Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A

W. W. Winder, H. A. Wilson, D. G. Hardie, Blake Rasmussen, C. A. Hutber, G. B. Call, R. D. Clayton, L. M. Conley, S. Yoon, B. Zhou

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

This study was designed to compare functional effects of phosphorylation of muscle acetyl-CoA carboxylase (ACC) by adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and by AMP-activated protein kinase (AMPK). Muscle ACC (272 kDa) was phosphorylated and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. Functional effects of phosphorylation were determined by measuring ACC activity at different concentrations of each of the substrates and of citrate, an activator of the enzyme. The maximal velocity (V(max)) and the Michaelis constants (K(m)) for ATP, acetyl-CoA, and bicarbonate were unaffected by phosphorylation by PKA. Phosphorylation by AMPK increased the K(m) (for) ATP and acetyl-CoA. Sequential phosphorylation by PKA and AMPK, first without label and second with label, appeared to reduce the extent of label incorporation, regardless of the order. The activation constant (K(a)) for citrate activation was increased to the same extent by AMPK phosphorylation, regardless of previous or subsequent phosphorylation by PKA. Thus muscle ACC can be phosphorylated by PKA but with no apparent functional effects on the enzyme. AMPK appears to be the more important regulator of muscle ACC.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalJournal of Applied Physiology
Volume82
Issue number1
StatePublished - Jan 1997
Externally publishedYes

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Acetyl-CoA Carboxylase
AMP-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Protein Kinases
Muscles
Acetyl Coenzyme A
Citric Acid
Adenosine Triphosphate
Enzyme Activators
Bicarbonates
AMP-activated protein kinase kinase
Autoradiography
Sodium Dodecyl Sulfate
Cyclic AMP
Polyacrylamide Gel Electrophoresis
Enzymes

Keywords

  • carnitine palmitoyl transferase
  • fatty acid oxidation by muscle
  • malonyl- CoA

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Winder, W. W., Wilson, H. A., Hardie, D. G., Rasmussen, B., Hutber, C. A., Call, G. B., ... Zhou, B. (1997). Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. Journal of Applied Physiology, 82(1), 219-225.

Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. / Winder, W. W.; Wilson, H. A.; Hardie, D. G.; Rasmussen, Blake; Hutber, C. A.; Call, G. B.; Clayton, R. D.; Conley, L. M.; Yoon, S.; Zhou, B.

In: Journal of Applied Physiology, Vol. 82, No. 1, 01.1997, p. 219-225.

Research output: Contribution to journalArticle

Winder, WW, Wilson, HA, Hardie, DG, Rasmussen, B, Hutber, CA, Call, GB, Clayton, RD, Conley, LM, Yoon, S & Zhou, B 1997, 'Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A', Journal of Applied Physiology, vol. 82, no. 1, pp. 219-225.
Winder, W. W. ; Wilson, H. A. ; Hardie, D. G. ; Rasmussen, Blake ; Hutber, C. A. ; Call, G. B. ; Clayton, R. D. ; Conley, L. M. ; Yoon, S. ; Zhou, B. / Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. In: Journal of Applied Physiology. 1997 ; Vol. 82, No. 1. pp. 219-225.
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