzyme biosynthesis.IMPORTANCE Iron is an essential element for most organisms but causes problems due to poor solubility under oxic conditions and due to toxicity by catalyzing the formation of reactive oxygen species (ROS). Therefore, bacteria have evolved complex regulatory networks for iron homeostasis aiming at a sufficient iron supply while minimizing ROS formation. In our study, the responses of the actinobacterium Corynebacterium glutamicum to iron limitation were analyzed, resulting in a detailed view on the processes involved in iron homeostasis in this model organism. In particular, we provide evidence that iron limitation causes TPP deficiency, presumably due to insufficient activity of the iron-dependent phosphomethylpyrimidine synthase (ThiC). TPP deficiency was deduced from the upregulation of genes controlled by a TPP riboswitch and secretion of metabolites caused by insufficient activity of the TPP-dependent enzymes pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase. To our knowledge, the link between iron starvation and thiamine synthesis has not been elaborated previously.
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PMID:The Iron Deficiency Response of Corynebacterium glutamicum and a Link to Thiamine Biosynthesis. 3214 5