Inactivation of phosphofructokinase by glucagon in rat hepatocytes.
TL;DR: Phosphofructokinase inactivation by glucagon parallels the known inactivation of pyruvate kinase L and activation of glycogen phosphorylase alpha and exogenous cyclic AMP mimics the effect of this hormone.
About: This article is published in Journal of Biological Chemistry.The article was published on 1979-07-10 and is currently open access. It has received 124 citations till now. The article focuses on the topics: Phosphofructokinase & Glycogen phosphorylase.
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TL;DR: As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans and has been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.
Abstract: As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Compared with healthy subjects, diabetic patients and animals have abnormal secretion of not only insulin but also glucagon. Hyperglucagonemia and altered insulin-to-glucagon ratios play important roles in initiating and maintaining pathological hyperglycemic states. Not surprisingly, glucagon and glucagon receptor have been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.
797 citations
Cites background from "Inactivation of phosphofructokinase..."
...By reducing F(2,6)P2 levels as described above in Inhibition of glycogenesis, glucagon inhibits FPK1 activity and therefore inhibits glycolysis (16, 89)....
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TL;DR: The alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase and glucose-6-phosphate and phosphofructokinase levels in diabetic mice were partially restored by EJ but not by TC, and the mechanism of action of EJ and TC is discussed.
433 citations
TL;DR: Fru-2,6-P2 is not an intermediary metabolite of glycolysis, but its most potent regulator and its potential role in the control of metabolism in various organisms is delineated.
Abstract: It was in 1909 that Young, in the laboratory of Harden, isolated from fermenting yeast the fructose bisphosphate (the Harden and Young ester) that was later identified by Levene & Raymond (1928) as fructose 1,6-bisphosphate. Some 71 years elapsed until a second fructose bisphosphate was isolated from living cells and identified as fructose 2,6bisphosphate (Van Schaftingen et al., 1980c). In contrast with its elder brother, Fru-2,6-P2 is not an intermediary metabolite of glycolysis, but its most potent regulator. In the present review, we will summarize the work that led to its discovery and we will try to delineate its potential role in the control of metabolism in various organisms.
396 citations
293 citations
TL;DR: The low-molecular-weight stimulator of phosphofructokinase has been purified from rat liver and is tentatively identified as fructose 2,6-bisphosphate.
Abstract: The low-molecular-weight stimulator of phosphofructokinase [Van Schaftingen, Hue & Hers (1980) Biochem. J. 192, 887-895] has been purified from rat liver. It was completely destroyed upon incubation with 0.01 M-HCl for 10 min at 20 degrees C and fructose 6-phosphate and a reducing power equivalent in amount to the acid-labile organic phosphate were formed. It was therefore tentatively identified as fructose 2,6-bisphosphate.
292 citations
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TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: Cytoplasmic vacuolization in a small percentage of cells and potassium loss are the only indications of cell injury detected, and the isolated cells are comparable to normal hepatic parenchymal cells in situ in appearance and function.
Abstract: A new technique employing continuous recirculating perfusion of the rat liver in situ, shaking of the liver in buffer in vitro, and filtration of the tissue through nylon mesh, results in the conversion of about 50% of the liver into intact, isolated parenchymal cells. The perfusion media consist of: (a) calcium-free Hanks' solution containing 0.05% collagenase and 0.10% hyaluronidase, and (b) magnesium and calcium-free Hanks' solution containing 2 mM ethylenediaminetetraacetate. Biochemical and morphologic studies indicate that the isolated cells are viable. They respire in a medium containing calcium ions, synthesize glucose from lactate, are impermeable to inulin, do not stain with trypan blue, and retain their structural integrity. Electron microscopy of biopsies taken during and after perfusion reveals that desmosomes are quickly cleaved. Hemidesmosome-containing areas of the cell membrane invaginate and appear to pinch off and migrate centrally. Tight and gap junctions, however, persist on the intact, isolated cells, retaining small segments of cytoplasm from formerly apposing parenchymal cells. Cells which do not retain tight and gap junctions display swelling of Golgi vacuoles and vacuoles in the peripheral cytoplasm. Cytoplasmic vacuolization in a small percentage of cells and potassium loss are the only indications of cell injury detected. By other parameters measured, the isolated cells are comparable to normal hepatic parenchymal cells in situ in appearance and function.
4,183 citations
TL;DR: In this paper, auffindung des weges is studied, auf dem im tierischen Organismus die Synthese des Harnstoffs aus Ammoniak and Kohlensaure verlauft.
Abstract: Das Hauptergebnis dieser Arbeit ist die Auffindung des Weges, auf dem im tierischen Organismus die Synthese des Harnstoffs aus Ammoniak und Kohlensaure verlauft. Die Harnstoffsynthese ist an das Vorhandensein von Ornithin gebunden, ohne das Ornithin in der Bilanz der Synthese verbraucht wird. Ornithin, Ammoniak und Kohlensaure treten unter Wasseraustritt zu einer Guanidinoverbindung — dem Arginin — zusammen [Reaktion (1)]. Arginin spaltet durch die Wirkungder Arginase Harnstoffab [Reaktion (2)] und liefert Ornithin zuruck, das wieder fur Reaktion (1) zur Verfugung steht.
2,873 citations
TL;DR: In the isolated perfused rat liver, increasing glucose concentration from 5.5 to 55 mm in the perfusion medium caused a sequential inactivation of glycogen phosphorylase and activation of carbohydrate synthetase and in isolated hepatocytes, the rate of conversion of glucose into glycogen was propotional to the activity of synthet enzyme a in the preparation.
Abstract: In the isolated perfused rat liver, increasing glucose concentration from 5.5 to 55 mm in the perfusion medium caused a sequential inactivation of glycogen phosphorylase and activation of glycogen synthetase. The latter change was preceded by a lag period which corresponded to the time required to inactivate the major part of the phosphorylase. 2. The same sequence of events was observed in isolated rat hepatocytes incubated at 37C. In this preparation, the rate of phosphorylase inactivation was greatly increased by increasing the concentration of glucose and/or of K+ ions in the external medium. The same agents also caused the activation of glycogen synthetase, but this effect was secondary to the inactivation of phosphorylase. 3. In both types of preparations, the rate of synthetase activation was modulated by the residual amount of phosphorylase a that remained after the initial phase of rapid inactivation and was independent of glucose concentration. 4. In isolated hepatocytes, the rate of conversion of glucose into glycogen was propotional to the activity of synthetase a in the preparation. This conversion was preceded by a lag period which could be shortened by increasing either glucose or K+ concentration in the medium. The incorporation of labelled glucose into glycogen was simultaneous with a glycogenolytic process which could not be attributed to the activity of phosphorylase a.
313 citations
TL;DR: Methods are described that allow the determination of liver phosphorylase a without interference of b, and the determination in rat liver, which is influenced by anions and by AMP, and these effects are influenced by pH.
Abstract: 1
The activity of liver phosphorylase b from several mammalian species has been studied. The enzyme from rat or mouse has a higher activity than the rabbit enzyme, which is itself more active than pig liver phosphorylase b.
2
The activity of liver phosphorylase b is influenced by anions and by AMP, and these effects are influenced by pH. Fluoride, which is currently added to the assay mixture of phosphorylase a in crude preparations, is about as active as sulfate as a stimulator of phosphorylase b.
3
When assayed at pH 6.1 and in the presence of 0.15 M NaF, the activity of rat liver phosphorylase b reaches 25% of that of the a enzyme; if 1 mM AMP is also present, this value rises to 50%.
4
Methods are described that allow the determination of liver phosphorylase a without interference of b, and the determination of total phosphorylase (a+b) in rat liver.
282 citations