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Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition
dc.contributor.author | Morillas, Montserrat | |
dc.contributor.author | Gómez-Puertas, Paulino | |
dc.contributor.author | Bentebibel, Assia | |
dc.contributor.author | Sellés, Eva | |
dc.contributor.author | Casals i Farré, Núria | |
dc.contributor.author | Valencia, Alfonso | |
dc.contributor.author | Hegardt, Fausto G. | |
dc.contributor.author | Asins, Guillermina | |
dc.contributor.author | Serra, Dolors | |
dc.date.accessioned | 2021-05-05T15:15:30Z | |
dc.date.available | 2021-05-05T15:15:30Z | |
dc.date.issued | 2003-03-14 | |
dc.identifier.citation | Morillas, Montserrat; Gómez-Puertas, Paulino; Bentebibel, Assia [et al.]. Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition. Journal of Biological Chemistry, 2003, 278(11), p. 9058-9063. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925819712745?via%3Dihub>. Fecha de acceso: 5 may. 2021. DOI: 10.1074/jbc.M209999200 | ca |
dc.identifier.issn | 0021-9258 | ca |
dc.identifier.uri | http://hdl.handle.net/20.500.12328/2520 | |
dc.description.abstract | Carnitine palmitoyltransferase (CPT) I, which catalyzes the conversion of palmitoyl-CoA to palmitoylcarnitine facilitating its transport through the mitochondrial membranes, is inhibited by malonyl-CoA. By using the SequenceSpace algorithm program to identify amino acids that participate in malonyl-CoA inhibition in all carnitine acyltransferases, we found 5 conserved amino acids (Thr314, Asn464, Ala478, Met593, and Cys608, rat liver CPT I coordinates) common to inhibitable malonyl-CoA acyltransferases (carnitine octanoyltransferase and CPT I), and absent in noninhibitable malonyl-CoA acyltransferases (CPT II, carnitine acetyltransferase (CAT) and choline acetyltransferase (ChAT)). To determine the role of these amino acid residues in malonyl-CoA inhibition, we prepared the quintuple mutant CPT I T314S/N464D/A478G/M593S/C608A as well as five single mutants CPT I T314S, N464D, A478G, M593S, and C608A. In each case the CPT I amino acid selected was mutated to that present in the same homologous position in CPT II, CAT, and ChAT. Because mutant M593S nearly abolished the sensitivity to malonyl-CoA, two other Met593mutants were prepared: M593A and M593E. The catalytic efficiency (V max/K m) of CPT I in mutants A478G and C608A and all Met593 mutants toward carnitine as substrate was clearly increased. In those CPT I proteins in which Met593 had been mutated, the malonyl-CoA sensitivity was nearly abolished. Mutations in Ala478, Cys608, and Thr314 to their homologous amino acid residues in CPT II, CAT, and ChAT caused various decreases in malonyl-CoA sensitivity. Ala478 is located in the structural model of CPT I near the catalytic site and participates in the binding of malonyl-CoA in the low affinity site (Morillas, M., Gómez-Puertas, P., Rubı́, B., Clotet, J., Ariño, J., Valencia, A., Hegardt, F. G., Serra, D., and Asins, G. (2002) J. Biol. Chem. 277, 11473–11480). Met593 may participate in the interaction of malonyl-CoA in the second affinity site, whose location has not been reported. | en |
dc.format.extent | 6 | ca |
dc.language.iso | eng | ca |
dc.publisher | American Society for Biochemistry and Molecular Biology | ca |
dc.relation.ispartof | Journal of Biological Chemistry | ca |
dc.relation.ispartofseries | 278;11 | |
dc.rights | Under a Creative Commons license. This is an Open Access article under theCC BY license. | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject.other | Mutació (Biologia) | ca |
dc.subject.other | Mitocondris | ca |
dc.subject.other | Enzims | ca |
dc.subject.other | Metabolisme -- Trastorns | ca |
dc.subject.other | Aminoàcids -- Metabolisme | ca |
dc.subject.other | Mutación (Biología) | es |
dc.subject.other | Mitocondrias | es |
dc.subject.other | Enzimas | es |
dc.subject.other | Metabolismo -- Trastornos | es |
dc.subject.other | Aminoácidos -- Metabolismo | es |
dc.subject.other | Mutation (Biology) | en |
dc.subject.other | Mitochondria | en |
dc.subject.other | Enzymes | en |
dc.subject.other | Metabolism -- Disorders | en |
dc.subject.other | Amino acids -- Metabolism | en |
dc.title | Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition | en |
dc.type | info:eu-repo/semantics/article | ca |
dc.description.version | info:eu-repo/semantics/publishedVersion | ca |
dc.rights.accessLevel | info:eu-repo/semantics/openAccess | |
dc.embargo.terms | cap | ca |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/1PN/ES/1PN/BMC2001-3048 | ca |
dc.subject.udc | 57 | ca |
dc.subject.udc | 61 | ca |
dc.identifier.doi | https://dx.doi.org/10.1074/jbc.M209999200 | ca |
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