scholarly journals Physiological concentrations of 2-oxoglutarate regulate the activity of phosphoenolpyruvate carboxykinase in liver

1992 ◽  
Vol 285 (3) ◽  
pp. 767-771 ◽  
Author(s):  
M A Titheradge ◽  
R A Picking ◽  
R C Haynes
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Hepatocytes ◽  
Fasted State ◽  
Stimulation Of

2-Oxoglutarate was found to inhibit purified rat liver phosphoenolpyruvate carboxykinase when the assay was performed in the direction of either phosphoenolpyruvate or oxaloacetate synthesis. The inhibition was competitive with respect to oxaloacetate or phosphoenolpyruvate, the Ki values being 0.32 +/- 0.04 mM 0.63 +/- 0.19 mM respectively. 2-Oxoglutarate inhibited non-competitively when tested against GTP or Mn2+. The reported cytosolic concentrations of 2-oxoglutarate in rat hepatocytes are such that the enzyme is likely to be significantly inhibited under basal conditions. The cytosolic concentration of 2-oxoglutarate is known to fall precipitously under the influence of glucagon and other hormones that stimulate gluconeogenesis, and it is suggested that the hormone-induced decrease in 2-oxoglutarate content would alleviate the inhibition of phosphoenolpyruvate carboxykinase and stimulate flux from oxaloacetate to phosphoenolpyruvate. The implications of this finding to the rationalization of the role of pyruvate kinase in the stimulation of gluconeogenesis in the fasted state are discussed.

scholarly journals The rôle of mitochondrial pyruvate transport in the stimulation by glucagon and phenylephrine of gluconeogenesis from l-lactate in isolated rat hepatocytes

1981 ◽  
Vol 198 (3) ◽  
pp. 551-560 ◽  
Author(s):  
A P Thomas ◽  
A P Halestrap
Keyword(s):  
Pyruvate Kinase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Pyruvate Kinase Activity ◽  
Isolated Rat Hepatocytes ◽  
Isolated Liver Cells ◽  
Additional Role ◽  
Isolated Liver

The sensitivity of glucose production from L-lactate by isolated liver cells from starved rats to inhibition by alpha-cyano-4-hydroxycinnamate was studied. A small percentage of the maximal rate of gluconeogenesis was insensitive to inhibition by alpha-cyano-4-hydroxycinnamate, and evidence is presented to show that this is due to pyruvate entry into the mitochondria as alanine. After subtraction of this rate, Dixon plots of the reciprocal of the rate of gluconeogenesis against inhibitor concentration were linear both in the absence and presence of glucagon, phenylephrine or valinomycin, each of which stimulated gluconeogenesis by 30-50%. Pyruvate kinase activity was decreased by glucagon, but not by phenylephrine or valinomycin. Inhibition of gluconeogenesis by quinolinate (inhibitor of phosphoenolpyruvate carboxykinase) or monochloroacetate (probably inhibiting pyruvate carboxylation) caused a significant deviation from linearity of the Dixon plot obtained with alpha-cyano-4-hydroxycinnamate. Amytal, however, inhibited gluconeogenesis without affecting the linearity of this plot. These data, coupled with a computer simulation study, suggest that pyruvate transport may control gluconeogenesis from L-lactate and that hormones may stimulate this process through an effect on the respiratory chain. An additional role for pyruvate kinase and pyruvate carboxylase is quite compatible with the data presented.

Stimulation of Active Na+and K+Transport by Thyroid Hormone in a Rat Liver Cell Line: Role of Enhanced Na+Entry*

Endocrinology ◽  
1986 ◽  
Vol 119 (6) ◽  
pp. 2527-2536 ◽  
Author(s):  
FARAMARZ ISMAIL-BEIGI ◽  
RICHARD S. HABER ◽  
JOHN N. LOEB
Keyword(s):  
Thyroid Hormone ◽  
Cell Line ◽  
Rat Liver ◽  
Liver Cell ◽  
Liver Cell Line ◽  
K Transport ◽  
Stimulation Of

scholarly journals Role of cytoplasmic thioltransferase in cellular regulation by thiol-disulphide interchange

1980 ◽  
Vol 190 (1) ◽  
pp. 125-130 ◽  
Author(s):  
B Mannervik ◽  
K Axelsson
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Protein Fraction ◽  
Cellular Regulation ◽  
General Role ◽  
Regulatory Processes ◽  
Glutathione Status ◽  
Glutathione Disulphide

Cytoplasmic thioltransferase purified from rat liver [Axelsson, Eriksson & Mannervik (1978) Biochemistry 17, 2978–2984] catalyses the formation and decomposition of mixed disulphides of proteins and glutathione. The enzyme was found to catalyse the reversible thiol-disulphide interchange between glutathione disulphide and a crude thiol-containing protein fraction from rat liver. This finding indicates a role of the thioltransferase in the regulation of the ‘glutathione status’ of the cell. Specifically, it was found that thioltransferase catalyses the reactivation of pyruvate kinase from rat liver that had previously been inactivated by glutathione disulphide. It is suggested that thioltransferase may have a general role in regulatory processes involving thiol-disulphide interchange.

Regulation of phosphoenolpyruvate carboxykinase and pyruvate kinase in Saccharomyces cerevisiae grown in the presence of glycolytic and gluconeogenic carbon sources and the role of mitochondrial function on gluconeogenesis

1986 ◽  
Vol 32 (12) ◽  
pp. 969-972 ◽  
Author(s):  
Albert J. Wilson ◽  
J. K. Bhattacharjee
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Pyruvate Kinase ◽  
Growth Medium ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Carbon Sources ◽  
Absolute Requirement ◽  
Fructose 1,6 Bisphosphatase ◽  
Futile Cycling ◽  
Respiratory Deficient

Phosphoenolpyruvate carboxykinase (PEPCKase) and pyruvate kinase (PKase) were measured in Saccharomyces cerevisiae grown in the presence of glycolytic and gluconeogenic carbon sources. The PEPCKase activity was highest in ethanol-grown cells. However, high PEPCKase activity was also observed in cells grown in 1% glucose, especially as compared with the activity of sucrose-, maltose-, or galactose-grown cells. Activity was first detected after 12 h when glucose was exhausted from the growth medium. The PKase activity was very high in glucose-grown cells; considerable activity was also present in ethanol- and pyruvate-grown cells. The absolute requirement of respiration for gluconeogenesis was demonstrated by the absence or significantly low levels of PEPCKase and fructose-1,6-bisphosphatase activities observed in respiratory deficient mutants, as well as in wild-type S. cerevisiae cells grown in the presence of glucose and antimycin A or chloramphenicol. Obligate glycolytic and gluconeogenic enzymes were present sumultaneously only in stationary phase cells, but not in exponential phase cells; hence futile cycling could not occur in log phase cells regardless of the presence of carbon source in the growth medium.

scholarly journals Induction of mRNA for phosphoenolpyruvate carboxykinase (GTP) by dexamethasone in cultured rat hepatocytes requires on-going protein synthesis

1987 ◽  
Vol 246 (1) ◽  
pp. 237-240 ◽  
Author(s):  
V L Nebes ◽  
S M Morris
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Hepatocytes ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Maximum Induction ◽  
Cultured Rat Hepatocytes ◽  
Time Required ◽  
Necessary And Sufficient ◽  
Stimulation Of

Dexamethasone is necessary and sufficient to induce mRNA for phosphoenolpyruvate carboxykinase (GTP) (PEPCK) by 19-fold in rat hepatocytes cultured in serum-free medium. However, the time required for maximum induction is 16 h. The slow induction suggested that glucocorticoids regulate the expression of an intermediate gene product(s) which is required for glucocorticoid stimulation of PEPCK-gene expression. Consistent with this notion was the finding that cycloheximide completely blocked the response to dexamethasone. In contrast, cycloheximide did not block the response to a cyclic AMP analogue.

scholarly journals The Role of Collagen Structure in Mitogen Stimulation of ERK, Cyclin D1 Expression, and G1-S Progression in Rat Hepatocytes

2003 ◽  
Vol 278 (34) ◽  
pp. 31691-31700 ◽  
Author(s):  
John T. Fassett ◽  
Diane Tobolt ◽  
Christopher J. Nelsen ◽  
Jeffrey H. Albrecht ◽  
Linda K. Hansen
Keyword(s):  
Cyclin D1 ◽  
Rat Hepatocytes ◽  
Collagen Structure ◽  
Mitogen Stimulation ◽  
Stimulation Of

scholarly journals Activation and inactivation of phosphoenolpyruvate carboxykinase by ferrous ions

1980 ◽  
Vol 185 (2) ◽  
pp. 451-454 ◽  
Author(s):  
C H Reynolds
Keyword(s):  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Protein Fractions ◽  
Time Dependent ◽  
Ferrous Ions ◽  
Irreversible Loss ◽  
Liver Cytosol ◽  
Rat Liver Cytosol

Phosphoenolpyruvate carboxykinase from rat liver cytosol is activated by Fe2+ ions in either direction of catalysis. Preincubation of the purified enzyme with Fe2+ ions causes a time-dependent irreversible loss of activity; this is not seen with unpurified enzyme. Purified enzyme can be protected from inactivation by Fe2+ ions by partially purified protein fractions from liver (ferroactivator fractions). The possible role of ferroactivator and Fe2+ ions in regulating phosphoenolpyruvate carboxykinase is discussed.

scholarly journals myo-Inositol is an osmolyte in rat liver macrophages (Kupffer cells) but not in RAW 264.7 mouse macrophages

1997 ◽  
Vol 326 (1) ◽  
pp. 289-295 ◽  
Author(s):  
Ulrich WARSKULAT ◽  
Christian WEIK ◽  
Dieter HÄUSSINGER
Keyword(s):  
Rat Liver ◽  
Kupffer Cells ◽  
Mrna Level ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Mouse Macrophages ◽  
Taurine Uptake ◽  
Inositol Uptake ◽  
Stimulation Of

The role of myo-inositol as an osmolyte was studied in cultured rat liver macrophages (Kupffer cells). Hyperosmotic exposure of Kupffer cells stimulated myo-inositol uptake and led to an increase in the mRNA levels for the sodium/myo-inositol co-transporter (SMIT). Conversely, hypo-osmotic (205 m-osM) exposure diminished myo-inositol uptake when compared with normo-osmotic (305 m-osM) control incubations. The hyperosmolarity-induced SMIT mRNA increase was counteracted by added myo-inositol or betaine. In contrast with Kupffer cells, there was only a slight hyperosmotic stimulation of myo-inositol uptake in RAW 264.7 mouse macrophages, and the myo-inositol transporter (SMIT) mRNA was not detectable. Further, a slight stimulation of taurine uptake and an increase in taurine transporter (TAUT) mRNA level by hyperosmolarity was observed in RAW 264.7 cells, whereas hypo-osmolarity led to a decrease in taurine uptake and TAUT mRNA level. When Kupffer cells were preloaded with myo-inositol, hypo-osmotic exposure led to a rapid efflux of myo-inositol from the cells. Myo-inositol efflux was also stimulated by phagocytosis of latex particles; however, latex was without effect on the hyperosmolarity-induced increase of SMIT mRNA levels. The results suggest a role of myo-inositol as an osmolyte in rat Kupffer cells but not in RAW 264.7 mouse macrophages. The functional relevance of this osmolyte strategy might lie in the maintenance of cell volume homeostasis during phagocytosis in Kupffer cells; however, the interplay with the other osmolytes betaine and taurine remains to be established.

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