Effects of hypoxia and fatty acids on the distribution of metabolites in rat heart.
The effects of exogenous fatty acids and hypoxia on cardiac energy metabolism were studied by measuring mitochondrial and cytosolic adenine nucleotides as well as CoA and carnitine esters using a tissue fractionation technique in non-aqueous solvents. During normoxia, the administration of 0.5 mM palmitate caused a considerable increase in acyl-CoA and acylcarnitine, particularly in mitochondria. High-energy phosphates, however, were only slightly altered. A 90 min low-flow hypoxia caused a dramatic increase in mitochondrial acyl esters. The mitochondrial ATP content decreased significantly, while the cytosolic concentration was only slightly diminished, suggesting an inhibition of mitochondrial adenine nucleotide translocation by long-chain acyl-CoA. Addition of palmitate during hypoxia amplified hypoxic damage and reduced adenine nucleotides in both compartments considerably, while fatty acid metabolites were only slightly affected. In presence of an inhibitor of fatty acid oxidation (BM 42.304), the fatty-acid-induced acceleration of cardiac injury was prevented. Since BM 42.304 decreased mitochondrial acylcarnitine and increased the cytosolic concentration significantly, BM 42.304 was presumed to inhibit mitochondrial acylcarnitine translocase. However, a causal relationship between lipid metabolites and ischemic damage seemed unlikely.
Hütter
J F
JF
Zentrum Physiologie und Pathophysiologie, Universität Göttingen, F.R.G.
Alves
C
C
Soboll
S
S
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology; D003065:Coenzyme A / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000502:physiology*; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D002934:Cinnamates; D005227:Fatty Acids; D010710:Phosphates; C039804:BM 42304; D002331:Carnitine; D010100:Oxygen; D003065:Coenzyme A