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)

1. In vitro glucose uptake and glycogen utilization by Hymenolepis microstoma decreased under high oxygen concentrations. 2. 5-Hydroxytryptamine did not stimulate in vitro glucose uptake but did increase glycogen utilizations by H. microstoma. 3. The reduced glucose uptake under high oxygen concentrations (21 and 95%) resulted in a reduction in excretory products. 4. 14CO2-incorporation studies confirmed that, under both 95% O2:5% CO2 and air-minus-CO2 (identical to 21% O2). CO2-fixation by phosphoenolpyruvate carboxykinase (EC 4.1.1.32) was inhibited. 5. The specific activity of hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40) was not stimulated by 5-HT. 6. The concentration of ATP required for optimal stimulation of phosphofructokinase activity was 0.67 mM. Activity was further significantly increased by the addition of cAMP and even greater by AMP.
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PMID:5-hydroxytryptamine, glucose uptake, glycogen utilization and carbon dioxide fixation in Hymenolepis microstoma (Cestoda). 681 65

The ratio of free ATP to free ADP in the mitochondrial matrix [( ATPf]/[ADPf]) has been measured in suspensions of isolated mitochondria under conditions of active phosphorylation of extramitochondrial ADP. These measurements utilized phosphoenolpyruvate carboxykinase which is present in the matrix of mitochondria from the livers of guinea pigs, chickens, and pigeons. Mitochondria isolated from these sources also contain nucleoside diphosphate kinase, malate dehydrogenase, and glutamate dehydrogenase or 3-OH-butyrate dehydrogenase. Together these enzymes catalyze the synthesis of phosphoenolpyruvate and CO2 from oxaloacetate with oxidative phosphorylation as an energy source. These reactions have been shown to be fully reversible in suspensions of mitochondria isolated from the above sources. With oxidative phosphorylation as the source of ATP, phosphoenolpyruvate was synthesized from malate and conversely addition of phosphoenolpyruvate, ADP, and CO2 led to synthesis of malate and ATP. The forward and reverse reactions were allowed to continue until the rate of change of metabolite concentrations was minimal and then the latter were measured. The intramitochondrial [Mg-ATPf]/[MgADPf] was calculated from the equilibrium constants for the reactions and the measured steady state concentrations of the metabolites in both the intra- and extramitochondrial spaces. The value of the intramitochondrial [MgATPf]/[MgADPf] was found to exceed the extramitochondrial value (adjusted to the same free Mg2+ concentration) by a factor (+/- S.E.) of 0.83 +/- 0.22 (n = 17) for the forward reaction and 1.81 +/- 0.54 (n = 11) for the reverse reaction. It is concluded that the adenine nucleotide translocase catalyzes electroneutral exchange of ATP for ADP and that this reaction does not contribute significantly to the energetics of mitochondrial oxidative phosphorylation.
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PMID:Evaluation of the relationship between the intra- and extramitochondrial [ATP]/[ADP] ratios using phosphoenolpyruvate carboxykinase. 688 88

The utilisation (conversion to CO2 and/or glucose) of a series of amino acids by isolated trout hepatocytes was investigated and compared to the utilisation of lactate and palmitate. In fed fish, several amino acids (alanine, serine, asparagine and glycine) and lactate produced CO2 at considerably higher rates than palmitate. During starvation plus exercise, the rate of CO2 production from palmitate increased while that from lactate and most of the amino acids decreased. Gluconeogenesis from amino acids in fed fish was lower than from lactate. Serine and asparagine were the most effective substrates; alanine gave lower rates of incorporation. During prolonged starvation plus exercise, the rates of gluconeogenesis from amino acids increased twofold and, simultaneously, there was a corresponding increase in phosphoenolpyruvate carboxykinase activity in liver. It is concluded that several amino acids (dietary or released from muscle protein) are potentially major oxidative substrates in trout. In addition, amino acids appear to have the capability to maintain supplies of glucose during a period of prolonged starvation and exercise. No evidence could be found to support the contention that alanine is the most important glucogenic amino acid.
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PMID:Amino acid utilisation in isolated hepatocytes from rainbow trout. 720 13

To study the interrelationships of phosphoenolpyruvate carboxykinase and glyceroneogenesis in adipose tissue, investigations with two effectors of the hepatic carboxykinase, Fe2+ and Mn2+, and two inhibitors of the enzyme and of gluconeogenesis in liver, quinolinic acid and 3-mercaptopicolinic acid, were carried out. Incubating adipose tissue cytosol with 30 microM Fe2+ or 100 microM Mn2+ prior to assaying for phosphoenolpyruvate carboxykinase activity doubled the enzyme activity. Inhibition of the enzyme by quinolinate alone was minimal. Adding 30 microM Fe2+ to the cytosol decreased the K0.5 (concentration that gives 50% inhibition) for quinolinate to 0.4 mM and the K0.5 for mercaptopicolinate from 200 to 14 microM. Activating the enzyme with 100 microM Mn2+ did not lower the K0.5 values and adding 500 microM Mn2+ to the cytosol completely interfered with the enhancement of inhibition induced by Fe2+. Each inhibitor interfered with 14C incorporation into glyceride glycerol from labeled pyruvate, alanine and lactate in suspensions of adipocytes. Adding 1 mM Mn2+ to the adipocyte suspension almost completely prevented the inhibition of pyruvate and alanine incorporation into glyceride glycerol, but adding the Mn2+ or 250 microM Fe2+ to the adipocytes in the absence of inhibitors did not enhance glyceride glycerol formation. Adding 250 microM Fe2+ to the adipocytes did not enhance inhibition of lipid synthesis by mercaptopicolinate or quinolinate. Mercaptopicolinate did not inhibit glyceride glycerol, fatty acid, total lipid or CO2 production from glucose. The lack of activation of glyceride glycerol synthesis by added Fe2+ or Mn2+, the lack of enhancement of pyridine carboxylate inhibition by Fe2+ and the interference with inhibition by Mn2+ are compatible with the idea that a transition metal ion similar to Fe2+, if not Fe2+ itself, is available to, or loosely bound to, the adipose tissue carboxykinase in vivo. Taken together with the results of previous work which showed ferroactivator (a cytosol protein necessary for Fe2+ activation of the carboxykinase) to be present in adipose tissue, the present results indicate that the control of the adipose tissue carboxykinase may be similar to the enzyme in liver. Fatty acid synthesis was also diminished by the inhibitors, albeit to a lesser extent than was glyceride glycerol formation. It is hypothesized that this was secondary to decreased esterification caused by the lack of glycerol 3-phosphate from inhibition of the carboxykinase. Decreased esterification would lead to a build-up of fatty acyl CoA which inhibits fatty acid synthesis.
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PMID:Inhibition of phosphoenolpyruvate carboxykinase, glyceroneogenesis and fatty acid synthesis in rat adipose tissue by quinolinate and 3-mercaptopicolinate. 721 68

Carbon isotope effects for the carbon atom arising from bicarbonate have been measured for the phosphoenolpyruvate carboxylase from maize. At pH 7.5, 25 degrees C, the isotope effect is K12/k13 = 1.0029 +/- 0.0005 in the presence of Mg2+. The isotope effect decreases with increasing pH, reaching a value of 0.9973 at pH 10.0. All these isotope effects are relative to HCO3(-) taken as the starting state. If CO2 is considered the starting state, the isotope effects are all inverse. These values suggest that the carboxylation of phosphoenolpyruvate occurs by way of a stepwise mechanism involving an enzyme-bound carboxyphosphate intermediate, with formation of the intermediate being the primary rate-determining step. Steady-state kinetics reveal that Vmax is independent of pH over the range pH 7.5-10.0 Vmax/Km (phosphoenolpyruvate) is bell shaped in the same interval. Two pKa values near 7 are observed; the first is attributed to ionization of the phosphate group of phosphoenolpyruvate and the second to an unidentified group on the enzyme. Activity of the enzyme also depends on protonation of a group on the enzyme with a pKa near 10. Several metal ions were tested as activators of phosphoenolpyruvate carboxylase. Under saturating conditions, Mg2+ and Mn2+ show equal activity but different carbon isotope effects. Co2+ has about half the activity of Mg2+ and shows an inverse carbon isotope effect.
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PMID:Kinetic and isotope effect studies of maize phosphoenolpyruvate carboxylase. 731 83

Male weanling rats were meal-fed (2 hours daily) on a vitamin B-6-deficient diet for 8 weeks; the controls were pair-fed. Vitamin B-6 deficiency led to the expected decreases in the activities of hepatic alanine and aspartate aminotransferases but did not influence those of glutamate dehydrogenase (EC 1.4.1.2), pyruvate carboxylase (EC 6.6.1.1), phosphoenolpyruvate carboxykinase (EC 4.1.1.32) and pyruvate kinase (EC 2.7.1.40). The ability of the deficient rats to incorporate 14C from labeled alanine into blood glucose and expired CO2 was diminished, but pyruvate-U-14C was utilized normally. The deficiency did not influence gluconeogenesis from glutamate or 2-oxoglutarate. Furthermore, the gluconeogenic potential of renal cortex slices incubated with pyruvate or 2-oxoglutarate was unaltered by the deficiency. These data suggest that the impairment of gluconeogenesis from amino acids in vitamin B-6 deficiency may be the consequence of diminished transamination prior to oxidative deamination.
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PMID:Gluconeogenesis in meal-fed, vitamin B-6-deficient rats. 735 97

Estradiol treatment of starving immature rainbow trout dramatically alters the metabolic performance of isolated hepatocytes. One and two weeks postimplantation with estradiol, the rate of de novo glucose synthesis from [14C]alanine is reduced fourfold from 0.4 mumol/g/hr to 0.1 mumol/g/hr, compared with vehicle-injected control fish. After 6 weeks, the rate of glucose production on a gram wet weight basis is identical in both treatment groups, but significantly larger (by 80%) in the estradiol-treated group than in the controls, if expressed normalized to the hepatosomatic index (HSI). Estradiol treatment caused preferential partitioning of alanine carbon into oxidative pathways away from gluconeogenesis, indicated by a significantly lower ratio of glucose production over CO2 production in hepatocytes isolated from estradiol-treated animals. Incorporation of [14C]alanine into acid-precipitable protein is significantly larger in the estradiol-treated group after 2 weeks, and also after 6 weeks, when normalized to the HSI, indicating that part of the protein synthesized in the estradiol-treated groups is vitellogenin. No differences were detected between estradiol-treated animals and control animals in the activities of enzymes associated with gluconeogenesis [phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase (FBPase)] and amino acid metabolism (alanine and aspartate aminotransferases) in the time course investigated (expressed on a wet weight basis). Activities normalized to the HSI are higher in fish implanted with estradiol compared with controls at 2 and 6 weeks. In keeping with the increased potential of hepatocytes for CO2 production from alanine, estradiol treatment doubled and tripled the maximum activity of pyruvate kinase 1 and 2 weeks postimplantation, respectively. Fish were fasted to avoid erratic feeding due to treatments. Superimposed on estradiol actions are effects of starvation: a fourfold increase in the rate of gluconeogenesis, a threefold increase in oxidative flux, and a fivefold increase in the activity of FBPase--all normalized to hepatocyte weight.
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PMID:Gluconeogenesis in hepatocytes of immature rainbow trout (Oncorhynchus mykiss): control by estradiol. 767 84

The results from the experiments performed with a mutant deficient in citrate synthase activity can be summarized as follows. (1) Totally blocking entry into the TCA cycle did not appreciably alter the cellular ATP yield. The unchanged yield suggests that for growth on abundant glucose, the sensitivity of ATP yield to TCA cycle flux is low. ATP production in the mutant is altered, in part, by modulating the relative amounts of formate and acetate produced. (2) The in vivo operation of pyruvate-formate lyase and malic enzyme corresponds to proposals developed from in vitro studies. Namely, pyruvate activates the former, and acetyl CoA inhibits the latter. Overall, the diversion of pyruvate to formate under aerobic conditions constitutes an adaptation of the mutant to the enzymatic lesion. The low alpha-ketoglutarate dehydrogenase flux estimated for the mutant indicates that the enzyme is highly repressed in cells growing rapidly on glucose, which is in accord with prior induction-repression studies. Moreover, the lack of a change in uptake flux during the bulk of batch growth is consistent with prior induction-repression studies. (3) The mutant exhibits a heightened sensitivity to CO2 as compared to wild-type counterparts. Growth rate is increased, and the production of formate, malate, glycerate, and pyruvate is reduced. This sensitivity illustrates that citrate synthase is more than an expendable component in an amphibolic pathway. Its presence in wild-type cells "immunizes" against the effect of CO2 fluctuations. (4) The effects of CO2 can be tentatively explained by assuming that the PEP carboxylase-catalyzed reaction is stimulated.
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PMID:Flux adaptations of citrate synthase-deficient Escherichia coli. 783 22

We hypothesized that augmented responses of glucoregulatory hormones in iron deficiency would enhance liver and muscle glycogenolysis, leading to increased gluconeogenic precursor (lactate) supply and upregulation of hepatic gluconeogenesis. Female weanling rats were randomly placed on either a mildly iron-deficient (-Fe; 15 mg Fe/kg diet) or an iron-sufficient (+Fe; 50 mg Fe/kg diet) diet for 4 wk and studied at rest and during exhaustive treadmill running. Hemoglobin was 9.0 +/- 0.2 and 13.1 +/- 0.3 g/dl in -Fe and +Fe, respectively, after 3.5 wk of dietary iron deficiency. Arterial plasma epinephrine (Epi), norepinephrine (NE), adrenocorticotropic hormone (ACTH), corticosterone, insulin, and glucagon levels were similar at rest in both groups, as were liver, gastrocnemius, and superficial and deep vastus medialis glycogen levels. Liver and kidney phosphoenolpyruvate carboxykinase (PEPCK) activities were similar in both groups. Maximum O2 consumption was decreased (22%) in -Fe. Respiratory exchange ratio (CO2 production/O2 consumption) was unaffected at rest but increased at maximum O2 consumption in -Fe. Time to exhaustion during a standardized running test (13.4 m/min, 0% grade) was decreased 45% in -Fe (63 +/- 5 vs. 116 +/- 10 min). During exercise, euglycemia was maintained in both groups, but blood lactate was elevated in -Fe. The mean net glycogen utilization during exercise was increased in liver (43%), soleus (33%), and superficial vastus medialis (106%) and decreased in the gastrocnemius (36%) in -Fe. Liver and kidney PEPCK activities were increased similarly at exhaustion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmented glucoregulatory hormone concentrations during exhausting exercise in mildly iron-deficient rats. 823 58

Incubation of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase with trypsin under native conditions cases a time-dependent loss of activity and the production of protein fragments. Cleavage sites determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and sequence analyses identified protease-sensitive peptide bonds between amino acid residues at positions 9-10 and 76-77. Additional fragmentation sites were also detected in a region approximately 70-80 amino acids before the carboxyl end of the protein. These results suggest that the enzyme is formed by a central compact domain comprising more than two thirds of the whole protein structure. From proteolysis experiments carried out in the presence of substrates, it could be inferred that CO2 binding specifically protects position 76-77 from trypsin action. Intrinsic fluorescence measurements demonstrated that CO2 binding induces a protein conformational change, and a dissociation constant for the enzyme CO2 complex of 8.2 +/- 0.6 mM was determined.
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PMID:Limited proteolysis of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase. 825 Oct 61


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