Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside

J Biol Chem. 2000 Aug 11;275(32):24279-83. doi: 10.1074/jbc.C000291200.


Alterations in the concentration of malonyl-CoA, an inhibitor of carnitine palmitoyltransferase I, have been linked to the regulation of fatty acid oxidation in skeletal muscle. During contraction decreases in muscle malonyl-CoA concentration have been related to activation of AMP-activated protein kinase (AMPK), which phosphorylates and inhibits acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in malonyl-CoA formation. We report here that the activity of malonyl-CoA decarboxylase (MCD) is increased in contracting muscle. Using either immunopurified enzyme or enzyme partially purified by (NH(4))(2)SO(4) precipitation, 2-3-fold increases in the V(max) of MCD and a 40% decrease in its K(m) for malonyl-CoA (190 versus 119 micrometer) were observed in rat gastrocnemius muscle after 5 min of contraction, induced by electrical stimulation of the sciatic nerve. The increase in MCD activity was markedly diminished when immunopurified enzyme was treated with protein phosphatase 2A or when phosphatase inhibitors were omitted from the homogenizing solution and assay mixture. Incubation of extensor digitorum longus muscle for 1 h with 2 mm 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, a cell-permeable activator of AMPK, increased MCD activity 2-fold. Here, too, addition of protein phosphatase 2A to the immunopellets reversed the increase of MCD activity. The results strongly suggest that activation of AMPK during muscle contraction leads to phosphorylation of MCD and an increase in its activity. They also suggest a dual control of malonyl-CoA concentration by ACC and MCD, via AMPK, during exercise.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylate Kinase / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Carboxy-Lyases / isolation & purification
  • Carboxy-Lyases / metabolism*
  • Kinetics
  • Male
  • Muscle Contraction / physiology*
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / innervation
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Phosphatase 2
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology*
  • Sciatic Nerve / physiology


  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Adenylate Kinase
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Carboxy-Lyases
  • malonyl-CoA decarboxylase
  • AICA ribonucleotide