Effect of Endotoxin on Pyruvate Kinase Activity in Mouse Liver

Snyder, Irvin S.; Deters, Michael; Ingle, James N.

doi:10.1128/iai.4.2.138-142.1971

Cited by 21 publications

(19 citation statements)

References 16 publications

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“…Thus, endotoxin does not inhibit the synthetic process leading to TAT production. At the same time that PEPCK is inhibited by endotoxin and TAT remains unchanged, the activity of some enzymes involved in the glycolytic pathway is enhanced (13). This seems to rule out the idea that the effect of endotoxin on PEPCK is merely a symptom of a loss of general metabolic control within the cell.…”

Section: Methodsmentioning

confidence: 99%

Study of Inhibition of Induction of Phosphoenolpyruvate Carboxykinase by Endotoxin with Radial Immunodiffusion

Rippe

Berry

1972

Infect Immun

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Phosphoenolpyruvate carboxykinase (PEPCK) was precipitated from supernatant fluids of whole mouse liver homogenates by specific antiserum but not by normal rabbit immunoglobulin G. The slopes of inactivation curves were similar for supernatant fluids of control and poisoned mice. It was demonstrated by radial immunodiffusion that PEPCK activity assayed enzymatically was proportional to the diameter of precipitin rings in all cases, except when the enzyme was activated by tryptophan, a process not requiring new enzyme synthesis. Hence, the assay can be used to distinguish between enhanced catalytic activity due to increased enzyme levels or as the result of activation of existing enzyme molecules. Immunological quantitation of PEPCK showed that endotoxin inhibits the induction of the enzyme due to fasting between 4 and 8 hr after administration of the bacterial poison. This result is almost identical to that seen when livers of mice poisoned with actinomycin D were assayed for PEPCK by the radial immunodiffusion technique.

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Section: Methodsmentioning

confidence: 99%

Study of Inhibition of Induction of Phosphoenolpyruvate Carboxykinase by Endotoxin with Radial Immunodiffusion

Rippe

Berry

1972

Infect Immun

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“…These results are consistent with the idea that the inhibition of gluconeogenesis and increased glycolytic carbon flow in liver cells from endotoxic animals are caused by a stimulation of flux through PFK-1, and not of flux through glucokinase. Snyder and co-workers have proposed a role for increases in pyruvate kinase activity in the inhibition of glucose synthesis [14,15]. Three lines of evidence suggest that this is not the mechanism of the inhibition of Vol.…”

Section: Site Of Inhibition Of Gluconeogenesis By Endotoxinmentioning

confidence: 99%

“…Endotoxin is known to decrease the activity of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) in the livers of mice by antagonizing its induction by glucocorticoids (reviewed in [11]). Because of the important regulatory role postulated for PEPCK in gluconeogenesis [12,13], it has been inferred that this decrease in PEPCK by endotoxin is the primary cause of the inhibition of gluconeogenesis; a role for increases in pyruvate kinase activity has, however, also been suggested [14,15].…”

Section: Introductionmentioning

confidence: 99%

The characteristics and site of inhibition of gluconeogenesis in rat liver cells by bacterial endotoxin. Stimulation of phosphofructokinase-1

Knowles¹,

McCabe²,

Beevers³

et al. 1987

Biochemical Journal

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The characteristics and site of inhibition of gluconeogenesis by endotoxin were investigated in liver cells isolated from control and endotoxin-treated rats. Endotoxin treatment was associated with inhibition (40-50%) of gluconeogenesis from lactate plus pyruvate over a range of concentrations of substrate and of oleate and with or without glucose or glucagon. Similar inhibition was observed with asparagine, proline, glutamine, alanine and a substrate mixture, but not with glycerol, glyceraldehyde, dihydroxyacetone or endogenous substrates. There was no change in cellular ATP content or in the rates of ketogenesis or ureogenesis from asparagine, proline or glutamine. Other effects on isotopic fluxes, metabolite contents, enzyme activities and control coefficients were consistent with the suggestion that the effects of endotoxin on gluconeogenesis are exerted at the level of phosphofructokinase-1, and not at phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate carboxylase or glucokinase.

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“…Animals injected with endotoxin initially exhibited a hyperglycemia, then declined into a hypoglycemia with a concomitant decrease in hepatic and muscular glycogen postintoxication. It has been reported (4,30,41) that the glycogen depletion and the hypoglycemia were associated with changes in activities of enzymes involved in glycogen synthesis and glucose metabolism. Many workers (15,43,44) have suggested that gluconeogenesis was impaired by the administration of endotoxin.…”

mentioning

confidence: 99%