Nicot, CarineRelat Pardo, JoanaWoldegiorgis, GebreHaro Bautista, DiegoMarrero González, Pedro F.2019-06-202019-06-202002-030021-9258https://hdl.handle.net/2445/135597Pig and rat liver carnitine palmitoyltransferase I (L-CPTI) share common K(m) values for palmitoyl-CoA and carnitine. However, they differ widely in their sensitivity to malonyl-CoA inhibition. Thus, pig l-CPTI has an IC(50) for malonyl-CoA of 141 nm, while that of rat L-CPTI is 2 microm. 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.6 p.application/pdfeng(c) American Society for Biochemistry and Molecular Biology, 2002Carnitina palmitoïl-transferasa 1Cinètica enzimàticaAminoàcidsMutagènesiCarnitine palmitoyltransferase IEnzyme kineticsAmino acidsMutagenesisinfo:eu-repo/semantics/article5274472019-06-20info:eu-repo/semantics/openAccess11790778