Specific interaction of fatty acyl-CoA esters with brown adipose tissue mitochondria.
The ability of low concentrations of long-chain fatty acyl coenzyme A (CoA) esters to act as inhibitors of purine nucleotide action in hamster brown adipose tissue mitochondria was observed to result from a specific interaction. Palmitoyl-CoA was found to be a competitive inhibitor of nucleotide binding with an apparent Ki of 2.46 +/- 1.09 microM for GDP and 2.98 +/- 0.538 microM for ATP and was able to counteract GDP-inhibited mitochondrial swelling. A minimum acyl-CoA carbon chain length of 12 was necessary for any significant inhibition of GDP binding or induction of swelling to be observed. The effect of palmitoyl-CoA on reversing GDP-inhibited chloride permeability of brown adipose tissue mitochondria was found to be the result of a specific interaction with the brown adipose tissue mitochondrial uncoupling protein. Mitochondria pretreated with N,N'-dicyclohexylcarbodiimide, which binds covalently to the uncoupling protein and partially inhibits brown adipose tissue mitochondrial swelling, underwent a nonspecific increase in swelling in the presence of phenylmercuric acetate. However, with palmitoyl-CoA no further increase in permeability could be mediated. In addition, under certain experimental conditions, palmitoyl-CoA was found to partially inhibit the high halide permeability of brown adipose tissue mitochondria but to a lesser extent than that observed with GDP, suggesting it may be acting as a partial agonist.
P J
PJ
Strieleman
E
E
Shrago
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins; D002712:Chlorides / Q000378:metabolism; D006224:Cricetinae; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D004952:Esters; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008647:Mesocricetus; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D008933:Mitochondrial Swelling / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D002712:Chlorides; D004952:Esters; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate; D010171:Palmitoyl Coenzyme A; D004024:Dicyclohexylcarbodiimide