CAFFEINE DECREASES MALONYL-COA IN ISOLATED-PERFUSED SKELETAL-MUSCLE OF RATS

The regulation of acetyl-CoA carboxylase and malonyl-CoA levels in ske letal muscle may involve a calcium-dependent mechanism. To examine the effects of increased free sarcoplasmic calcium concentrations on malo nyl-CoA in skeletal muscle, isolated hindlimbs of rats were perfused f or 30 min with a medium containing bovine red blood cells, bovine seru m albumin, 200 mu U/ml insulin, and 10 mM glucose in Krebs-Henseleit b uffer and caffeine at 0, 0.12, 0.5, or 3 mM. Malonyl-CoA decreased fro m control (no caffeine) values of 1.34 +/- 0.9 to 0.95 +/- 0.12 pmol/m g in gastrocnemius-plantaris muscles perfused with 0.12 and 0.5 mM caf feine and to 0.63 +/- 0.07 pmol/mg in the muscles perfused with 3 mM c affeine. Adenosine 3',5'-cyclic monophosphate (cAMP) increased from 0. 24 +/- 0.02 to 0.32 +/- 0.04 nmol/g, and AMP decreased from 83 +/- 8 t o 53 +/- 3 nmol/g in response to 3 mM caffeine. Citrate and ATP were u naffected by caffeine. A decline in malonyl-CoA with 0.12 and 0.5 mM c affeine without an increase in cAMP supports the hypothesis that a cal cium-dependent mechanism of acetyl-CoA carboxylase and malonyl-CoA. re gulation exists, but a cAMP-dependent mechanism may also be involved w ith 3 mM caffeine.