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, B. B. Rasmussen, C. A. Hutber, G. B. Call, R. D. Clayton, L. M. Conley, S. Yoon, B. Zhou

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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
DOIs
StatePublished - Jan 1997
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Winder, W. W., Wilson, H. A., Hardie, D. G., Rasmussen, B. B., Hutber, C. A., Call, G. B., Clayton, R. D., Conley, L. M., 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, 82(1), 219-225. https://doi.org/10.1152/jappl.1997.82.1.219