Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of the commonly used anesthetic pentobarbital to hepatocytes from fed rats resulted in a dose-dependent decrease in the level of fructose 2,6-bisphosphate. At a concentration of pentobarbital (0.4 mM) that lowered fructose 2,6-bisphosphate by 60%, there was no significant change in the level of fructose 6-phosphate, ATP, or L-glycerol 3-phosphate. Higher concentrations of pentobarbital (2 mM) enhanced both glycolysis and glycogenolysis and fructose 2,6-bisphosphate levels were reduced to less than 10% of the control. Concomitant with these changes there was a decrease in ATP, glucose 6-phosphate, and fructose 6-phosphate and a two- and fivefold increase in ADP and AMP, respectively. In hepatocytes from starved rats pentobarbital also lowered ATP levels and inhibited gluconeogenesis but had no effect on either lactate production or the already low level of sugar diphosphate. However, in the fasted case pentobarbital completely prevented the 10-fold elevation of fructose 2,6-bisphosphate brought about by 30 mM glucose. The anesthetic had no effect on cAMP-dependent protein kinase activity or on pyruvate kinase activity in hepatocytes from fed or starved rats but caused reciprocal changes in the activities of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase. Kinase activity was decreased and bisphosphatase activity was increased. These results suggest that the effects of pentobarbital on gluconeogenesis and glycolysis are due to inhibition of energy metabolism with elevated AMP levels causing activation of 6-phosphofructo-1-kinase and inhibition of fructose 1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of pentobarbital on fructose 2,6-bisphosphate metabolism in isolated rat hepatocytes. 299 99

The addition of beta-D-glucose (final concentration, 50 mM) to a cell suspension of Saccharomyces cerevisiae in stationary phase caused a rapid 4-fold increase in the concentration of cAMP, while a 2-fold increase of cAMP was observed by the addition of alpha-D-glucose. beta -D-Glucose was also more effective than alpha-D-glucose in the inactivation of fructose 1,6-bisphosphatase and the activation of trehalase. These results, taken together with the previous report that alpha-D-glucose is transported more rapidly than beta-D-glucose in Saccharomyces cerevisiae, do not support the view currently proposed by some investigators that cotransport of D-glucose with protons causes the depolarization of the cell membrane, resulting in the activation of adenylate cyclase. The present data, however, provides supporting evidence for the view that cAMP-dependent protein kinase is implicated in the inactivation of fructose 1,6-bisphosphatase and the activation of trehalase.
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PMID:Anomeric specificity of glucose effect on cAMP, fructose 1,6-bisphosphatase, and trehalase in yeast. 303 Mar 16

Acute hormonal regulation of liver carbohydrate metabolism mainly involves changes in the cytosolic levels of cAMP and Ca2+. Epinephrine, acting through beta 2-adrenergic receptors, and glucagon activate adenylate cyclase in the liver plasma membrane through a mechanism involving a guanine nucleotide-binding protein that is stimulatory to the enzyme. The resulting accumulation of cAMP leads to activation of cAMP-dependent protein kinase, which, in turn, phosphorylates many intracellular enzymes involved in the regulation of glycogen metabolism, gluconeogenesis, and glycolysis. These are (1) phosphorylase b kinase, which is activated and, in turn, phosphorylates and activates phosphorylase, the rate-limiting enzyme for glycogen breakdown; (2) glycogen synthase, which is inactivated and is rate-controlling for glycogen synthesis; (3) pyruvate kinase, which is inactivated and is an important regulatory enzyme for glycolysis; and (4) the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase bifunctional enzyme, phosphorylation of which leads to decreased formation of fructose 2,6-P2, which is an activator of 6-phosphofructo-1-kinase and an inhibitor of fructose 1,6-bisphosphatase, both of which are important regulatory enzymes for glycolysis and gluconeogenesis. In addition to rapid effects of glucagon and beta-adrenergic agonists to increase hepatic glucose output by stimulating glycogenolysis and gluconeogenesis and inhibiting glycogen synthesis and glycolysis, these agents produce longer-term stimulatory effects on gluconeogenesis through altered synthesis of certain enzymes of gluconeogenesis/glycolysis and amino acid metabolism. For example, P-enolpyruvate carboxykinase is induced through an effect at the level of transcription mediated by cAMP-dependent protein kinase. Tyrosine amino-transferase, serine dehydratase, tryptophan oxygenase, and glucokinase are also regulated by cAMP, in part at the level of specific messenger RNA synthesis. The sympathetic nervous system and its neurohumoral agonists epinephrine and norepinephrine also rapidly alter hepatic glycogen metabolism and gluconeogenesis acting through alpha 1-adrenergic receptors. The primary response to these agonists is the phosphodiesterase-mediated breakdown of the plasma membrane polyphosphoinositide phosphatidylinositol 4,5-P2 to inositol 1,4,5-P3 and 1,2-diacylglycerol. This involves a guanine nucleotide-binding protein that is different from those involved in the regulation of adenylate cyclase. Inositol 1,4,5-P3 acts as an intracellular messenger for Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of hormonal regulation of hepatic glucose metabolism. 303 41

Fructose 2,6-bisphosphate is a potent allosteric activator of 6-phosphofructo 1-kinase and an inhibitor of fructose 1,6-bisphosphatase. It potentiates the effect of AMP on both enzymes. A great deal of compelling evidence supports the hypothesis that fructose 2,6-bisphosphate plays a key role in the hormonal and substrate regulation of substrate cycling at the fructose 6-phosphate/fructose 1,6-bisphosphate level in liver. This regulation is exerted at the level of the enzyme activities responsible for the synthesis and degradation of fructose 2,6-bisphosphate. Synthesis of the compound is catalyzed by a unique enzyme which transfers the gamma-phosphate of ATP to the C2 position of fructose 6-phosphate (ATP:D fructose 6-phosphate 2-phosphotransferase) while degradation is catalyzed by a phosphohydrolase activity which is specific for the C-2 position of fructose 2,6-bisphosphate (D-fructose 2,6-bisphosphate 2-phosphohydrolase). These activities are distinct from the classical 6-phosphofructo 1-kinase and fructose 1,6-bisphosphatase with regard to molecular weight, interaction with ligands, and the efficiency with which phosphoryl transfer occurs. Both activities have been purified to homogeneity and have been shown to be present in a single enzyme protein, i.e. the enzyme is bifunctional. Incubation of the 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase with cAMP-dependent protein kinase and ATP leads to phosphorylation of the enzyme resulting in inactivation of the phosphotransferase activity and stimulation of the phosphohydrolase activity. Since fructose 2,6-bisphosphate is not further metabolized and can only be recycled to fructose 6-phosphate, simultaneous modulation of the synthesis and degradation of the compound by covalent modification of a single protein provides a very efficient and sensitive regulatory mechanism. The bifunctional enzyme was also shown to possess an ATPase activity which was nearly equal to the activity of the kinase reaction. However, in the presence of fructose 6-phosphate the enzyme did not transfer phosphate to water but rather to the C-2 position of the phosphorylated sugar. The ability of the enzyme to catalyze a partial reaction at a rate nearly equal to that of the forward reaction suggested that the reaction mechanism of the kinase proceeds by a two step transfer, i.e. via a phosphoryl enzyme intermediate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rat hepatic 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase: a unique bifunctional enzyme. 610 May 82

Fructose-1,6-bisphosphatase purified from Saccharomyces cerevisiae is phosphorylated in vitro by a cAMP-dependent protein kinase. The phosphorylation reaction incorporates 1 mol of phosphate/mol of enzyme and is greatly stimulated by fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate acts upon fructose-1,6-bisphosphatase, not on the protein kinase. The phosphorylation of fructose 1,6-bisphosphatase lowers its activity by about 50%. The characteristics of the phosphorylation reaction in vitro show that this modification is responsible for the inactivation of fructose-1,6-bisphosphatase observed in vivo.
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PMID:Fructose 2,6-bisphosphate activates the cAMP-dependent phosphorylation of yeast fructose-1,6-bisphosphatase in vitro. 630 22

Purified liver fructose 1,6-bisphosphatase exhibits different forms upon isoelectric focusing. The enzyme focused at pH 5.75, 5.60, and 5.44. Treatment of the enzyme preparation with the catalytic subunit of cAMP-dependent protein kinase and ATP altered the isoelectric focusing profile such that the bands at 5.75 and 5.60 were diminished, the band at 5.44 increased, and two new bands appeared at 5.30, and 5.18. Fructose 1,6-bisphosphatase may be present in rat liver in different forms, one of which is phosphorylated as the enzyme is isolated.
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PMID:Evidence for different forms of rat liver fructose 1,6-bisphosphatase. 632 Aug 15

A phosphoprotein phosphatase has been purified from rat liver cytosol. The purification involved chromatography on DEAE-cellulose. Sephacryl S-200, fast protein liquid chromatography (FPLC) and sucrose density gradient centrifugation. It resulted in an almost homogeneous enzyme with a relative molecular mass, Mr, of 90 000 by gel filtration and sucrose gradient centrifugation and Mr = 44 500 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). Therefore it seems to be a dimeric enzyme. This protein phosphatase (termed PFK-phosphatase) is completely dependent on Mg2+, which can be replaced partly by Mn2+. It can be eluted from DEAE-cellulose with 120 mM NaCl, is not affected by Ca2+, 100 microM trifluoperazine or the heat-stable inhibitor-2. Inhibition occurs with phosphate, ammonium sulfate and fluoride. PFK-phosphatase dephosphorylates preferentially the alpha subunit of phosphorylase kinase (alpha/beta dephosphorylation ratio 5-10). Phosphorylase a, mixed histone and casein do not serve as substrates. The enzyme dephosphorylates effectively the key enzymes of glucose metabolism 6-phosphofructo-1-kinase, fructose 1,6-bisphosphatase, pyruvate kinase and 6-phosphofructo-2-kinase. Using this protein phosphatase and the catalytic subunit of cAMP-dependent protein kinase, a complete phosphorylation, dephosphorylation and rephosphorylation cycle was possible with 6-phosphofructo-1-kinase as substrate.
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PMID:Purification and characterization of a protein phosphatase from rat liver acting on key enzymes of glucose metabolism. 632 87