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:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ratio of the combined activities of hexokinase (EC 2.7.1.1) and glucokinase (EC 2.7.1.2) to the activity of glucose-6-phosphatase (EC 3.1.3.9) changed in favour of the glycolytic enzymes during pregnancy and at peak lactation. 2. There were no important changes in the ratio of the activity of phosphofructokinase (EC 2.7.1.11) to that of fructose diphosphatase (EC 3.1.3.11). 3. The ratio of the activity of pyruvate kinase (EC 2.7.1.40) to the combined activities of phosphoenolpyruvate carboxylase (EE 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) changed in favour of the glycolytic enzyme during pregnancy and at peak lactation, but changed in favour of the gluconeogenic enzymes immediately after parturition. 4. These changes are considered in relation to the changes in food intake and hormonal status that occur during pregnancy and lactation.
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PMID:The effects of pregnancy and lactation on the activities in rat liver of some enzymes associated with glucose metabolism. 17 Sep 98

1. Oral administration of ethanol (3 ml) of 95% in 12 ml total volume over a two day period) significantly decrease plasma glucose and insulin levels and the activities of two key gluconeogenic enzymes, pyruvate carboxylase (pyruvate: CO2 ligase (ADP), EC 6.4.1.1) and fructose diphosphatase, (D-Fru-1,6-P2 1-phosphohydrolase, EC 3.1.3.11), and one glycolytic enzyme, fructose-1,6-P2 aldolase (Fru-1,6-P2 D-glyceraldehyde-3-P lyase, EC 4.1.2.13). In each instance, the administration of 2400 mug daily of oral folate in conjuction with the ethanol prevented these alterations in carbohydrate metabolism. 2. Intravenous injection of ethanol produced a rapid decrease (within 10--15 min) in the activities of hepatic phosphofructokinase, (ATP:D-fructose-6-phosphate 6-phosphotransferase, EC 2.7.1.11), pyruvate kinase, (ATP:pyruvate phosphotransferase, EC 2.7.1.40), fructose diphosphatase and fructose-1,6-P2 aldolase. 3. Intravenous ethanol significantly increased hepatic cyclic AMP concentration approximately 60% within 10 min, while oral ethanol did not alter hepatic cyclic AMP concentrations. 4. These data confirm the known antagonism ethanol and folate and suggest that oral folate might offer a protective effect against hypoglycemia in rats receiving ethanol.
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PMID:Acute effects of oral and intravenous ethanol on rat hepatic enzyme activities. 17 81

Male Sprague-Dawley rats (240-245 g) were dosed ip with 5, 15, 25, or 125 micrograms/kg -,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in corn oil. Ad libitum-fed and pair-fed controls received vehicle (4 ml/kg) alone. Two or 8 days after dosing five rats of each group were sacrificed, their livers removed and assayed for the activities of three gluconeogenic enzymes [phosphoenol-pyruvate carboxykinase (PEPCK; EC 4.1.1.32), pyruvate carboxylase (PC; EC 6.4.1.1), and glucose-6-phosphatase (G-6-Pase, EC 3.13.9)], and one glycolytic enzyme [pyruvate kinase (PK; EC 2.7.1.40)] by established procedures. The activity of PK was not affected by TCDD at either time point. The activity of G-6-Pase tended to be decreased in TCDD-treated animals, as compared to pair-fed controls, but the decrease was variable without an apparent dose-response. The activity of PEPCK was significantly decreased 2 days after dosing, but a clear dose-response was apparent only at the 8-day time point. Maximum loss of activity at the highest dose was 56% below pair-fed control levels. PC activity was slightly decreased 2 days after TCDD treatment and displayed statistically significant, dose-dependent reduction by 8 days after dosing with a 49% loss of enzyme activity after the highest dose. It is concluded that inhibition of gluconeogenesis by TCDD previously demonstrated in vivo is probably due to decreased activities of PEPCK and PC. The data also support the prevailing view that PEPCK and PC are rate-determining enzymes in gluconeogenesis.
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PMID:Key enzymes of gluconeogenesis are dose-dependently reduced in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats. 205 51

We have used control analysis to quantify the distribution of control in the gluconeogenic pathway in liver cells from starved rats. Lactate and pyruvate were used as gluconeogenic substrates. The flux control coefficients of the various enzymes in the gluconeogenic pathway were calculated from the elasticity coefficients of the enzymes towards their substrates and products and the fluxes through the different branches in the pathway. The elasticity coefficients were either calculated from gamma/Keq. ratios (where gamma is the mass-action ratio and Keq. is the equilibrium constant) and enzyme-kinetic data or measured experimentally. It is concluded that the gluconeogenic enzyme pyruvate carboxylase and the glycolytic enzyme pyruvate kinase play a central role in control of gluconeogenesis. If pyruvate kinase is inactive, gluconeogenic flux from lactate is largely controlled by pyruvate carboxylase. The low elasticity coefficient of pyruvate carboxylase towards its product oxaloacetate minimizes control by steps in the gluconeogenic pathway located after pyruvate carboxylase. This situation occurs when maximal gluconeogenic flux is required, i.e. in the presence of glucagon. In the absence of the hormone, when pyruvate kinase is active, control of gluconeogenesis is distributed among many steps, including pyruvate carboxylase, pyruvate kinase, fructose-1,6-bisphosphatase and also steps outside the classic gluconeogenic pathway such as the adenine-nucleotide translocator.
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PMID:Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon. 380 Aug 95

The gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) and the glycolytic enzyme pyruvate kinase (PK), regulating pyruvate metabolism, were determined in the livers of 71 fetuses, which were developed of 25 dams on the 80th, 100th, 106th, and 112th day of gestation (length: 115 days) by Caesarean section. For comparative purposes the same enzymes were estimated in 12 naturally born piglets immediately after delivery. During the period under examination (the last third of gestation) the total activity of PEPCK has its highest values at the 80th day, the PC and PK activity at the 100th day of gestation. The activities of all 3 enzymes decrease during the last 2 weeks of gestation until birth. The cytosolic part of PEPCK amounts to 10-15 per cent of total activity and develops in a parallel manner. In newborn piglets a further decline of the PC and total PEPCK activity can be observed, but the cytosolic PEPCK activity remains constant, and therefore its relative proportion increases to 25% of the total activity. The PK activity rises distinctly (1.5 times). The role of these enzymes in the carbohydrate metabolism of the fetus, especially in gluconeogenesis, is discussed in detail.
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PMID:[Perinatal development of the pyruvate metabolism-regulating enzyme in the pig liver]. 714 69

Campylobacter jejuni is unable to utilize glucose as a carbon source due to the absence of the key glycolytic enzyme 6-phosphofructokinase. The genome sequence of C. jejuni NCTC 11168 indicates that homologues of all the appropriate enzymes for gluconeogenesis from phosphoenolpyruvate (PEP) are present, in addition to the anaplerotic enzymes pyruvate carboxylase (PYC), phosphoenolpyruvate carboxykinase (PCK) and malic enzyme (MEZ). Surprisingly, a pyruvate kinase (PYK) homologue is also present. To ascertain the role of these enzymes, insertion mutants in pycA, pycB, pyk and mez were generated. However, this could not be achieved for pckA, indicating that PCK is an essential enzyme in C. jejuni. The lack of PEP synthase and pyruvate orthophosphate dikinase activities confirmed a unique role for PCK in PEP synthesis. The pycA mutant was unable to grow in defined medium with pyruvate or lactate as the major carbon source, thus indicating an important role for PYC in anaplerosis. Sequence and biochemical data indicate that the PYC of C. jejuni is a member of the alpha4beta4, acetyl-CoA-independent class of PYCs, with a 65.8 kDa subunit containing the biotin moiety. Whereas growth of the mez mutant was comparable to that of the wild-type, the pyk mutant displayed a decreased growth rate in complex medium. Nevertheless, the mez and pyk mutants were able to grow with pyruvate, lactate or malate as carbon sources in defined medium. PYK was present in cell extracts at a much higher specific activity [>800 nmol x min(-1) x (mg protein)(-1)] than PYC or PCK [<65 nmol x min(-1) x (mg protein)(-1)], was activated by fructose 1,6-bisphosphate and displayed other regulatory properties strongly indicative of a catabolic role. It is concluded that PYK may function in the catabolism of unidentified substrates which are metabolized through PEP. In view of the high K(m) of MEZ for malate (approximately 9 mM) and the lack of a growth phenotype of the mez mutant, MEZ seems to have only a minor anaplerotic role in C. jejuni.
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PMID:Analysis of gluconeogenic and anaplerotic enzymes in Campylobacter jejuni: an essential role for phosphoenolpyruvate carboxykinase. 1188 2

We have proposed that hyperglycemia-induced dedifferentiation of beta-cells is a critical factor for the loss of insulin secretory function in diabetes. Here we examined the effects of the duration of hyperglycemia on gene expression in islets of partially pancreatectomized (Px) rats. Islets were isolated, and mRNA was extracted from rats 4 and 14 weeks after Px or sham Px surgery. Px rats developed different degrees of hyperglycemia; low hyperglycemia was assigned to Px rats with fed blood glucose levels less than 150 mg/dl, and high hyperglycemia was assigned above 150 mg/dl. beta-Cell hypertrophy was present at both 4 and 14 weeks. At the same time points, high hyperglycemia rats showed a global alteration in gene expression with decreased mRNA for insulin, IAPP, islet-associated transcription factors (pancreatic and duodenal homeobox-1, BETA2/NeuroD, Nkx6.1, and hepatocyte nuclear factor 1 alpha), beta-cell metabolic enzymes (glucose transporter 2, glucokinase, mitochondrial glycerol phosphate dehydrogenase, and pyruvate carboxylase), and ion channels/pumps (Kir6.2, VDCC beta, and sarcoplasmic reticulum Ca(2+)-ATPase 3). Conversely, genes normally suppressed in beta-cells, such as lactate dehydrogenase-A, hexokinase I, glucose-6-phosphatase, stress genes (heme oxygenase-1, A20, and Fas), and the transcription factor c-Myc, were markedly increased. In contrast, gene expression in low hyperglycemia rats was only minimally changed at 4 weeks but significantly changed at 14 weeks, indicating that even low levels of hyperglycemia induce beta-cell dedifferentiation over time. In addition, whereas 2 weeks of correction of hyperglycemia completely reverses the changes in gene expression of Px rats at 4 weeks, the changes at 14 weeks were only partially reversed, indicating that the phenotype becomes resistant to reversal in the long term. In conclusion, chronic hyperglycemia induces a progressive loss of beta-cell phenotype with decreased expression of beta-cell-associated genes and increased expression of normally suppressed genes, these changes being present with even minimal levels of hyperglycemia. Thus, both the severity and duration of hyperglycemia appear to contribute to the deterioration of the beta-cell phenotype found in diabetes.
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PMID:Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetes. 1243 14

Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative response of the organism to stimulate gluconeogenesis. They showed for the first time that HCB causes impairment of the gluconeogenic pathway. Therefore, the reduced levels of glucose would thus be the consequence of decreased gluconeogenesis, enhanced glucose storage, and unaffected glycolysis. The impairment of gluconeogenesis (especially for PEPCK) and the related variation in glucose levels caused by HCB treatment could be a consequence of the oxidative stress produced by the fungicide. Tryptophan adds its effect to this decrease in the higher phases of HCB intoxication, where its levels overcome the control values possibly owing to the drastic decline of URO-D. This derangement of carbohydrates leads porphyric hepatocytes to have lower levels of free glucose. These results contribute to our understanding of the protective and modulatory effect that diets rich in carbohydrates have in hepatic porphyria disease.
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PMID:Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach. 1289 29

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