Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line.
The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK to phosphorylate and inactivate acetyl-CoA carboxylase (ACC), reducing malonyl-CoA formation. It has been suggested that AMPK may also regulate malonyl-CoA content by activation of malonyl-CoA decarboxylase (MCD). We have investigated the potential regulation of MCD by AMPK in exercising skeletal muscle, in an islet cell line, and in vitro. Three rat fast-twitch muscle types were studied using two different contraction methods or after exposure to the AMPK activator AICAR. Although all muscle treatments resulted in activation of AMPK and phosphorylation of ACC, no stimulus had any effect on MCD activity. In 832/13 INS-1 rat islet cells, two treatments that result in the activation of AMPK, namely low glucose and AICAR, also had no discernable effect on MCD activity. Last, AMPK did not phosphorylate in vitro either recombinant MCD or MCD immunoprecipitated from skeletal muscle or heart. We conclude that MCD is not a substrate for AMPK in fast-twitch muscle or the 832/13 INS-1 islet cell line and that the principal mechanism by which AMPK regulates malonyl-CoA content is through its regulation of ACC.
Habinowski
S A
SA
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Hirshman
M
M
Sakamoto
K
K
Kemp
B E
BE
Gould
S J
SJ
Goodyear
L J
LJ
Witters
L A
LA
D055372:AMP-Activated Protein Kinases; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012584:Sciatic Nerve; D013379:Substrate Specificity
D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase