RESUMEN
Cholinesterases are a large family of enzymatic proteins widely distributed throughout both neuronal and non-neuronal tissues. In Alzheimer's disease (AD), analytical as well as epidemiological studies suggest an implication of an abnormal focal accumulation of aluminum in the brain. In this devastating disease, aluminum may interfere with various biochemical processes including acetylcholine metabolism, and can thus act as a possible etiopathogenic cofactor. Acetylcholinesterase (AChE) exists in several molecular forms that differ in solubility and mode of membrane attachment rather than in catalytic activity. Mice were treated orally with aluminum chloride or aluminum lactate (Al(lac)(3)), and AChE activity in their brain homogenates was then assayed. Results showed that this in vivo treatment augmented the activity of the enzyme. An activating effect was also observed in vitro, when the aluminum compounds were added directly to mouse brain homogenates. However, the activating effect observed in vivo was much more marked than that observed in vitro. In addition, the activation produced by Al(lac)(3) was higher than that obtained after aluminum chloride treatment. Kinetics measurements of AChE activity in the absence and presence of treatment with aluminum both in vivo and in vitro are reported. The influence of the metal speciation on enzymatic activity is discussed in relation to a possible implication of aluminum in some neurodegenerative diseases.
Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Compuestos de Aluminio/toxicidad , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/enzimología , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Fibras Colinérgicas/efectos de los fármacos , Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Cloruro de Aluminio , Enfermedad de Alzheimer/fisiopatología , Animales , Encéfalo/fisiopatología , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Cloruros/toxicidad , Fibras Colinérgicas/enzimología , Fibras Colinérgicas/patología , Colinesterasas/farmacología , Lactatos/toxicidad , Ratones , Neuronas/efectos de los fármacos , Neuronas/enzimología , Fracciones Subcelulares , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Tacrina/farmacologíaRESUMEN
The speciation of the toxic Al(III) and the beneficial VO(IV) in various biofluids and tissues is discussed in order to describe the solution state of these metal ions in the organism. The possibility and the importance of ternary complex formation with relevant biomolecules is emphasised. The importance of the biospeciation of Al(III) ion in its transport and involvement in neurological disorders, and of insulin mimetic VO(IV) complexes is discussed.