In isolated perfused rat hearts, the half-maximal AMPK activation (A0.5) was 1.8 ± 0.3 μM AMP despite high [ATP], suggesting reduced ATP antagonism of AMPK activation in vivo.
The study demonstrates that in the intact rat heart, AMPK is activated at low AMP concentrations despite high ATP levels, suggesting reduced ATP antagonism in vivo compared to in vitro models.
The objective of this study was to define the relationship among AMP-activated protein kinase (AMPK) activity, AMP concentration (AMP), and ATP in perfused rat hearts. Bromo-octanoate, an inhibitor of β-oxidation, and amino-oxyacetate, an inhibitor of the malate-aspartate shuttle, were used to modify substrate flux and thus increase cytosolic AMP. Cytosolic AMP was calculated using metabolites measured by 31P NMR spectroscopy. Rat hearts were perfused with Krebs-Henseleit solution containing glucose and either no inhibitor, the inhibitors, or the inhibitors plus butyrate, a substrate that bypasses the metabolic blocks. In this way, AMP changed from 0.2 to 27.9 μm, and ATP varied between 11.7 and 6.8 mm. AMPK activity ranged from 7 to 60 pmol·min−1·μg of protein−1. The half-maximal AMPK activation (A0.5) was 1.8 ± 0.3 μmAMP. Measurements in vitro have reported similar AMPKA0.5 at 0.2 mm ATP, but found thatA0.5 increased 10–20-fold at 4 mmATP. The low A0.5 of this study despite a high ATP suggests that in vivo the ATP antagonism of AMPK activation is reduced, and/or other factors besides AMP activate AMPK in the heart. The objective of this study was to define the relationship among AMP-activated protein kinase (AMPK) activity, AMP concentration (AMP), and ATP in perfused rat hearts. Bromo-octanoate, an inhibitor of β-oxidation, and amino-oxyacetate, an inhibitor of the malate-aspartate shuttle, were used to modify substrate flux and thus increase cytosolic AMP. Cytosolic AMP was calculated using metabolites measured by 31P NMR spectroscopy. Rat hearts were perfused with Krebs-Henseleit solution containing glucose and either no inhibitor, the inhibitors, or the inhibitors plus butyrate, a substrate that bypasses the metabolic blocks. In this way, AMP changed from 0.2 to 27.9 μm, and ATP varied between 11.7 and 6.8 mm. AMPK activity ranged from 7 to 60 pmol·min−1·μg of protein−1. The half-maximal AMPK activation (A0.5) was 1.8 ± 0.3 μmAMP. Measurements in vitro have reported similar AMPKA0.5 at 0.2 mm ATP, but found thatA0.5 increased 10–20-fold at 4 mmATP. The low A0.5 of this study despite a high ATP suggests that in vivo the ATP antagonism of AMPK activation is reduced, and/or other factors besides AMP activate AMPK in the heart. AMP-activated protein kinase acetyl-CoA-carboxylase bromo-octanoate amino-oxyacetate phosphocreatine intracellular pH Krebs-Henseleit buffer phenylphosphonic acid beats/min AMP-activated protein kinase (AMPK)1 and AMPK kinase comprise a protein kinase cascade that has been highly conserved throughout evolution (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref D.G. Carling D. Biochem. in AMP concentration activate this cascade by Carling D. D.G. J. D.G. D.G. Eur. J. Biochem. an activation by AMP of AMPK the of AMP to a substrate protein the of AMP to AMPK a substrate AMPK and the activation by AMP of The of AMP by high of the AMPK is AMP is and ATP is AMPK is to (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref AMPK in to metabolic AMPK to activation of to increase ATP and of to ATP AMPK acetyl-CoA-carboxylase activity, the J. 1997; Biochem. J. of acid the acid by the ATP In and AMPK activity glucose by J. In AMPK of a of J. Carling D. AMPK and acid D.G. J. D. J. J. 1997; have the relationship between the activation of AMPK and AMP. D.G. Biochem. J. the AMPK a of AMPK activity to AMP with a half-maximal activation (A0.5) of 4 measured AMPK activity of the and in vitro a of AMP Carling D. Biochem. J. a increase in AMPK activity with with an A0.5 of and In J. Carling D. reported a relationship between AMPK activity and using AMP measured in of rat hearts or with inhibitors of ATP of the study was to define the relationship between AMPK activation and cytosolic AMP in vivo in the perfused rat heart. an that substrate by of the inhibitors bromo-octanoate to acid and amino-oxyacetate to J. J. this with increased the phosphocreatine J. 1997; used 31P NMR to the and ATP the intracellular pH of hearts. The kinase and the kinase were used to and The of is an increase in AMP with a Cytosolic AMP was in a and the AMPK activity was in this define the relationship between AMPK activity and the cytosolic AMP in the perfused rat heart. this is the of AMPK activity with cytosolic AMP in the heart. increase the cytosolic AMP in perfused rat the of was using the inhibitors bromo-octanoate and and high J. 1997; of the of the kinase the of in an increase in In the of the kinase the increase in an increase in AMP. 31P ATP, and an of cytosolic AMP in from the AMPK activity and AMP of the of hearts and glucose and low of AMP and AMPK AMPK activity in hearts with inhibitors of acid and glucose but with the substrate butyrate, the of β-oxidation, is to that of the hearts. hearts AMP to of hearts. that AMPK activity increase to of the AMPK activity increased in the hearts at hearts with and to acid and glucose have increased AMP increased AMPK In this hearts with an AMP AMPK activity in AMPK activity have been reported by a of In vitro by found a activity the AMPK and a activity the AMPK Carling D. Biochem. J. The AMPK with the of the D. J. J. D.G. Eur. J. Biochem. J. reported a increase in AMPK activity in the of study by J. Carling D. of AMPK activity found a increase of to a increase of In the the increase in AMPK activity was to AMPK activity the that in this study measured AMPK activity of The AMPK activity, pmol·min−1·μg of is an increase of the the AMPK activity of was the activity in the of this The AMPK activity in the from activation to AMP. in the rat AMP is at to in to Cytosolic AMP to and is at a of J. of AMP to to of J. The in the study in but is AMP the AMPK activity and AMPK to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. and the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 and AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the and activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the of ATP, and by 31P NMR the of cytosolic AMP to in the of 1.8 is with the A0.5 measured in vitro in the of 0.2 mm In the AMPK A0.5 increased 10–20-fold at 4 mm ATP to the of ATP the AMP activation of In the ATP 7 mm. The in the of 7 mm ATP in the suggests of AMPK in the ATP antagonism of AMPK activation is AMPK an ATP that is the cytosolic or factors in to AMP activate AMPK in the heart. to AMP-activated protein kinase (AMPK)1 and AMPK kinase comprise a protein kinase cascade that has been highly conserved throughout evolution (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref D.G. Carling D. Biochem. in AMP concentration activate this cascade by Carling D. D.G. J. D.G. D.G. Eur. J. Biochem. an activation by AMP of AMPK the of AMP to a substrate protein the of AMP to AMPK a substrate AMPK and the activation by AMP of The of AMP by high of the AMPK is AMP is and ATP is AMPK is to (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref AMPK in to metabolic AMPK to activation of to increase ATP and of to ATP AMPK acetyl-CoA-carboxylase activity, the J. 1997; Biochem. J. of acid the acid by the ATP In and AMPK activity glucose by J. In AMPK of a of J. Carling D. AMPK and acid D.G. J. D. J. J. 1997; have the relationship between the activation of AMPK and AMP. D.G. Biochem. J. the AMPK a of AMPK activity to AMP with a half-maximal activation (A0.5) of 4 measured AMPK activity of the and in vitro a of AMP Carling D. Biochem. J. a increase in AMPK activity with with an A0.5 of and In J. Carling D. reported a relationship between AMPK activity and using AMP measured in of rat hearts or with inhibitors of ATP The of the study was to define the relationship between AMPK activation and cytosolic AMP in vivo in the perfused rat heart. an that substrate by of the inhibitors bromo-octanoate to acid and amino-oxyacetate to J. J. this with increased the phosphocreatine J. 1997; used 31P NMR to the and ATP the intracellular pH of hearts. The kinase and the kinase were used to and The of is an increase in AMP with a Cytosolic AMP was in a and the AMPK activity was in this define the relationship between AMPK activity and the cytosolic AMP in the perfused rat heart. this is the of AMPK activity with cytosolic AMP in the heart. increase the cytosolic AMP in perfused rat the of was using the inhibitors bromo-octanoate and and high J. 1997; of the of the kinase the of in an increase in In the of the kinase the increase in an increase in AMP. 31P ATP, and an of cytosolic AMP in from the AMPK activity and AMP of the of hearts and glucose and low of AMP and AMPK AMPK activity in hearts with inhibitors of acid and glucose but with the substrate butyrate, the of β-oxidation, is to that of the hearts. hearts AMP to of hearts. that AMPK activity increase to of the AMPK activity increased in the hearts at hearts with and to acid and glucose have increased AMP increased AMPK In this hearts with an AMP AMPK activity in AMPK activity have been reported by a of In vitro by found a activity the AMPK and a activity the AMPK Carling D. Biochem. J. The AMPK with the of the D. J. J. D.G. Eur. J. Biochem. J. reported a increase in AMPK activity in the of study by J. Carling D. of AMPK activity found a increase of to a increase of In the the increase in AMPK activity was to AMPK activity the that in this study measured AMPK activity of The AMPK activity, pmol·min−1·μg of is an increase of the the AMPK activity of was the activity in the of this The AMPK activity in the from activation to AMP. in the rat AMP is at to in to Cytosolic AMP to and is at a of J. of AMP to to of J. The in the study in but is AMP the AMPK activity and AMPK to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. and the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 and AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the and activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the of ATP, and by 31P NMR the of cytosolic AMP to in the of 1.8 is with the A0.5 measured in vitro in the of 0.2 mm In the AMPK A0.5 increased 10–20-fold at 4 mm ATP to the of ATP the AMP activation of In the ATP 7 mm. The in the of 7 mm ATP in the suggests of AMPK in the ATP antagonism of AMPK activation is AMPK an ATP that is the cytosolic or factors in to AMP activate AMPK in the heart. to in this define the relationship between AMPK activity and the cytosolic AMP in the perfused rat heart. this is the of AMPK activity with cytosolic AMP in the heart. increase the cytosolic AMP in perfused rat the of was using the inhibitors bromo-octanoate and and high J. 1997; of the of the kinase the of in an increase in In the of the kinase the increase in an increase in AMP. 31P ATP, and an of cytosolic AMP in from the AMPK activity and AMP of the of hearts and glucose and low of AMP and AMPK AMPK activity in hearts with inhibitors of acid and glucose but with the substrate butyrate, the of β-oxidation, is to that of the hearts. hearts AMP to of hearts. that AMPK activity increase to of the AMPK activity increased in the hearts at hearts with and to acid and glucose have increased AMP increased AMPK In this hearts with an AMP AMPK activity in AMPK activity have been reported by a of In vitro by found a activity the AMPK and a activity the AMPK Carling D. Biochem. J. The AMPK with the of the D. J. J. D.G. Eur. J. Biochem. J. reported a increase in AMPK activity in the of study by J. Carling D. of AMPK activity found a increase of to a increase of In the the increase in AMPK activity was to AMPK activity the that in this study measured AMPK activity of The AMPK activity, pmol·min−1·μg of is an increase of the the AMPK activity of was the activity in the of this The AMPK activity in the from activation to AMP. in the rat AMP is at to in to Cytosolic AMP to and is at a of J. of AMP to to of J. The in the study in but is AMP the AMPK activity AMP and AMPK to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. and the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 and AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the and activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the of ATP, and by 31P NMR the of cytosolic AMP to in the of 1.8 is with the A0.5 measured in vitro in the of 0.2 mm In the AMPK A0.5 increased 10–20-fold at 4 mm ATP to the of ATP the AMP activation of In the ATP 7 mm. The in the of 7 mm ATP in the suggests of AMPK in the ATP antagonism of AMPK activation is AMPK an ATP that is the cytosolic or factors in to AMP activate AMPK in the heart. to AMP and AMPK to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. and the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 and AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the and activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the of ATP, and by 31P NMR the of cytosolic AMP to in the of 1.8 is with the A0.5 measured in vitro in the of 0.2 mm In the AMPK A0.5 increased 10–20-fold at 4 mm ATP to the of ATP the AMP activation of In the ATP 7 mm. The in the of 7 mm ATP in the suggests of AMPK in the ATP antagonism of AMPK activation is AMPK an ATP that is the cytosolic or factors in to AMP activate AMPK in the heart. to AMP and AMPK to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. to the cytosolic AMP ranged from 0.2 to The A0.5 1.8 AMP suggests that the AMP activation of AMPK in the is low and that AMPK activity is at AMP In vitro the relationship between AMPK activation and AMP the and AMPK an A0.5 to ± and ± Carling D. Biochem. J. measured AMPK activity the to the The of AMPK activity the activation of the AMPK D.G. Biochem. J. a of the AMPK cascade using an A0.5 of 4 AMP that activation in with of D.G. Biochem. J. and Carling D. Biochem. J. found a relationship between AMPK activity and AMP. a between AMPK activity in the of in perfused rat hearts using AMP and ATP measured by high J. Carling D. AMP is the AMP the cytosolic is the of the AMPK cascade of reported by J. Carling D. ATP and the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 mm. ATP the activation of AMPK by AMP ATP with AMP at the but of the D.G. Eur. J. Biochem. of and Carling have that the kinase to the (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref to the ranged from in the to in the with an of The of the AMPK cascade by that of 4 with 0.2 mm ATP increase to at mm ATP D.G. Biochem. J. In vitro of AMPK activity an A0.5 of ± AMP at 0.2 mm ATP, but with 4 mm ATP, the A0.5 was ± D.G. Eur. J. Biochem. The A0.5 of 1.8 in the study the activation of the AMPK cascade in a AMPK in ATP was 7 mm. and AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the heart. AMPK study of AMPK in vitro found that of pH from to in in AMPK activity D.G. Carling D. J. in this study The hearts have a of at and at of the of the the of AMPK activity in this study at 7 increased AMPK activity, this to the AMPK activity in the heart. AMPK and activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK AMPK activity a in the by of activity in the D.G. Eur. J. Biochem. and D.G. J. the of to a in the of acid In and from the the the by In the rat increased AMPK activity with activity In this found a between activity and AMPK of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the of ATP, and by 31P NMR the of cytosolic AMP to in the of 1.8 is with the A0.5 measured in vitro in the of 0.2 mm In the AMPK A0.5 increased 10–20-fold at 4 mm ATP to the of ATP the AMP activation of In the ATP 7 mm. The in the of 7 mm ATP in the suggests of AMPK in the ATP antagonism of AMPK activation is AMPK an ATP that is the cytosolic or factors in to AMP activate AMPK in the heart. to of AMPK in the heart. of activation by AMPK is to a (1Hardie D.G. Carling D. Eur. J. Biochem. 1997; 246: 259-273Crossref or a D.G. J. AMPK to a metabolic and a metabolic is to that the A0.5 activation of AMPK was 1.8 AMP in that from of or in the heart. with AMPK a low that AMPK activation in other D. 1997; reported in the in the
Frederich et al. (Tue,) reported a other. Bromo-octanoate and amino-oxyacetate vs. No inhibitor or inhibitors plus butyrate was evaluated on Relationship between AMPK activity and cytosolic [AMP]. In isolated perfused rat hearts, the half-maximal AMPK activation (A0.5) was 1.8 ± 0.3 μM AMP despite high [ATP], suggesting reduced ATP antagonism of AMPK activation in vivo.
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