scholarly journals The development of gluconeogenesis in rat liver. Effects of glucagon and ether

1970 ◽  
Vol 120 (2) ◽  
pp. 385-392 ◽  
Author(s):  
Helen Philippidis ◽  
F. J. Ballard
Keyword(s):  
Rat Liver ◽  
Redox State ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fold Increase ◽  
Similar Increase ◽  
Ether Anaesthesia ◽  
Foetal Liver ◽  
Foetal Rat ◽  
Newborn Animals

1. Administration of glucagon to foetal rats produced a 10–15-fold increase in hepatic phosphoenolpyruvate carboxykinase activity together with a similar increase in the overall pathway of pyruvate conversion into glycogen in liver slices. 2. Glucagon was without effect on gluconeogenesis in vivo, which remained at approx. 0.1% of the incorporation as measured in newborn animals. 3. The apparent discrepancy between these results was due to the ether anaesthesia that was required for experimentation in vivo. Under conditions when minimal ether was used, the rates of labelling of glycogen from [3-14C]pyruvate in vivo were increased 10–20-fold and there was an additional stimulus by glucagon. 4. Ether anaesthesia produced a more reduced redox state of the foetal liver cytosol and lowered the ATP/ADP concentration ratio. 5. It is proposed that these effects are significant in the limitation of gluconeogenesis in the foetal rat liver, so that only with high phosphoenolpyruvate carboxykinase activity, high ATP concentration and a relatively oxidized cytosol redox state will a functional gluconeogenic pathway be present.

scholarly journals The development of gluconeogenesis in rat liver. Experiments in vivo

1969 ◽  
Vol 113 (4) ◽  
pp. 651-657 ◽  
Author(s):  
Helen Philippidis ◽  
F. J. Ballard
Keyword(s):  
Rat Liver ◽  
Redox State ◽  
Fold Increase ◽  
Newborn Rats ◽  
Foetal Liver ◽  
Tracer Experiments ◽  
Newborn Animals

1. The injection of substrate amounts of lactate into newborn rats produced an increase in the concentration of phosphoenolpyruvate in liver. Similar experiments with foetal rats showed no increase in phosphoenolpyruvate concentration although pyruvate formation was observed. 2. The administration of pyruvate to foetal rats was also without effect on the hepatic phosphoenolpyruvate concentration, although a 20-fold increase in this was observed when pyruvate was injected into newborn animals. 3. Analogous experiments with aspartate produced qualitatively similar differences between foetal and newborn rats. 4. When [14C]-lactate, -pyruvate or -aspartate was injected into foetal or newborn rats incorporation of radioactivity into liver glucose was observed only in the newborn animals. 5. Lactate/pyruvate ratios of 213 in foetal liver and 13·5 in the livers of newborn rats indicated a relatively reduced environment in the cytosol of foetal liver. This difference in redox state was illustrated experimentally by a greater conversion of pyruvate into lactate and an increased formation of malate in foetal liver. 6. Although both the substrate-loading and tracer experiments indicated a block in gluconeogenesis in foetal liver at the stage of conversion of oxaloacetate into phosphoenolpyruvate, gluconeogenesis was also hindered by a highly reduced environment.

scholarly journals The role of prolactin and progesterone in the regulation of lipogenesis in maternal and foetal rat liver in vivo and in isolated hepatocytes during the last day of gestation

1986 ◽  
Vol 239 (1) ◽  
pp. 135-139 ◽  
Author(s):  
M Lorenzo ◽  
C Roncero ◽  
M Benito
Keyword(s):  
Rat Liver ◽  
Lipid Synthesis ◽  
Isolated Hepatocytes ◽  
Hepatic Lipogenesis ◽  
Treatment Conditions ◽  
Foetal Liver ◽  
Foetal Rat

The administration of progesterone on day 21 of gestation increases the rates of lipogenesis in the liver in vivo and in hepatocytes isolated from rats on day 22 of pregnancy. Bromocriptine administration increases the rates of hepatic lipogenesis in vivo, but has no effect on lipid synthesis in hepatocytes under the same treatment conditions. Concurrently, the administration of progesterone or bromocriptine on day 21 to the mother increases the rates of lipogenesis in the foetal liver in vivo on day 22. The rates of lipid synthesis in foetal isolated hepatocytes are increased by progesterone administration, but remain unchanged by bromocriptine.

scholarly journals Inhibitory effects of histidine and their reversal. The roles of pyruvate carboxylase and N10-formyltetrahydrofolate dehydrogenase

1979 ◽  
Vol 177 (3) ◽  
pp. 833-846 ◽  
Author(s):  
M C Scrutton ◽  
I Beis
Keyword(s):  
Rat Liver ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Specific Activity ◽  
Competitive Inhibitor ◽  
Product Inhibition ◽  
Detectable Effect ◽  
Formyltetrahydrofolate Dehydrogenase ◽  
Hydrolysis Of

1. N10-Formyltetrahydrofolate dehydrogenase was purified to homogeneity from rat liver with a specific activity of 0.7–0.8 unit/mg at 25 degrees C. The enzyme is a tetramer (Mw = 413,000) composed of four similar, if not identical, substrate addition and give the Km values as 4.5 micron [(-)-N10-formyltetrahydrofolate] and 0.92 micron (NADP+) at pH 7.0. Tetrahydrofolate acts as a potent product inhibitor [Ki = 7 micron for the (-)-isomer] which is competitive with respect to N10-formyltetrahydrofolate and non-competitive with respect to NADP+. 3. Product inhibition by NADPH could not be demonstrated. This coenzyme activates N10-formyltetrahydrofolate dehydrogenase when added at concentrations, and in a ratio with NADP+, consistent with those present in rat liver in vivo. No effect of methionine, ethionine or their S-adenosyl derivatives could be demonstrated on the activity of the enzyme. 4. Hydrolysis of N10-formyltetrahydrofolate is catalysed by rat liver N10-formyltetrahydrofolate dehydrogenase at 21% of the rate of CO2 formation based on comparison of apparent Vmax. values. The Km for (-)-N10-folate is a non-competitive inhibitor of this reaction with respect to N10-formyltetrahydrofolate, with a mean Ki of 21.5 micron for the (-)-isomer. NAD+ increases the maximal rate of N10-formyltetrahydrofolate hydrolysis without affecting the Km for this substrate and decreases inhibition by tetrahydrofolate. The activator constant for NAD+ is obtained as 0.35 mM. 5. Formiminoglutamate, a product of liver histidine metabolism which accumulates in conditions of excess histidine load, is a potent inhibitor of rat liver pyruvate carboxylase, with 50% inhibition being observed at a concentration of 2.8 mM, but has no detectable effect on the activity of rat liver cytosol phosphoenolpyruvate carboxykinase measured in the direction of oxaloacetate synthesis. We propose that the observed inhibition of pyruvate carboxylase by formiminoglutamate may account in part for the toxic effect of excess histidine.

scholarly journals A comparison of the effects of diabetes induced with either alloxan or streptozotocin and of starvation on the activities in rat liver of the key enzymes of gluconeogenesis

1970 ◽  
Vol 120 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Janet M. Wimhurst ◽  
K. L. Manchester
Keyword(s):  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Single Gene ◽  
Significant Rise ◽  
Liver Sample ◽  
Key Enzymes ◽  
Activity Unit ◽  
Wet Weight ◽  
Dna 2

1. Measurements of the activities in rat liver of the four key enzymes involved in gluconeogenesis, i.e. pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxykinase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), have been carried out, all four enzymes being measured in the same liver sample. Changes in activities resulting from starvation and diabetes have been studied. Changes in concentration (activity/unit wet weight of tissue) were compared with changes in the hepatic cellular content (activity/unit of DNA). 2. Each enzyme was found to increase in concentration during starvation for up to 3 days, but only glucose 6-phosphatase and phosphoenolpyruvate carboxykinase showed a significant rise in content. Fructose 1,6-diphosphatase appeared to decrease in content somewhat during the early stages of starvation. 3. There was a marked increase in the concentration of all four enzymes in non-starved rats made diabetic with alloxan or streptozotocin, for the most part similar responses being found for the two diabetogenic agents. On starvation, however, the enzyme contents in the diabetic animals tended to fall, often with streptozotocin-treated animals to values no greater than for the normal overnight-starved rat. Deprivation of food during the period after induction of diabetes with streptozotocin lessened the rise in enzyme activity. 4. The results are compared with other published values and factors such as substrate and activator concentrations likely to influence activity in vivo are considered. 5. Lack of correlation of change in fructose 1,6-diphosphatase with the other enzymes questions whether it should be included in any postulation of control of gluconeogenic enzymes by a single gene unit.

scholarly journals Differential effects of tryptophan on glucose synthesis in rats and guinea pigs

1978 ◽  
Vol 176 (3) ◽  
pp. 817-825 ◽  
Author(s):  
S A Smith ◽  
K R F Elliott ◽  
C I Pogson
Keyword(s):  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Liver Cells ◽  
Isolated Rat Hepatocytes ◽  
Rat Liver Cells ◽  
Glucose Output ◽  
Isolated Rat

1. Tryptophan inhibition of gluconeogenesis in isolated rat liver cells is characterized by a 20 min lag period before linear rates of glucose output are attained. 2. Half-maximal inhibition of gluconeogenesis in isolated rat hepatocytes is produced by approx. 0.1 mM-tryptophan. 3. Tryptophan inhibits gluconeogenesis from all substrates giving rise to oxaloacetate, but stimulates glycerol-fuelled glucose production. 4. Gluconeogenesis in guinea-pig hepatocytes is insensitive to tryptophan. 5. Changes in metabolite concentrations in rat liver cells are consistent with a locus of inhibition at the step catalysed by phosphoenolpyruvate carboxykinase. 6. Inhibition of gluconeogenesis persists in cells from rats pretreated with tryptophan in vivo. 7. Tryptophan has no effect on urea production from alanine, but decreases [1-14C]palmitate oxidation to 14CO2 and is associated with an increased [hydroxybutyrate]/[acetoacetate] ratio. 8. These results are discussed with reference to the control of gluconeogenesis in various species.

scholarly journals Development of adenylate kinase isoenzymes in rat liver

1971 ◽  
Vol 122 (4) ◽  
pp. 553-555 ◽  
Author(s):  
R. Filler ◽  
W. E. Criss
Keyword(s):  
Rat Liver ◽  
Liver Cell ◽  
Adenylate Kinase ◽  
Energy Flow ◽  
Kinase Activity ◽  
Adult Liver ◽  
Foetal Liver ◽  
Foetal Rat ◽  
Wet Weight ◽  
Developing Rat

Total adenylate kinase activity was determined in developing rat liver. The activity was 18 units/g wet weight of tissue in foetal liver; this increased to 41 units/g immediately after birth and continued increasing until adult activities of 150 units/g were reached after two weeks. The adenylate kinase activity was separated into four isoenzymes. Only isoenzymes II and III were observed in foetal rat liver. Isoenzyme II activity was 2 units/g in the foetal liver and increased to 25 units/g in adult liver. Adenylate kinase III activity was 20 units/g in the foetal liver and increased to 118 units/g in adult liver. The possible role that adenylate kinase might have in regulating the energy flow in the developing liver cell is discussed.

scholarly journals A physiological role of Mn2+ in the regulation of cytosolic phosphoenolpyruvate carboxykinase from rat liver is unlikely

1993 ◽  
Vol 292 (2) ◽  
pp. 365-370 ◽  
Author(s):  
S Maggini ◽  
F B Stoecklin-Tschan ◽  
S Mörikofer-Zwez ◽  
P Walter
Keyword(s):  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Physiological Role ◽  
Chelating Agent ◽  
Molecular Forms ◽  
Experimental Conditions ◽  
Free System ◽  
Inactivation Curve ◽  
Gluconeogenic Enzyme

A cytosolic cell-free system prepared from rat liver was used to study the effect of bivalent cations on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Steady-state concentrations of oxaloacetate in the range 5-50 microM were generated from increasing concentrations of malate+fumarate (10:1); 2 mM ITP and 3 mM Mg2+ were added as cofactors. Micromolar concentrations of Mn2+, Fe2+ and, to a lesser extent, of Zn2+ and Co2+ were shown to stimulate PEPCK activity. Vmax. (mumol/min per g of liver) increased from 0.67 to 1.68 on addition of 5 microM Fe2+ and to 2.34 with 2 microM Mn2+, whereas no significant effect on the Km for oxaloacetate was observed. The apparent K(a) values (total) were 0.62 microM for Mn2+, 1.48 microM for Zn2+, 1.92 microM for Co2+ and 3.37 microM for Fe2+, being 2-8-fold lower than the corresponding published values. Variations of the free Mn2+ concentration were obtained (a) by increasing the Mn2+ concentration (i.e. activation curve) and (b) by simultaneous addition of Mn2+ and increasing concentrations of the chelating agent EGTA (i.e. inactivation curve). Different results were obtained for the activation and inactivation curves. The inactivation curve showed that PEPCK activity was almost unaffected by variations of the free Mn2+ concentration over the range 0.05-0.15 microM. Under comparable experimental conditions, rat liver arginase (another Mn(2+)-dependent enzyme) was completely inactivated. From kinetic evidence, the existence of two distinct molecular forms of cytosolic rat liver PEPCK with different Mn2+ affinities is postulated. Considering the high affinity of PEPCK for Mn2+ and its relative insensitivity to changes in the free Mn2+ concentration, it seems rather unlikely that changes in the free cation concentration play a major role in regulating PEPCK activity in vivo.

scholarly journals Control of the redox state of the nicotinamide–adenine dinucleotide couple in rat liver cytoplasm

1972 ◽  
Vol 126 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Marion Stubbs ◽  
R. L. Veech ◽  
H. A. Krebs
Keyword(s):  
Rat Liver ◽  
Redox State ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Phosphoglycerate Kinase ◽  
Phosphorylation State ◽  
Crotyl Alcohol ◽  
Order Of Magnitude ◽  
The Individual

1. A study has been made of the ability of rat liver in vivo to maintain equilibrium in the combined glyceraldehyde 3-phosphate dehydrogenase, 3-phosphoglycerate kinase and lactate dehydrogenase reactions, i.e. in the system: [Formula: see text] Attempts were made to upset equilibrium. The [lactate]/[pyruvate] ratio was rapidly changed by injection of ethanol or crotyl alcohol, and the value of [ATP]/[ADP][HPO42-] was rapidly changed by injection of ethionine or carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. 2. The concentrations of the metabolites occurring in the above equation were measured in freeze-clamped liver. 3. Although the injected agents caused large changes in the concentrations of the individual components, near-equilibrium in the system was maintained, as indicated by the fact that the value of [ATP]/[ADP][HPO42-], referred to as the phosphorylation state of the adenine nucleotides, measured directly agreed with the value calculated for equilibrium conditions from the above equation. 4. The results are discussed and taken to confirm that the order of magnitude of the value of the redox state of the cytoplasmic NAD couple in rat liver is controlled by the phosphorylation state of the adenine nucleotide system.

scholarly journals Precocious development of uridine diphosphate glucuronosyltransferase activity during organ culture of foetal rat liver in the presence of glucocorticoids

1977 ◽  
Vol 166 (2) ◽  
pp. 249-253 ◽  
Author(s):  
G J Wishart ◽  
M A Goheer ◽  
J E A Leakey ◽  
G J Dutton
Keyword(s):  
Rat Liver ◽  
Defined Medium ◽  
Transferase Activity ◽  
Uridine Diphosphate ◽  
Chemically Defined Medium ◽  
Foetal Rat ◽  
First Time ◽  
Precocious Development ◽  
Stimulation Of

1. Precocious development of mammalian UDP-glucuronosyltransferase (EC 2.4.1.1.7) induced by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs in cultured explants of foetal rat liver when exposed to corticosteroids possessing a pregn-4′-ene structure and a hydroxy or an oxo group at C-11. 3. Explants from 14-day foetuses cultured for 3 days in a chemically defined medium containing dexamethasone exhibited transferase activities towards o-aminophenol within adult male values. Those liver transferase activities attained in utero by 17 days were still negligible. 4. Evidence from several approaches indicated that the explants required glucocorticoids for expression of the transferase, not for maintenance of viability. 5. Glucocorticoid-dependent stimulation of transferase activity required incorporation of L-[14C]leucine into protein, as judged from the pulsing of cultures with cycloheximide. 6. The relevance of these culture experiments to the situation in vivo is discussed.

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