COMPARISON OF THE EFFECTS OF CARNITINE PALMITOYLTRANSFERASE-1 AND PALMITOYLTRANSFERASE-2 INHIBITORS ON RAT-HEART HYPERTROPHY

Rats treated orally for 21 days with aminocarnitine, an inhibitor of c arnitine palmitoyltransferase-2 (CPT-2), do not show hypertrophy of th e heart. This contrasts with the effects of carnitine palmitoyltransfe rase-1 (CPT-1) inhibitors, that, according to the literature cause hyp ertrophy. As CPT-1 and CPT-2 are both required for the oxidation of lo ng-chain fatty acids in mitochondria, it can be concluded that inhibit ion of fatty acid oxidation per se is not responsible for cell growth, but rather the accumulation of a metabolite, probably long-chain acyl coenzyme A. CPT-1 and CPT-2 inhibitors cause different metabolic chang es in the heart. Electron microscopy of hearts fixed 1 hour after Lang endorff perfusion with the two types of inhibitors reveals some of the se changes. Multilamellar vesicles were observed with aminocarnitine ( CPT-2 inhibitor) but not with etomoxir (CPT-1 inhibitor). When both in hibitors were present, electron-dense spots adjacent to mitochondria w ere observed, possibly containing long-chain acylaminocarnitine.