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.