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Malonyl CoA as a metabolic switch and a regulator of insulin sensitivity

Abstract

Malonyl CoA is a regulator of carnitine palmitoyl transferase 1 (CPT1), the enzyme that controls the transfer of long chain fatty acyl CoA into mitochondria where it is oxidized. Recent studies indicate that in skeletal muscle the concentration of malonyl CoA is acutely (minutes) regulated by changes in its fuel supply and energy expenditure. In response to changes in fuel supply, regulation appears to be due to alterations in the cytosolic concentration of citrate, which is both an allosteric activator of acetyl CoA carboxylase (ACC), the enzyme that catalyzes malonyl CoA synthesis and a source of its precursor, cytosolic acetyl CoA. During exercise and immediately thereafter regulation by citrate appears to be lost and malonyl CoA levels diminish as the result of a decrease in ACC activity secondary to phosphorylation. Sustained increases in the concentration of malonyl CoA have been observed in muscle of a number of insulin-resistant rodents including the Zucker (fa/fa) and GK rats, KKAgy mice, glucose-infused rats and rats in which muscle has been made insulin resistant by denervation. Available data suggest that malonyl CoA could be linked to insulin resistance in these rodents by virtue of its effects on the cytosolic concentration of long chain fatty acyl CoA (LCFA CoA) and one or more protein kinase C isozymes. Whether similar alterations occur in other tissues and contribute to the pathophysiology of the insulin resistance syndrome remains to be determined.

Type Journal
ISBN 0065-2598 (Print)
Authors Ruderman, N. B.;Saha, A. K.;Vavvas, D.;Kurowski, T.;Laybutt, D. R.;Schmitz-Peiffer, C.;Biden, T.;Kraegen, E. W. :
Garvan Authors A/Prof Ross Laybutt , Prof Ted Kraegen
Publisher Name ADV EXP MED BIOL
Published Date 1998-01-01 00:00:00
Published Volume 441
Published Pages 263-70
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9781332
Status Published In-print