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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 distribution of alanine aminotransferase isozymes in several tissues from several species has been studied. In glycolytic tissues, such as skeletal and cardiac muscle, cytosolic alanine aminotransferase was the predominant form. In gluconeogenic tissues, such as liver and kidney, the concentration of the cytosolic alanine aminotransferase was much more variable; its presence, however, may be correlated with the presence of phosphoenolpyruvate carboxykinase in the same compartment. The particulate enzyme was found associated only with the matrix of the mitochondria. It was present only in those gluconeogenic tissues that can utilize alanine for glucose production, e.g. rat liver and pig liver and kidney; it was absent from rat kidney which cannot convert alanine to glucose. These observations, together with the kinetic parameters of the two isozymes, suggest that in vivo, mitochondrial alanine aminotransferase is involved in the conversion of alanine to pyruvate, while the cytosolic isoenzyme is mainly involved in the formation of alanine from pyruvate.
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PMID:Metabolic implications of the distribution of the alanine aminotransferase isoenzymes. 117 55

3-Mercaptopicolinic acid inhibited gluconeogenesis from lactate and alanine, but not dihydroxyacetone, in the perfused rat liver. Hepatic metabolite concentrations suggested that gluconeogenesis was inhibited at phosphoenolpyruvate carboxykinase. The compound is very effective at low concentrations, and seems an ideal agent for use in studying metabolic regulation involving gluconeogenesis and anaplerotic mechanisms.
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PMID:Effect of 3-mercaptopicolinic acid on gluconeogenesis and gluconeogenic metabolite concentrations in the isolated perfused rat liver. 120 Oct 6

The 3-day-old rat has a high basal level of phosphoenolpyruvate carboxykinase (PEPCK), the activity of which is not increased upon starvation. The lower basal activity of the enzyme in 19-day-old rat liver can, however, be stimulated by starvation. Serum glucose levels increased from 3 days to 19 days of age, with a decrease to adult levels. Liver glycogen concentration increased from 3 days to 19 days of age, with no additional increase observed at 3 months. There was a decrease with age in the specific activity of liver glycogen (from [14C]alanine and [14C]leucine). In fed rats given [14C]alanine, 14CO2 expiration tended to decrease with age. The 14CO2 production from [14C]leucine was less than that from alanine, and also decreased with age. Three-day-old rats showed no change in serum glucose when starved for 4 hr. On the other hand, 19-day-old rats responded with a decrease in serum glucose; although the adult animal's basal level of serum glucose was less than that of the 19-day-old rats, starvation for 15 hr also caused a significant decrease. There was no statistically significant difference in liver glycogen concentration between the fed and starved 3-day-old animals. Liver glycogen concentration in the 19-day-old adult rats was affected, however, by starvation. The 3-day-or glycogen during starvation. Starvation resulted in a tremendous increase in the specific activity of hepatic glycogen in the 19-day-old and adult rats. Starvation decreased the percentage of labeled amino acid expired as 14CO2. The proportion expired also decreased with age. Urinary nitrogen concentration increased significantly between 3 and 19 days of age. Starvation produced differential effects in the animals, with no change being observed in either the 3-day or adult rats; a decrease was observed in the 19-day-old animals. Urinary nitrogen concentration was measured in adult carbohydrate-deprived rats and was significantly higher than control values. These rats had a high gluconeogenic rate, reflected in the increased urinary nitrogen concentration. The young rat is at the mercy of a continuous supply of substrate in that it has a limited capacity for directing substrat
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PMID:Utilization of dietary amino acids for energy production in neonatal rat liver. 125 Jun 45

Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 1415C-alanine was reduced. In these 2 patients only 1.3-5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C-glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from C-alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step.
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PMID:Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia. 127 63

The activities of glucose-6-phosphatase (G6P), fructose diphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), aspartate and alanine transferases were measured in liver and kidney of fetal foals between 100-318 days of gestation (term approximately 335 days) and during the immediate postnatal period (0-48 h after birth). All 5 enzymes could be detected in the fetal liver and kidney at the youngest gestational age studied. Mean fetal activities were lower than those observed in their mothers and showed no change with gestational age for the majority of enzymes studied. However, renal PEPCK and renal and hepatic G6P did increase towards term. At birth, hepatic and renal activities of these two enzymes were higher than those found in late gestation or in the adult animals. There was no apparent change in the activities of any of the other enzymes at birth. In late gestation (80-90% gestation), the activities of G6P and PEPCK in the foal were low compared to those in other species at the same stage of gestation. Similarly, the perinatal increase in enzyme activity occurred closer to term in the foal than in most other species. These observations indicate that maturation of glucogenic capacity occurs relatively late in the fetal foal and suggests that this process may be dependent on the prepartum rise in fetal cortisol as occurs in other species.
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PMID:The development of gluconeogenic enzymes in the liver and kidney of fetal and newborn foals. 130 17

Incubation of isolated hepatocytes from fasted rats with 20 mM LiCl for 1 h decreased glucose production from lactate, pyruvate, and alanine. In addition, phosphoenolpyruvate carboxykinase (PEPCK) gene expression in FTO-2B rat hepatoma cells was inhibited by treatment with LiCl. Lithium was also able to counteract the increased PEPCK mRNA levels caused by both Bt2cAMP and dexamethasone, in a concentration-dependent manner. A chimeric gene containing the PEPCK promoter (-550 to +73) linked to the amino-3-glycosyl phosphotransferase (neo) structural gene was transduced into FTO-2B cells using a Moloney murine leukemia virus-based retrovirus. In these infected cells, 20 mM LiCl decreased both the concentration of neo mRNA transcribed from the PEPCK-neo chimeric gene and mRNA from the endogenous PEPCK gene. Lithium also inhibited the stimulatory effect of Bt2cAMP and dexamethasone on both genes. The stability of neo mRNA was not altered by lithium, since in cells infected with retrovirus containing only the neo gene transcribed via the retroviral 5'-LTR and treated with 20 mM LiCl, no change in neo mRNA levels was observed. The intraperitoneal administration of LiCl to rats caused a decrease in hepatic PEPCK mRNA, indicating that lithium could also modify gene expression in vivo. The effects of lithium were not due to an increase in the concentration of insulin in the blood but were correlated with an increase in hepatic glycogen and fructose 2,6-bisphosphate levels. These results indicate that lithium ions, at concentrations normally used therapeutically for depression in humans, can inhibit glucose synthesis in the liver by a mechanism which can selectively modify the expression of hepatic phosphoenolpyruvate carboxykinase.
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PMID:Lithium inhibits hepatic gluconeogenesis and phosphoenolpyruvate carboxykinase gene expression. 137 Nov 8

The consumption of glucose by trypanosomatid protozoa such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Crithidia spp. is characterized by the excretion of reduced products such as succinate, pyruvate, ethanol, L-alanine, or lactate (depending on the species) not only in anaerobiosis, but also under aerobic conditions. The "aerobic fermentation" of glucose is accompanied by a complete lack, or even a reversal, of the Pasteur effect. This peculiar catabolism is mediated by a so-far unique compartmentation of the glycolytic enzymes, most of which are placed in an organelle called the glycosome; by an almost complete lack of inhibitory controls at the level of hexokinase and phosphofructokinase; and by a central role of CO2 fixation through the reaction catalyzed by phosphoenolpyruvate carboxykinase. The production of fermentative products seems to be due to a relative inefficiency of the respiratory chain, which lacks NADH dehydrogenase and the first phosphorylation site and preferentially uses succinate as substrate.
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PMID:Aerobic fermentation of glucose by trypanosomatids. 139 37

Gluconeogenesis was studied in hepatocytes isolated from phenobarbital-pretreated rats fasted for 24 h. In closed vial incubations, glucose production from lactate (20 mmol/l) and pyruvate (2 mmol/l), alanine (20 mmol/l) or glutamine (20 mmol/l) was suppressed by about 30-45%, although glycerol metabolism was not affected. In hepatocytes perifused with lactate and pyruvate (ratio 10:1), glucose production was inhibited by 50%, even at low gluconeogenic flux. From the determination of gluconeogenic intermediates at several steady states of gluconeogenic flux, we have found a single relationship between phosphoenolpyruvate and the rate of glucose production (Jglucose), and two different curves between cytosolic oxaloacetate and Jglucose in controls and in phenobarbital-pretreated hepatocytes. By using 3-mercaptopicolinate to determine the flux control coefficient of phosphoenolpyruvate carboxykinase we found that phenobarbital pretreatment led to an increase in this coefficient from 0.3 (controls) to 0.8 (phenobarbital group). These observations were confirmed by the finding that the activity of phosphoenolpyruvate carboxykinase was decreased by 50% after phenobarbital treatment. Hence we conclude that the inhibitory effect of phenobarbital on gluconeogenesis is due, at least partly, to a decrease in the flux through phosphoenolpyruvate carboxykinase.
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PMID:Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital. 176 30

This study investigated the hypothesis that dehydroepiandrosterone (DHEA) functions as an antiobesity agent by promoting energy wastage via hepatic substrate cycling in prediabetic male BHE/cdb rats. Weanling BHE/cdb rats fed a 65% glucose diet were injected intraperitoneally daily with either DHEA (0.35 mol/kg body wt) or vehicle (1 mL/kg body wt) for 7 wk. The DHEA treatment significantly (P less than 0.05) reduced body weight gain. The DHEA-treated rats had epididymal and retroperitoneal fat pads that were 40% and 66% lighter, respectively, than those of control rats. The residual carcasses (i.e., minus fat pads, liver and ingesta) of DHEA-treated rats contained a significantly lower percentage of fat than those of control rats. The DHEA treatment significantly reduced fasting serum glucose and triglycerides without affecting total or HDL cholesterol. Isolated hepatocytes from DHEA-treated rats converted 2.5 times as much [U-14C]glucose to 14CO2 and one-half as much alanine to glucose as did hepatocytes from control rats. The DHEA treatment increased the specific activities of malic enzyme and lactate dehydrogenase 4.0- and 1.8-fold, respectively. Hepatocytes from DHEA-treated rats tended (P less than 0.08) to have lower phosphoenolpyruvate carboxykinase activities than hepatocytes from control rats. These data suggest that DHEA treatment exerts some of its antiobesity and antidiabetic effects in prediabetic, lipemic BHE/cdb rats by promoting hepatic glucose oxidation and reducing gluconeogenesis.
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PMID:Antiobesity effects of dehydroepiandrosterone are mediated by futile substrate cycling in hepatocytes of BHE/cdb rats. 183 18

Nitrate and alanine were found to stimulate partially purified maize leaf phosphoenolpyruvate carboxylase under specific assay conditions. Both metabolites stimulated the enzyme at low pH (7.0-7.5) and low substrate levels (1mM phosphoenolpyruvate). Nitrate was found to have a biphasic effect on the enzyme, stimulating at low concentrations (1mM-3mM), with a decrease in stimulation at higher levels. Nitrate caused inhibition of activity at pH 8.0 and although alanine caused some stimulation in activity at pH 8.0 this was not as marked as at the lower pH levels.
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PMID:Regulation of phosphoenolpyruvate carboxylase from maize leaves by nitrate and alanine. 185 33


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