Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of endotoxin on the activation of phosphoenolpyruvate carboxykinase by tryptophan was studied.
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PMID:Effect of endotoxin on the activation of phosphoenolpyruvate carboxykinase by tryptophan. 456 55

1. The administration of l-tryptophan to fed rats produces a twofold increase in hepatic phosphopyruvate carboxylase activity that represents a comparable increase in enzyme protein. With specific antibody against the enzyme we have shown that the increase in phosphopyruvate carboxylase is partially mediated via an actinomycin D-sensitive increase in enzyme synthesis. 2. In starved animals tryptophan increases the enzyme activity without any change in the relative rate of phosphopyruvate carboxylase synthesis. In this condition degradation of the enzyme is retarded by tryptophan by a mechanism that is not prevented by cycloheximide.
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PMID:Phosphopyruvate carboxylase induction by L-tryptophan. Effects on synthesis and degradation of the enzyme. 477 95

The enzyme phosphoenolpyruvate carboxykinase has been purified from chicken liver mitochondria. This purification includes a pseudo-affinity column step utilizing Sepharose 4B-blue dextran which binds the enzyme. The enzyme elutes with ITP to yield protein which is greater than 98% pure. The enzyme has Mr = 75,400 +/- 200 estimated by high speed sedimentation equilibrium and 70,500 +/- 500 estimated by reduced sodium dodecyl sulfate-polyacrylamide gels. The enzyme is abnormally retarded on molecular exclusion resins yielding low apparent molecular weight values. The amino acid analysis indicates that the enzyme has a high proline content and a high tryptophan content and contains 9 mol of cysteine/mol of enzyme. No disulfide bonds were detected. The extinction coefficient (epsilon 1% 280 = 16.5 +/- 0.1) reflects the high tryptophan content. The Svedberg coefficient (s20,w = 4.63 +/- 0.03 S) is consistent with a globular protein of Mr = 70,500-75,400. The activation of the enzyme was investigated by steady state kinetics. The carboxylation reaction has an activation energy of 17.6 kcal/mol. There is no requirement of a monovalent cation for activity. A thiol is necessary for maximal activity, although apparently not to reduce disulfide bonds within the enzyme. Incubation with dithiothreitol stabilizes enzymatic activity but beta-mercaptoethanol facilitates loss of activity. The kinetics of activation by Mn2+ was performed. The Ks value for phosphoenolpyruvate (300 microM) decreases to an apparent Km of 67 microM with increasing concentrations of Mn2+. The concentration of Mn2+ does not affect the interaction of HCO-3 with the enzyme, however. Analysis of data in terms of free IDP indicates that increasing Mn2+ decreases the Km of IDP but analysis as MnIDP indicates the Km,app of MnIDP is independent of the Mn2+ concentration. The enzyme interacts with Mn2+ with a KA = 67 microM and the Km,app decreases to a value of 8 microM with saturating substrates. The substrate analogue (Z)-3-fluorophosphoenolpyruvate is a good substrate for the reaction (Km = 30 microM) with 27% Vmax compared to P-enolpyruvate (Km = 180 microM). Except for 3-bromophosphoenolpyruvate, other analogues have shown weak competitive or noncompetitive inhibition. Potential analogues of oxalacetate (succinate, citrate, isocitrate, malate, and alpha-ketoglutarate) all elicit weak (greater than 15 mM) inhibition.
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PMID:The purification, characterization, and activation of phosphoenolpyruvate carboxykinase from chicken liver mitochondria. 706 3

The levels of quinolinic acid in liver and kidney and the gluconeogenic capacity in these tissues were determined in rats treated with tryptophan. The administration of this aminoacid produced a high increase in the hepatic quinolinic acid concentrations fed and 48 h. starved rats. On the contrary, only slight variations in the concentrations of renal quinolinic acid were observed. The highest value raised in these conditions was three times lower than Ki of the quinolinic acid for the phosphoenolpyruvate carboxykinase. These results suggest that tryptophan administration originates a selective inhibition of hepatic gluconeogenesis.
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PMID:[Selective inhibition of hepatic gluconeogenesis gy tryptophan administration]. 712 77

The mechanisms whereby tryptophan administration leads to hypoglycaemia in some groups of rats but not others have been investigated. Animals insensitive to tryptophan are rendered responsive by adrenalectomy. This effect is reversed by steroid replacement. Turnover studies with [2-3H]glucose show that hypoglycaemia in sensitive animals is associated with a decrease in glucose synthesis. Tryptophan administration causes a marked and sustained increase in plasma glucagon concentrations in all animals. The locus of the inhibition of gluconeogenesis in tryptophan-sensitive animals is the reaction catalysed by phosphoenolpyruvate carboxykinase. The sensitivities to tryptophan of gluconeogenesis in isolated hepatocytes from normal and adrenalectomized animals were similar. Cells from chronically streptozotocin-diabetic animals required higher concentrations of the amino acid for the same effect. These results are discussed in relation to previous discrepancies in the literature, and a unifying hypothesis for tryptophan-induced hypoglycaemia is proposed.
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PMID:Factors affecting tryptophan-induced hypoglycaemia in rats. 718 38

1. Hepatic fatty acid synthesis, measured in vivo using 3H2O, was increased by a single dose of L-tryptophan (50 mg/kg body-weight) to both fed and fasted rats and by a supplement of tryptophan to the diet (2.5 g/kg diet for 7 d) when the rats were killed midway through the feeding period. 2. Additional dietary tryptophan was hypotriglyceridaemic in normal rats but exacerbated the hypertriglyceridaemia in rats when lipoprotein clearance was impaired 24 h after an injection of Triton WR 1339 (Chromatography Services Co., Birkenhead, Cheshire). 3. The effects of tryptophan on hepatic fatty acid synthesis and the concentration of serum triglyceride were not directly related to the action of the amino acid on gluconeogenesis. A lack of correlation between inhibition of gluconeogenesis and enhancement of lipogenesis was confirmed using mercaptopicolinic acid, a specific inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). 4. DL-Tryptophan itself did not provide a significant contribution of substrate to the total rate of lipogenesis. Other possible explanations for the activity of tryptophan noted in the present experiments are discussed. 5. In conclusion, moderate intakes of tryptophan affect fatty acid and triglyceride metabolism under physiological conditions and it is proposed that the amino acid may be involved in the control of lipid metabolism in a variety of metabolic states.
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PMID:Tryptophan and the control of triglyceride and carbohydrate metabolism in the rat. 737 42

1. Phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) from tryptophan-treated normal rats, when assayed immediately after preparation is not activated by Fe2+ but is inhibited 65% by 2.0 mM quinolinate whether or not Fe2+ is present. As time of storage increases, the enzyme's sensitivity to Fe2+ activation returns as does the ability of quinolinate to more effectively inhibit the Fe2+-activated enzyme. 2. Phosphoenolpyruvate carboxykinase from NaCl- and tryptophan-treated diabetic rats is activated about 2-fold by 20 microM Fe2+. Quinolinate (2.0 mM) inhibits the Fe2+-activated enzyme 65% compared to 20% inhibition of the non-Fe2+-activated enzyme. In these respects, the enzyme from NaCl- and tryptophan-treated diabetic rats acts in vitro just like the enzyme from NaCl-treated normal rats and unlike the enzyme from tryptophan-treated normal rats. Thus, the inability of tryptophan and quinolinate to inhibit gluconeogenesis and to alter the assayable activity of phosphoenolpyruvate carboxykinase from diabetic rats in vivo is inconsistent with quinolinate's ability to inhibit the enzyme in vitro. 3. Quinolinate's inhibition of phosphoenolpyruvate carboxykinase from NaCl, tryptoiphan-treated normal and diabetic rats is of a 'mixed' nature. 4. Hepatic cytosolic phosphoenolpyruvate carboxykinases from fasted normal guinea pigs, pigeons, and rabbits are activated 2-3-fold by Fe2+ and inhibition by quinolinate in the presence of Fe2+ ranges from 65-75% compared to no inhibition without Fe2+. Mitochondrial carboxykinases from these three species are only activated 20-30% by Fe2+, although quinolinate, which is ineffective as an inhibitor in the absence of Fe2+, inhibits the enzymes 40-50% in the presence of Fe2+.
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PMID:Responses of hepatic phosphoenolypyruvate carboxykinase activities from normal and diabetic rats to quinolinate inhibition and ferrous ion activation. 739

Despite the marked changes that crustacean muscle undergoes during the molt cycle, pyruvate kinase is present as the same form throughout the molt cycle. This pyruvate kinase was subject to feed-forward activation by fructose-1, 6 bisphosphate (FBP) as well as feed-back inhibition by MgATP. The enzyme showed a high affinity for phosphoenolpyruvate (Km = 0.1 mM) but showed no cooperativity in substrate binding. The addition of 0.05 mM FBP reduced the PEP Km to 0.05 mM. MgATP inhibition showed a Ki of 1.8 mM versus PEP. The inhibition due to MgATP could be reversed by FBP. Various other compounds inhibited the enzyme, including citrate, alpha-ketoglutarate, tryptophan, and malate, although at rather high levels. Measurements of the reversal of this pyruvate kinase, taken together with the low levels of phosphoenolpyruvate carboxykinase and pyruvate carboxylase, predict only minimal levels of gluconeogenic flux in crustacean muscle.
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PMID:Catalytic and regulatory properties of muscle pyruvate kinase from Cancer magister. 746 68

The hypothesis tested in this experiment is that effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) show identical dose-responses after subchronic as after acute exposure when the dose is corrected for toxicokinetics. Groups of male Sprague-Dawley (S-D) rats were administered orally a total dose of 0, 0.2, 2.3, 11.5, 35, 70 or 115 micrograms/kg of TCDD over a period of 10 weeks at 4 ml/kg of vehicle. Body weight was recorded weekly. One week after the last dose of TCDD one half of the rats was killed and tryptophan 2,3-dioxygenase (TdO), 7-ethoxyresorufin-O-deethylase (EROD) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in livers, whereas tryptophan and total T4 (TT4) were determined in serum. The results show that the dose-response for decreased TdO and PEPCK activity and elevated serum tryptophan levels are similar if not the same as the dose-response for subchronic retardation of body weight increase. They also demonstrate that the dose-responses for the induction of EROD activity and the reduction of serum TT4 occurred at much lower doses than those for decreased TdO and PEPCK activities or elevated tryptophan levels and mortality. After a 6-week recovery period, PEPCK and TdO activities in liver as well as tryptophan in serum returned to near control values, whereas EROD activity and serum TT4 still displayed a dose-dependent induction and reduction, respectively, albeit both shifted to the right in accordance with toxicokinetics. These data support the notion that subchronic dose-responses of TCDD are similar to acute dose-responses when corrected for toxicokinetics and that at least some TCDD-induced effects are reversible also in accordance with toxicokinetics.
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PMID:Subchronic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and their reversibility in male Sprague-Dawley rats. 771 79

The aim of this study was to examine the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin, (TCDD) in a rat strain other than the Sprague-Dawley (S-D) rat, for which most of our data have been generated thus far. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 micrograms/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T4 (TT4) and total T3 (TT3) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), gamma-glutamyl transpeptidase (gamma-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic gamma-GT activity was also dose-dependently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat. 771 64


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