Gene/Protein Disease Symptom Drug Enzyme Compound
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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

The fructose 2,6-bisphosphate (Fru-2,6-P2) content and intracellular concentration of lactating mammary gland was measured in fed, starved and re-fed rats. There was little or no change on starvation, and about 1.5-fold rise on re-feeding, contrasting with estimated glycolytic changes of about 10-fold. The 6-phosphofructokinase (PFK-1) activity of mammary extracts was highly sensitive to added Fru-2,6-P2 under all conditions examined, and appeared to approach saturation at physiological concentrations of this effector. The activity of mammary PFK-1 measured under optimal and 'physiological' conditions suggested that this enzyme operates in vivo at about 24% of maximal rate, and is likely to be an important rate-limiting factor in mammary glycolysis.
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PMID:Role of fructose 2,6-bisphosphate in mammary gland of fed, starved and re-fed lactating rats. 293 37

Seven cytoplasmic enzyme activities were measured in extracts of mononuclear leukocytes (lymphocytes plus monocytes) obtained from 19 type II diabetic humans and 10 healthy control subjects. 6-Phosphofructokinase activity was significantly decreased in cell extracts from diabetics, while other enzyme activities were similar in diabetics and controls. Since the effects of starvation on enzyme activities are sometimes similar to the effects of diabetes, the studies were repeated in 5 control subjects after a 2-day fast. This short period of starvation did not mimic the effect of diabetes on 6-phosphofructokinase activity. The decreased enzyme activity was not correlated with percent specific insulin binding to monocytes in the same cell preparations nor to clinical variables such as obesity or the broad range of fasting plasma glucose values encountered among the diabetics. We conclude that 6-phosphofructokinase activity in mononuclear leukocytes, as in other tissues, may be a marker for a postreceptor lesion associated with the insulin resistance found in type II diabetes mellitus.
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PMID:Impaired 6-phosphofructokinase activity in mononuclear leukocytes from patients with type II diabetes mellitus. 295 96

In general, the activities of enzymes in brown adipose tissue (BAT) are more similar to those in white adipose tissue than those in liver. Thus the activities of the glycolytic enzymes hexokinase and 6-phosphofructokinase are high but those of glucose 6-phosphatase and fructose bisphosphatase are non-detectable in the two adipose tissues. The activity of HMG-CoA synthase was non-detectable in BAT indicating that this tissue, unlike liver, cannot produce ketone bodies from fatty acid oxidation but, since the tissue possesses a high activity of HMG-CoA lyase, it might produce ketone bodies from leucine catabolism. The findings suggest that 'metabolically' brown adipose tissue can be classified better as an adipose tissue than as a peripheral liver. A high activity of 3-oxoacid CoA transferase but a non-detectable activity of 3-hydroxybutyrate dehydrogenase suggests that BAT can utilise acetoacetate but not 3-hydroxybutyrate for heat generation during cold exposure plus starvation.
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PMID:Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat. 374 27

In incubated colonocytes isolated from rat colons, the rates of utilization O2, glucose or glutamine were linear with respect to time for over 30 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 30 min. Glutamine, n-butyrate or ketone bodies were the only substrates that caused increases in O2 consumption by isolated incubated colonocytes. The maximum activity of hexokinase in colonic mucosa is similar to that of 6-phosphofructokinase. Starvation of the donor animal decreased the activities of hexokinase and 6-phosphofructokinase, whereas it increased those of glucose-6-phosphatase and fructose-bisphosphatase. Isolated incubated colonocytes utilized glucose at about 6.8 mumol/min per g dry wt., with lactate accounting for 83% of glucose removed. These rates were not affected by the addition of glutamine, acetoacetate or n-butyrate, and starvation of the donor animal. Isolated incubated colonocytes utilized glutamine at about 5.5 mumol/min per g dry wt., which is about 21% of the maximum activity of glutaminase. The major end-products of glutamine metabolism were glutamate, aspartate, alanine and ammonia. Starvation of the donor animal decreased the rate of glutamine utilization by colonocytes, which is accompanied by a decrease in glutamate formation and in the maximum activity of glutaminase. Isolated incubated colonocytes utilized acetoacetate at about 3.5 mumol/min per g dry wt. This rate was not markedly affected by addition of glucose or by starvation of the donor animal. When colonocytes were incubated with n-butyrate, both acetoacetate and 3-hydroxybutyrate were formed, with the latter accounting for only about 19% of total ketones produced.
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PMID:Fuel utilization in colonocytes of the rat. 407 34

The reason for the failure of early-stage mouse embryos to grow on glucose alone was investigated by measurement of glucose-6-phosphate, fructose-1,6-bisphosphate plus triose phosphates, citrate, and malate in individual embryos during starvation and refeeding with glucose or glucose plus pyruvate. The results indicate a block at the 6-phosphofructokinase (EC 2.7.1.11) step at early stages, which is later removed. Although there seems to be no early difficulty in phosphorylation of glucose, maximum glucose-6-phosphate levels (and probably fructose-6-phosphate levels) are much lower at early stages than at later stages. The increase in fructose-6-phosphate with age may be the major cause of the increase in 6-phosphofructokinase activity. Unusually high citrate levels at all ages may help to keep this enzyme strongly inhibited until the increase in fructose-6-phosphate occurs. The changes in metabolite levels also indicate an early defect in mobilization of glycogen and a probably less important defect in the citrate cycle.
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PMID:The explanation for the blockade of glycolysis in early mouse embryos. 427 92

Isolated incubated lymphocytes utilized acetoacetate, 3-hydroxybutyrate or oleate at about 0.5 mumol/min per g dry wt. These rates were not markedly affected by concanavalin A or by starvation of the donor animal. When ketone bodies replaced glucose in the culture medium, they could not support lymphocyte proliferation when cells were cultured for 48 h. Addition of oleate (0.5 mM) to isolated lymphocytes increased the rate of O2 consumption markedly, suggesting that it could contribute about 30% to O2 consumption. The rate of oleate uptake and the stimulated rate of O2 consumption were maximal at 0.5 M-oleate; this is in contrast with the effect in some other tissues, in which the rate of fatty acid oxidation is linear with concentration up to about 2 mM. Since the normal plasma concentration of fatty acid in the fed state is about 0.5 mM, this suggests that lymphocytes can utilize fatty acids at a maximal rate in the fed state. Ketone bodies or oleate decreased the rate of glucose utilization by incubated lymphocytes; ketone bodies decreased the rate of pyruvate oxidation and increased the intracellular concentration of hexose monophosphate and citrate, suggesting that 6-phosphofructokinase is inhibited by citrate, and hexokinase by glucose 6-phosphate. These effects may be important not so much in conserving glucose in the whole animal but in maintaining the concentrations of glycolytic intermediates necessary for biosynthetic processes during proliferation.
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PMID:Metabolism of ketone bodies, oleate and glucose in lymphocytes of the rat. 646 15

The metabolism of glutamine in resting and concanavalin-A-stimulated lymphocytes was investigated. In incubated lymphocytes isolated from rat mesenteric lymph nodes, the rates of oxygen and glutamine utilization and that of aspartate production were approximately linear with respect to time for 60 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 90 min. The major end products of glutamine metabolism were glutamate, aspartate and ammonia: the carbon from glutamine may contribute about 30% to respiration. When both glucose and glutamine were presented to the cells, the rates of utilization of both substances increased. Evidence was obtained that the stimulation of glycolysis by glutamine could be due, in part, to an activation of 6-phosphofructokinase. Starvation of the donor animal increased the rate of glutamine utilization. The phosphoenolpyruvate carboxykinase inhibitor mercaptopicolinate decreased the rate of glutamine utilization by 28%; the rates of accumulation of glutamate and ammonia were decreased, whereas those of lactate, aspartate and malate were increased. The mitogen concanavalin A increased the rate of glutamine utilization (by about 51%). The rate of [3H]thymidine incorporation into DNA caused by concanavalin A in cultured lymphocytes was very low in the absence of glutamine; it was increased about 4-fold at 1 microM-glutamine and was maximal at 0.3 mM-glutamine; neither other amino acids nor ammonia could replace glutamine.
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PMID:Glutamine metabolism in lymphocytes of the rat. 688 97

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

Few p53 regulators participate in selective control of p53-mediated cellular metabolism. How p53-mediated aerobic and glycolytic pathways are negatively regulated remains largely unclear. Here, we identified two KRAB-type zinc-finger proteins, PITA (p53 inhibitor of TIGAR activation) and PISA (p53 inhibitor of SCO2 activation), as selective regulators of p53 in metabolic control. PITA and PISA interact with p53 and specifically suppress transcription of the glycolysis regulator TIGAR and the oxidation phosphorylation regulator SCO2, respectively. Importantly, PITA transgenic mice exhibited increased 6-phosphofructokinase 1 (PFK1) activity and an elevated glycolytic rate, whereas PISA transgenic mice had decreased cytochrome c oxidase activity and reduced mitochondrial respiration. In response to glucose starvation, PITA dissociates from p53, resulting in activation of p53 and induction of TIGAR, which inhibited aerobic glycolysis. Prolonged starvation leads to PISA dissociation from p53 and induction of SCO2 and p53-promoted mitochondrial respiration. The dynamic regulation of PITA and PISA upon metabolic stress is dependent on ATM kinase-mediated phosphorylation of PITA and PISA. Furthermore, in human colorectal cancers, the elevated expression of PITA and PISA correlates with cancer progression. Depletion of PITA or PISA in colorectal cancer cells reduced the cell proliferation, migration and invasion. These results identify PITA and PISA as selective regulators of p53-mediated glycolysis and mitochondrial respiration and provide novel insights into the role of p53 network in cell metabolic control.
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PMID:KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration. 2957 87


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