Activation/deactivation of Carnitine Palmotoyltransferase 1A: An insight from Molecular Dynamics Simulations

PANTANO, SERGIO; BARRERA, EXEQUIEL E.; FRIGINI, EZEQUIEL N.; PORASSO, RODOLFO D.

La Plata

Congreso; XLVII Reunión Anual de la Sociendad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

Carnitine Palmitoyltransferase 1A (CPT1A) is an enzyme that is anchored in the outer mitochondrial membrane (OMM). This enzyme controls the passage of fatty acids into the mitochondria and then enters the process of β-oxidation of a long-chain fatty acids. The CPT1A is inhibited by malonyl-CoA, the first intermediate of the synthesis of fatty acids, and responds to: (i) the curvature of the OMM and (ii) lipid characteristics for its activation and deactivation. The experimental results on the enzyme show that its N-terminal domain adopts two states: activated or deactivated. The purpose of this study was to elucidate a mechanism of regulation of the enzyme CPT1A by simulations of molecular dynamics (MD). The lipids used for bilayer models were palmitoyl-oleoyl phosphatidycholine (POPC) and palmitoyloleoyl phosphatidylethanolamine (POPE) in the presence/absence of the enzyme. Four simulations of MD were carried out: (i) lipid bilayer mixtures (without restraint), (ii) lipid bilayer mixtures (with restraint on POPE), (iii) lipid bilayer mixtures + enzyme (without restraint) and (iv) lipid bilayer mixtures + enzyme (with restraint on POPE). Our results showed that the bilayer with restraint have a greater curvature with respect to the bilayer without restraint. The results of this study show the influence of bilayer curvature, inducing the state of deactivation when the bilayer is flat (without restraint) and activating CPT1A when the bilayer is curved (with restraint).