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C I Pogson

Publications and source records attributed to C I Pogson.

At least 109 records · Page 6Linked to original sources

Inhibition of gluconeogenesis in isolated rat liver cells by methylenecyclopropylpyruvate (ketohypoglycin).

1. In isolated rat liver cells, hypoglycin is a less effective inhibitor of gluconeogenesis than its transamination product, methylenecyclopropylpyruvate (ketohypoglycin). 2. Methylenecyclopropylpyruvate at 0.3 mM inhibits gluconeogenesis from all substrates tested, except fructose. 3. Methylenecyclopropylpyruvate does not affect 14CO2 release from [1(-14)C]palmitate, but, in the absence of lactate, inhibits ketogenesis and causes a decrease in the [beta-hydroxybutyrate]/[acetoacetate] ratio. These effects are masked when lactate (10 mM) is present. 4. In the presence of lactate and palmitate, 0.3 mM-methylenecyclopropylpyruvate produces a fall in total acid-soluble CoA and a relative increase in short-chain acyl-CoA at the expense of CoA and acetyl-CoA without changing the ATP, ADP and aspartate contents or the [lactate]/[pyruvate] ratio. 5. Many of the effects of methylenecyclopropylpyruvate observed are consistent with inhibition of butyryl-CoA dehydrogenase and of specific CoA-dependent enzymes involved in gluconeogenesis.

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

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.

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Griseofulvin-induced aggregation of microtubule protein.

Griseofulvin (7-chloro-2',4,6-trimethoxy-6'-methylspiro[benzofuran-2(3H),1'-[2]cyclohexene]-3,4'-dione) induces aggregation of microtubule protein at 0 degrees C. This aggregate contains approx. 90% of the microtubule-associated proteins originally present in the microtubule protein. The supernatant obtained after removal of the griseofulvin-induced aggregate does not form microtubules on warming at 37 degrees C. Addition of the griseofulvin-aggregated protein to this supernatant and warming to 37 degrees C gives rise to a limited amount of microtubule assembly. The possible involvement of griseofulvin-induced aggregation of microtubule protein at 0 degrees C in the inhibition by griseofulvin of microtubule assembly in vitro is discussed.

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Preparation and characterization of isolated parenchymal cells from guinea pig liver.

1. A method is described for the preparation of isolated cells from guinea pig liver. This involved perfusion in situ, in the non-physiological direction, with collagenase. 2. The cell yield was 20--30%, comparable with those from the livers of other species. 3. The ratio of lactate dehydrogenase to glutamate dehydrogenase in the cells was similar to that in vivo, indicating that there was negligible leakage of cytoplasmic enzymes. 4. The concentrations of K+ and adenine nucleotides were initially lower than in the perfused liver; normal values were obtained on incubation, particularly in the presence of substrate. 5. The L-lactate: pyruvate ratio is 16:1, close to established values. The total beta-hydroxybutyrate: acetoacetate ratio indicates that the mitochondrial redox state is more oxidised than in the perfused liver, but the intracellular ratio is similar to that of the intact liver. 6. Rates of gluconeogenesis and ureogenesis, are within the physiological range. Maximal gluconeogeneis from L-lactate was preceded by a lag period. L-lysine stimulated glucose production from L-lactate but did not abolish the lag phase. 7. The effects of aminooxyacetate and octanoate on L-lactate gluconeogenesis were similar to those in the perfused liver.

Adenine Nucleotides↗

The effects of starvation and experimental diabetes on phosphoenol-pyruvate carboxykinase in the guinea pig.

1. Approx. 85% of liver phosphoenolpyruvate carboxykinase is associated with the mitochondrial fraction in the fed guinea pig. Enzyme activity is unchanged in diabetes, but doubles during starvation. In contrast with earlier reports, both cytoplasmic and mitochondrial activities were found to be increased. 2. In kidney cortex, total enzyme activity is increased in both starved and diabetic animals. These changes are associated with increases in the cytoplasmic activity alone. 3. In diabetic animals the mean blood-glucose concentration was 23.1 mM. Other blood metabolites were lower than those in the rat, and the animals did not show significant ketosis. 4. Changes in the rates of gluconeogenesis from lactate and propionate paralleled those in phosphoenolpyruvate carboxykinase activity.

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Permeability of the liver cell membrane to quinolinate.

Quinolinate was taken up by both rat and guinea-pig liver cells. Equilibrium was reached after approx. 20 min with rat cells, but guinea-pig cells had not achieved a steady state after 60 min. There was no evidence to suggest that quinolinate is rapidly metabolized by either species. The concentrations of quinolinate attained in rat and guinea-pig cells after short periods of incubation with 0.5 mM-quinolinate did not inhibit gluconeogenesis. These results raise further doubts as to the mechanism of quinolinate action in liver.

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Preparation and biochemical characterisation of isolated parenchymal cells from adult sheep liver.

1. A simple procedure for the isolation of morphologically intact, metabolically viable sheep liver parenchymal cells is described in detail. 2. The method is based on the initial treatment of fresh liver slices with collagenase and hyaluronidase. 3. The cell preparation was studied with respect to membrane permeability, potassium content, ATP/ADP ratio, adenylate content, and gluconeogenic capacity with respect to various substrates. 4. Data are present with respect to the distribution of phosphoenolpyruvate carboxykinase in isolated cells and whole sheep liver. 5. The results are compared, where possible, with data currently available from isolated perfused sheep liver and multi-catheterised animals.

Adenine Nucleotides↗