Effect of pH and acyl-CoA chain length on the conversion of heart mitochondrial CPT-I/CPTo to a high affinity, malonyl-CoA-inhibited state.
The effect of pH and acyl-CoA chain length on the conversion of the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPT-I/CPTo) to a high-affinity, malonyl-CoA-inhibited state using a particle derived from rat heart mitochondria was determined. Preincubation with malonyl-CoA for one minute in the absence of acyl-CoA substrate lowers the IC50 for malonyl-CoA from 2 microM, 14 microM, and 15 microM at pH 7.4 to 15 nM, 14 nM, and 14 nM for decanyl-, lauryl-, and palmitoyl-CoA, respectively. Reducing the pH to 7.1 and 6.8 had little effect on the transition to the high affinity, malonyl-CoA-inhibited state. Preincubation of malonyl-CoA with the acyl-CoA, but not with L-carnitine, prevented the transition to the high affinity, malonyl-CoA-inhibited state.
Bieber
L L
LL
Department of Biochemistry, Michigan State University, East Lansing 48824, USA.
Wagner
M
M
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000201:enzymology*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D051381:Rats
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; C045561:decanoyl-coenzyme A; D010171:Palmitoyl Coenzyme A; D008316:Malonyl Coenzyme A; C050466:lauroyl-coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine