Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.49 (phosphoenolpyruvate carboxykinase)
 4,654 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic responses associated with prolonged fasting and subsequent refeeding of pigs were investigated. Fasting for 14 or 28 days produced significant increases in serum levels of alanine, aspartic and glutamic acid in the three branched-chain amino acids. Glycine, serine and lysine levels were elevated after 28 days of fasting while the levels of histidine, methionine, threonine and phenylalanine were reduced. Fasting markedly stimulated hepatic and renal gluconeogenesis and the activity of the urea cycle enzymes. Fatty acid synthesis and glucose oxidation were virtually abolished in hepatic and adipose tissue in pigs subjected to a 14- or 28-day fast. After the first day of refeeding, the levels of amino acids returned to the control values. The activity of the hepatic urea cycle enzymes, fructose-1,6-diphosphatase and phosphoenolpyruvate carboxykinase remained elevated after the first day of refeeding but returned to the control levels thereafter. The activity of hepatic glucose-6-phosphate dehydrogenase, malic dehydrogenase and acetyl CoA carboxylase were slightly enhanced in pigs refed for 4 and 8 days. The activity of these enzymes in adipose tissue was enhanced 8 days after refeeding. Hepatic synthesis of fatty acids from glucose was slightly stimulated in refed pigs on days 4 and 8 but returned to control values on day 16. Refeeding did not enhance glucose incorporation into fatty acids in adipose tissue above the values observed in fed controls.
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PMID:Metabolic responses to prolonged fasting and subsequent refeeding in the pig. 55 35

This study examines the role of impaired gluconeogenesis in the pathogenesis of neonatal hypoglycemia in intrauterine growth retardation (IUGR). IUGR was produced experimentally in eight pregnant rats by ligation of uterine arteries at the 17th day of gestation. Delivery occurred spontaneously at term. Sham operations were performed in five pregnant rats at the same gestational age and the fetuses delivered at term served as controls. The body weights of newborn rats with IUGR were significantly lower than the controls (5.32 +/- 0.12 vs. 6.22 +/- 0.06 g, mean +/- SE, P less than 0.001). The fetal liver weights were also significantly smaller in IUGR than in the control animals (0.224 +/- 0.14 vs. 0.340 +/- 0.12 g, P less than 0.001). The activity of phosphoenolpyruvate carboxykinase (PEPCK) (the rate-limiting enzyme of gluconeogenesis) in liver cytosols was significantly lower in rats with IUGR (0.06 +/- 0.01 vs. 0.11 +/- 0.02 microM phosphoenolpyruvate/g liver/min when compared with controls (P less than 0.05). A direct relationship between this enzyme and the birth weight was observed, suggesting a close relationship between intrauterine nutrition and the status of gluconeogenesis. The blood glucose level was also lower in growth-retarted fetuses (36.6 +/- 4.7 vs. 69.6 +/- 4.3 mg/dl, p less than 0.001) when compared with controls. The data suggest that gluconeogenesis is impaired in IUGR and is partly responsible for the increase in the incidence of neonatal hypoglycemia in this group of subjects.
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PMID:Phosphoenolpyruvate carboxykinase in experimental intrauterine growth retardation in rats. 58 64

Clofibrate was administered in the diet (0.3% w/w) for varying periods of time to normal rats. Rats were killed by decapitation and several biochemical measurements were made. Clofibrate lowered serum levels of cholesterol and triglyceride and produced a kidney hypertrophy; these effects were maximal after 3 days of feeding and persisted for 21 days. Serum clofibric acid levels were highest on the 3rd day and decreased to maintenance levels by the 7th day. Clofibrate markedly increased the activities of glucose 6-phosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase in kidney cortex and the synthesis of glucose from glutamate, lactate, pyruvate, glycerol and malate by kidney cortex slices. Clofibrate treatment did not affect blood pH or bicarbonate levels. It is concluded that clofibrate enhances renal gluconeogenesis in the rat and that the effect is not caused by altering acid-base balance.
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PMID:Renal gluconeogenesis in clofibrate-treated rats. 63 72

The metabolism of proline was studied in liver cells isolated from starved rats. The following observations were made. 1. Consumption of proline could be largely accounted for by production of glucose, urea, glutamate and glutamine. 2. At least 50% of the total consumption of oxygen was used for proline catabolism. 3. Ureogenesis and gluconeogenesis from proline could be stimulated by partial uncoupling of oxidative phosphorylation. 4. Addition of ethanol had little effect on either proline uptake or oxygen consumption, but strongly inhibited the production of both urea and glucose and caused further accumulation of glutamate and lactate. Accumulation of glutamine was not affected by ethanol. 5. The effects of ethanol could be overcome by partial uncoupling of oxidative phosphorylation. 6. The apparent K(m) values of argininosuccinate synthetase (EC 6.3.4.5) for aspartate and citrulline in the intact hepatocyte are higher than those reported for the isolated enzyme. 7. 3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32), greatly enhanced cytosolic aspartate accumulation during proline metabolism, but inhibited urea synthesis. 8. It is concluded that when proline is provided as a source of nitrogen to liver cells, production of ammonia by oxidative deamination of glutamate is inhibited by the highly reduced state of the nicotinamide nucleotides within the mitochondria. 9. Conversion of proline into glucose and urea is a net-energy-yielding process, and the high state of reduction of the nicotinamide nucleotides is presumably maintained by a high phosphorylation potential. Thus when proline is present as sole substrate, the further oxidation of glutamate by glutamate dehydrogenase (EC 1.4.1.3) is limited by the rate of energy expenditure of the cell.
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PMID:Prolone metabolism in isolated rat liver cells. 64 9

Chronic (6 days) hyperinsulinaemia in young rats produced lower blood glucose concentrations and augmented body- and liver-weight gain. The insulin-treated rats had increased hepatic activities of citrate-cleavage enzyme, 'malic' enzyme and high-substrate (6.6 mM-phosphoenolpyruvate) pyruvate kinase, and decreased glucose 6-phosphatase. There were no changes in activities of phosphoenolpyruvate carboxykinase, phosphofructokinase, low-substrate (1.3 mM-phosphoenolpyruvate) pyruvate kinase, glucokinase and hexokinase.
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PMID:Effects of chronic hyperinsulinaemia on hepatic enzymes involved in lipogenesis and carbohydrate metabolism in the young rat. 66 50

1. The effects of atractyloside and carboxyatractyloside (between 5 and 40mum) on O(2) uptake, glucose synthesis, urea synthesis, the adenine nucleotide content and the intracellular K(+) concentration were measured in isolated hepatocytes. 2. Urea synthesis was much less inhibited than glucose synthesis by both atractylosides. Measurements of intermediary metabolites of carbohydrate metabolism in freeze-clamped liver after injection of atractyloside into rats indicate that inhibition of gluconeogenesis is due to interference at the cytosolic reactions requiring ATP (phosphoenolpyruvate carboxykinase and 3-phosphoglycerate kinase). 3. The decrease in [ATP]/[ADP]x[P(i)] after addition of atractyloside or carboxyatractyloside was restricted to the cytosol. 4. Dihydroxyacetone can be converted either into glucose with the consumption of 2mol of ATP (per mol of glucose) or into lactate with the production of 2mol of ATP. In the presence of high concentrations of atractyloside and carboxyatractyloside more ATP was produced than was used for the synthesis of glucose from dihydroxyacetone, probably for the maintenance of intracellular [K(+)]. 5. When the rates of respiration were altered by changing substrates, the degrees of inhibition of respiration and translocation by a given concentration of the atractylosides were the same, whereas at a given concentration of HCN the degree of inhibition was high at higher initial rates, and low at lower initial rates. 6. Inhibition of a complex series of reactions by atractyloside does not necessarily indicate that the translocator is a rate-limiting step in that sequence as Th. P. M. Akerboom, H. Bookelman & J. M. Tager [(1977) FEBS. Lett.74, 50-54] assume. This point is discussed.
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PMID:Is the adenine nucleotide translocator rate-limiting for oxidative phosphorylation? 66 51

Experiments were carried out on rats to evaluate the possible regulatory roles of renal glutaminase activity, mitochondrial permeability to glutamine, phosphoenolpyruvate carboxykinase activity and systemic acid-base changes in the control of renal ammonia (NH(3) plus NH(4) (+)) production. Acidosis was induced by drinking NH(4)Cl solution ad libitum. A pronounced metabolic acidosis without respiratory compensation [pH=7.25; HCO(3) (-)=16.9mequiv./litre; pCO(2)=40.7mmHg (5.41kPa)] was evident for the first 2 days, but thereafter acid-base status returned towards normal. This improvement in acid-base status was accompanied by the attainment of maximal rates of ammonia excretion (onset phase) after about 2 days. A steady rate of ammonia excretion was then maintained (plateau phase) until the rats were supplied with tap water in place of the NH(4)Cl solution, whereupon pCO(2) and HCO(3) (-) became elevated [55.4mmHg (7.37kPa) and 35.5mequiv./litre] and renal ammonia excretion returned to control values within 1 day (recovery phase). Renal arteriovenous differences for glutamine always paralleled rates of ammonia excretion. Phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase activities and the rate of glutamine metabolism (NH(3) production and O(2) consumption) by isolated kidney mitochondria all increased during the onset phase. The increases in glutaminase and in mitochondrial metabolism continued into the plateau phase, whereas the increase in the carboxykinase reached a plateau at the same time as did ammonia excretion. During the recovery phase a rapid decrease in carboxykinase activity accompanied the decrease in ammonia excretion, whereas glutaminase and mitochondrial glutamine metabolism in vitro remained elevated. The metabolism of glutamine by kidney-cortex slices (ammonia, glutamate and glucose production) paralleled the metabolism of glutamine in vivo during recovery, i.e. it returned to control values. The results indicate that the adaptations in mitochondrial glutamine metabolism must be regulated by extra-mitochondrial factors, since glutamine metabolism in vivo and in slices returns to control values during recovery, whereas the mitochondrial metabolism of glutamine remains elevated.
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PMID:Glutamine metabolism in the kidney during induction of, and recovery from, metabolic acidosis in the rat. 70 90

1. Glucose production from L-lactate was completely inhibited 24h after carbon tetrachloride treatment in liver from 48h-starved rats. The activities of phosphoenolpyruvate carboxykinase, fructose diphosphatase and glucose 6-phosphatase were decreased by this treatment in fed and starved rats, whereas lactate dehydrogenase activity was only decreased in fed animals. 2. The production of glucose by renal cortical slices from fed rats previously treated with carbon tetrachloride was enhanced when L-lactate, pyruvate and glutamine but not fructose were used as glucose precursors. Renal phosphoenolpyruvate carboxykinase activity was increased in this condition. 3. This increase was counteracted by cycloheximide or actinomycin D, suggesting that the effect was due to the synthesis de novo of the enzyme. 4. The pattern of hepatic gluconeogenic metabolites in treated animals was characterized by an increase in lactate, pyruvate, malate and citrate as well as a decrease in glucose 6-phosphate, suggesting an impairment of liver gluconeogenesis in vivo. 5. In contrast, the profile of renal metabolites suggested that gluconeogenesis was operative in the treated rats, as indicated by the marked increase in the content of phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate and glucose 6-phosphate. 6. It is postulated that renal gluconeogenesis could contribute to the maintenance of glycaemia in carbon tetrachloride-treated rats.
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PMID:Induction of rat kidney gluconeogenesis during acute liver intoxication by carbon tetrachloride. 70 98

1. Measurements have been made of the activities of enzymes of the glycolytic route, the pentose phosphate pathway, the tricarboxylic acid cycle and lipogenesis in liver and adipose tissue from genetically obese (fa/fa) rats and their lean litter mates (fa/ --). The effect of food restriction for a period of three weeks on the enzyme profile of liver and adipose tissue of the obese rat was also studied. 2. The most striking increases in enzyme activity in livers from obese rats were: (a) among enzymes of lipogenesis; ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthetase, malate dehydrogenase (decarboxylating) and cytoplasmic glycerolphosphate dehydrogenase; (b) within the pentose phosphate pathway; glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase; (c) within the glycolytic pathway; glucokinase, pyruvate kinase and lactate dehydrogenase. All of these enzymes showed a significant increase in activity on the basis of U/g liver and U/mg DNA. In adipose tissue all the enzymes of lipogenesis, of the glycolytic route, of the oxidative segment of the pentose phosphate pathway and of the tricarboxylic acid cycle were increased when expressed as U/2 fat pads or as U/mg DNA. 3. The restriction of the food intake of obese rats to that consumed by their lean litter mates for periods of three weeks did not produce the expected adaptive decrease in enzymes of lipogenesis; in adipose tissue, only ATP-citrate lyase and malate dehydrogenase (decarboxylating) showed a marked decrease; no significant change was found in adipose tissue or liver of the activities of acetyl-CoA carboxylase and fatty acid synthetase, when expressed on a cell basis (U/mg DNA). The non-oxidative enzymes of the pentose phosphate pathway and enzymes involved in glycerogenesis (pyruvate carboxylase, malate dehydrogenase and phosphoenolpyruvate carboxykinase) all increased in adipose tissue from limit-fed obese rats. 4. The rate of conversion of specifically labelled glucose to (14C)O2 and 14C-labelled lipid by pieces of adipose tissue and by liver slices was also measured. Insulin caused an increase in the conversion of (1-14C)glucose to (14C)O2 and 14C-labelled lipid in obese rats fed ad libitum, limit-fed rats and in their lean litter mates. 5. The results are discussed in relation to the raised insulin and hypothyroid state of the obese rat. The effect of this altered hormonal status on the activity of cyclic nucleotide phosphodiesterases and cellular levels of adenosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate in relation to the obese syndrome is considered.
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PMID:Adaptive responses of enzymes of carbohydrate and lipid metabolism to dietary alteration in genetically obese Zucker rats (fa/fa). 71 Mar 95

Administering 3-aminopicolinate to rats starved for 24h immediately initiated a progressive increase in blood glucose concentration. Hyperglycaemia was not the result of glycogenolysis, nor was it due to an inhibition of insulin release, since it caused marked hyperinsulinaemia. The rate of [6-(3)H]glucose disappearance from the blood of the intact rat was not altered by 3-aminopicolinate, indicating that it does not cause hyperglycaemia by inhibiting glucose utilization or by causing a redistribution of total body glucose. 3-Aminopicolinate increased the rate of fall in the specific radioactivity of blood [6-(3)H]-glucose, indicating dilution of the glucose pool by newly synthesized glucose. The rate of (14)C incorporation into blood glucose from [(14)C]alanine and [(14)C]lactate was increased 90 and 35% respectively, whereas that from [(14)C]glycerol and [(14)C]xylitol was either unaffected or slightly decreased by 3-aminopicolinate administration. Liver phosphoenolpyruvate of rats was increased to four to seven times the normal concentration 10min to 1h after injections of 50-300mg of 3-aminopicolinate/kg body wt. and the amounts of 2-phosphoglycerate and 3-phosphoglycerate were increased to three to four times normal. The high concentrations of liver phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate, as well as the enhancement of gluconeogenesis from lactate and alanine, but not from glycerol or xylitol, is compatible with an enhancement of gluconeogenesis at a step between pyruvate and the triose phosphates. After injections of 3-aminopicolinate, liver malate, citrate, aspartate, alanine, lactate and pyruvate were also increased, but to lesser extents than was phosphoenolpyruvate. The increases in some of these metabolites were approximated after an intravenous infusion of glucose, so their elevated concentration after 3-aminopicolinate administration could have been, in part, a consequence of the hyperglycaemia. The possibility is considered that 3-aminopicolinate stimulates gluconeogenesis in vivo by facilitating Fe(2+) activation of phosphoenolpyruvate carboxykinase as it does with the purified enzyme in vitro [MacDonald & Lardy (1978) J. Biol. Chem.253, 2300-2307]. In this effect 3-aminopicolinate may simulate the physiological role of the naturally occurring ferroactivator protein [Bentle & Lardy (1977) J. Biol. Chem.252, 1431-1440].
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PMID:Hyperglycaemic activity and metabolic effects of 3-aminopicolinic acid. 74 55


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