title: Acetylcholinesterase activity of electric eel is increased or decreased by selected monoterpenoids and phenylpropanoids in a concentration-dependent manner.
abstract: The profitable insecticidal action of monoterpenoids prompted us to test their efficiency against stored-grain beetle species, via inhibition of acetylcholinesterase (AChE). For this, we first studied the ability of the monoterpenoids geraniol, linalool, camphor, fenchone, carvone and γ-terpinene, besides the phenylpropanoids trans-anethole and estragole to inhibit Electrophorus AChE. The results indicated that while AChE activity increased (15-35%) with 40 μM geraniol, camphor, γ-terpinene and linalool, the activity decreased (60-40%) with 5mM carvone, γ-terpinene, and fenchone. The Km for AChE was 0.52 ± 0.02 mM in control assays, which fell to 0.28 ± 0.01 mM or 0.32 ± 0.01 mM in assays with 20 μM linalool or γ-terpinene added. In the millimolar range, the terpenoids behaved as weak inhibitors. Unexpectedly, AChE inhibition by camphor, carvone, γ-terpinene, and fenchone gave Hill numbers ranging 2.04-1.57, supporting the idea that AChE was able to lodge more than one monoterpenoid molecule. The plots of 1/v vs. 1/S at varying monoterpenoid provided straight lines, fenchone and γ-terpinene acting as competitive inhibitors and carvone and camphor as non-competitive inhibitors. Moreover, the secondary plots of the slope KM(app)/Vmax(app) vs. [I] and of 1/Vmax(app) vs. [I] gave parabolic curves, which lent support to the proposed capacity of AChE to bind more than one monoterpenoid molecule. The fitting of the curves to a second-order polynomial equation allowed us to calculate the inhibition constants for the interaction of AChE with fenchone, γ-terpinene, carvone and camphor. The previously unnoticed increase in AChE activity with monoterpenoids should be considered as a reminder when advising the use of essential oils of plants or their constituents as anti-AChE agents to attenuate pathological signs of Alzheimer's disease.
authors: Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), Universidad de Murcia, IMIB-Arrixaca, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors: María Dolores
authors: MD
authors: López
authors: Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, IMIB-Arrixaca, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors: Francisco J
authors: FJ
authors: Campoy
authors: Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), Universidad de Murcia, IMIB-Arrixaca, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors: María Jesús
authors: MJ
authors: Pascual-Villalobos
authors: Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, IMIB-Arrixaca, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors: Encarnación
authors: E
authors: Muñoz-Delgado
authors: Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, IMIB-Arrixaca, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain. Electronic address: cevidal@um.es.
authors: Cecilio J
authors: CJ
authors: Vidal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004593:Electrophorus / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects*; D029941:Fish Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000840:Anisoles; D002800:Cholinesterase Inhibitors; D029941:Fish Proteins; D039821:Monoterpenes; D009822:Oils, Volatile; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase activation; Alzheimer’s disease; Cooperative binding; Essential oils