Pig Liver Carnitine Palmitoyltransferase

• Published in: The Journal of biological chemistry Vol. 277; no. 12; pp. 10044 - 10049
• Main Authors: Nicot, Carine, Relat, Joana, Woldegiorgis, Gebre, Haro, Diego, Marrero, Pedro F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 22.03.2002; American Society for Biochemistry and Molecular Biology
• DOI: 10.1074/jbc.M109976200
• ISSN: 0021-9258

Pig and rat liver carnitine palmitoyltransferase I (L-CPTI) share common Km values for palmitoyl-CoA and carnitine. However, they differ widely in their sensitivity to malonyl-CoA inhibition. Thus, pig l-CPTI has an IC50 for malonyl-CoA of 141 nm, while that of rat L-CPTI is 2 μm. Using chimeras between rat L-CPTI and pig L-CPTI, we show that the entire C-terminal region behaves as a single domain, which dictates the overall malonyl-CoA sensitivity of this enzyme. The degree of malonyl-CoA sensitivity is determined by the structure adopted by this domain. Using deletion mutation analysis, we show that malonyl-CoA sensitivity also depends on the interaction of this single domain with the first 18 N-terminal amino acid residues. We conclude that pig and rat L-CPTI have different malonyl-CoA sensitivity, because the first 18 N-terminal amino acid residues interact differently with the C-terminal domain. This is the first study that describes how interactions between the C- and N-terminal regions can determine the malonyl-CoA sensitivity of L-CPTI enzymes using active C-terminal chimeras.