Pig liver carnitine palmitoyltransferase I, with low K-m for carnitine andhigh sensitivity to malonyl-CoA inhibition, is a natural chimera of rat liver and muscle enzymes

The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (C PTI) catalyzes the initial and regulatory step in the beta -oxidation of fa tty acids. The genes for the two isoforms of CPTI-liver (L-CPTI) and muscle (M-CPTI) have been cloned and expressed, and the genes encode for enzymes with very different kinetic properties and sensitivity to malonyl-CoA inhib ition. Pig L-CPTI encodes for a 772 amino acid protein that shares 86 and 6 2% identity, respectively, with rat L- and M-CPTI. When expressed in Pichia pastoris, the pig L-CPTI enzyme shows kinetic characteristics (carnitine, K-m = 126 muM; palmitoyl-CoA, K-m = 35 muM) similar to human or rat L-CPTI. However, the pig enzyme, unlike the rat liver enzyme, shows a much higher sensitivity to malonyl-CoA inhibition (IC50 = 141 nM) that is characteristi c of human or rat M-CPTI enzymes. Therefore, pig L-CPTI behaves like a natu ral chimera of the L- and M-CPTI isotypes, which makes it a useful model to study the structure-function relationships of the CPTI enzymes.