Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation

T. Kagimoto; K. Uyeda

doi:10.1016/0003-9861(80)90240-4

Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation

T. Kagimoto, K. Uyeda

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Abstract

In perfused rat liver, the effects of various hormones on the stimulation of phosphorylation and allosteric properties of purified phosphorfructokinase were investigated. Rat livers were perfused with [³²P]phosphate followed with various hormones or cyclicAMP, and ³²P-labeled phosphofructokinase was isolated. ³²P incorporation into the enzyme and enzyme inhibition by ATP or citrate were determined. Only glucagon increased the ³²P incorporation into phosphofructokinase and this increase was approximately threefold. The cyclicAMP level was increased simultaneously approximately four- to fivefold compared to the control perfused liver. Similar results were obtained by perfusing the liver with cyclicAMP (0.1 mm). The phosphorylated phosphofructokinase showed a decrease in the K_i values for ATP (from 0.4 to 0.2 mm) and citrate (from 2 to 0.6 mm). Neither epinephrine nor insulin affected the extent of phosphorylation or the allosteric properties of the enzyme. The half-maximal concentration of glucagon required for phosphorylation of phosphofructokinase and modification of its allosteric properties was approximately 6 × 10⁻¹¹m. It is concluded that glucagon increases the inhibition of liver phosphofructokinase by ATP and citrate through phosphorylation of the enzyme involving a β-receptor-mediated cyclicAMP-dependent mechanism.

Original language	English (US)
Pages (from-to)	792-799
Number of pages	8
Journal	Archives of Biochemistry and Biophysics
Volume	203
Issue number	2
DOIs	https://doi.org/10.1016/0003-9861(80)90240-4
State	Published - 1980

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/0003-9861(80)90240-4

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@article{84fd52b73ff74b319dfe5564c3fffdb8,

title = "Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation",

abstract = "In perfused rat liver, the effects of various hormones on the stimulation of phosphorylation and allosteric properties of purified phosphorfructokinase were investigated. Rat livers were perfused with [32P]phosphate followed with various hormones or cyclicAMP, and 32P-labeled phosphofructokinase was isolated. 32P incorporation into the enzyme and enzyme inhibition by ATP or citrate were determined. Only glucagon increased the 32P incorporation into phosphofructokinase and this increase was approximately threefold. The cyclicAMP level was increased simultaneously approximately four- to fivefold compared to the control perfused liver. Similar results were obtained by perfusing the liver with cyclicAMP (0.1 mm). The phosphorylated phosphofructokinase showed a decrease in the Ki values for ATP (from 0.4 to 0.2 mm) and citrate (from 2 to 0.6 mm). Neither epinephrine nor insulin affected the extent of phosphorylation or the allosteric properties of the enzyme. The half-maximal concentration of glucagon required for phosphorylation of phosphofructokinase and modification of its allosteric properties was approximately 6 × 10−11m. It is concluded that glucagon increases the inhibition of liver phosphofructokinase by ATP and citrate through phosphorylation of the enzyme involving a β-receptor-mediated cyclicAMP-dependent mechanism.",

author = "T. Kagimoto and K. Uyeda",

note = "Funding Information: Studies by various investigators indicate that glucagon stimulates the early steps of gluconeogenesis (1, 2) and inhibits glycolysis (3-6). Although the exact mechanism of this glucagon action has not been elucidated, an attractive possibility is that this hormone action involved phosphorylation of a key enzyme(s) of glycolysis which results in the inhibition of the enzyme(s). Within the past few years it has been demonstrated that glucagon stimulates phosphorylation of pyruvate kinase (7-ll), one of the regulatory enzymes of glycolysis, which results in decreased enzyme activity (12, 13). Liver phosphofructokinase has also been shown to be phosphorylated in vitro by L This work was supported by the Veterans Administration and by National Institutes of Health Grant AM-16194. 2 Permanent address: Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan. 3 To whom all correspondence should be sent at the Pre-Clinical Science Unit, Veterans Administration Medical Center.",

year = "1980",

doi = "10.1016/0003-9861(80)90240-4",

language = "English (US)",

volume = "203",

pages = "792--799",

journal = "Archives of Biochemistry and Biophysics",

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T1 - Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation

AU - Kagimoto, T.

AU - Uyeda, K.

N1 - Funding Information: Studies by various investigators indicate that glucagon stimulates the early steps of gluconeogenesis (1, 2) and inhibits glycolysis (3-6). Although the exact mechanism of this glucagon action has not been elucidated, an attractive possibility is that this hormone action involved phosphorylation of a key enzyme(s) of glycolysis which results in the inhibition of the enzyme(s). Within the past few years it has been demonstrated that glucagon stimulates phosphorylation of pyruvate kinase (7-ll), one of the regulatory enzymes of glycolysis, which results in decreased enzyme activity (12, 13). Liver phosphofructokinase has also been shown to be phosphorylated in vitro by L This work was supported by the Veterans Administration and by National Institutes of Health Grant AM-16194. 2 Permanent address: Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan. 3 To whom all correspondence should be sent at the Pre-Clinical Science Unit, Veterans Administration Medical Center.

PY - 1980

Y1 - 1980

N2 - In perfused rat liver, the effects of various hormones on the stimulation of phosphorylation and allosteric properties of purified phosphorfructokinase were investigated. Rat livers were perfused with [32P]phosphate followed with various hormones or cyclicAMP, and 32P-labeled phosphofructokinase was isolated. 32P incorporation into the enzyme and enzyme inhibition by ATP or citrate were determined. Only glucagon increased the 32P incorporation into phosphofructokinase and this increase was approximately threefold. The cyclicAMP level was increased simultaneously approximately four- to fivefold compared to the control perfused liver. Similar results were obtained by perfusing the liver with cyclicAMP (0.1 mm). The phosphorylated phosphofructokinase showed a decrease in the Ki values for ATP (from 0.4 to 0.2 mm) and citrate (from 2 to 0.6 mm). Neither epinephrine nor insulin affected the extent of phosphorylation or the allosteric properties of the enzyme. The half-maximal concentration of glucagon required for phosphorylation of phosphofructokinase and modification of its allosteric properties was approximately 6 × 10−11m. It is concluded that glucagon increases the inhibition of liver phosphofructokinase by ATP and citrate through phosphorylation of the enzyme involving a β-receptor-mediated cyclicAMP-dependent mechanism.

AB - In perfused rat liver, the effects of various hormones on the stimulation of phosphorylation and allosteric properties of purified phosphorfructokinase were investigated. Rat livers were perfused with [32P]phosphate followed with various hormones or cyclicAMP, and 32P-labeled phosphofructokinase was isolated. 32P incorporation into the enzyme and enzyme inhibition by ATP or citrate were determined. Only glucagon increased the 32P incorporation into phosphofructokinase and this increase was approximately threefold. The cyclicAMP level was increased simultaneously approximately four- to fivefold compared to the control perfused liver. Similar results were obtained by perfusing the liver with cyclicAMP (0.1 mm). The phosphorylated phosphofructokinase showed a decrease in the Ki values for ATP (from 0.4 to 0.2 mm) and citrate (from 2 to 0.6 mm). Neither epinephrine nor insulin affected the extent of phosphorylation or the allosteric properties of the enzyme. The half-maximal concentration of glucagon required for phosphorylation of phosphofructokinase and modification of its allosteric properties was approximately 6 × 10−11m. It is concluded that glucagon increases the inhibition of liver phosphofructokinase by ATP and citrate through phosphorylation of the enzyme involving a β-receptor-mediated cyclicAMP-dependent mechanism.

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DO - 10.1016/0003-9861(80)90240-4

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JO - Archives of Biochemistry and Biophysics

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ER -

Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation

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