Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.3/2748
Título: Diagnosis of Enzyme Inhibition Based on the Degree of Inhibition
Autor: Antunes, Fernando
Marinho, Helena Susana
Barreto, Maria do Carmo
Pavão, Maria Leonor
Pinto, Ruy Eugénio
Palavras-chave: Linear and Hyperbolic Inhibition
Parabolic and Rational 2,2 Inhibition
Acid Phosphatase
Data: Dez-2003
Editora: Elsevier
Citação: ANTUNES, F., MARINHO, H. S., BARRETO, M. C., PAVÃO, M. L. e PINTO, R. E. (2003). "Diagnosis of Enzyme Inhibition Based on the Degree of Inhibition". Biochimica et Biophysica Acta, 1624(1-3): 11-20. http://dx.doi.org/10.1016/j.bbagen.2003.08.007.
Resumo: In this work, a method for the diagnosis of kinetic inhibition, based on the dependence of the degree of inhibition (s) on the inhibitor concentration [1] and on the substrate concentration [S], is presented. Because the degree of inhibition is a ratio between rates, kinetic data are normalized by the introduction of an internal control-the rate of the uninhibited reaction. Therefore, the error associated with the kinetic measurements decreases and less experimental measurements are necessary to achieve the diagnosis. The process described, which uses graphical and/or non-linear fitting procedures, allows distinguishing between 20 different kinds of inhibition, including not only linear and hyperbolic, but also parabolic and rational 2,2 inhibitions. Rational 2,2 indicates a new type of inhibition corresponding to an incomplete parabolic inhibition, i.e. mechanistically it corresponds to an inhibitor that binds to two inhibition sites producing enzymatic complexes that are still active. In spite of its comprehensiveness, the diagnosis process is greatly facilitated by the division of the diagnosis of the inhibition in a step-by-step procedure, where only two rival models are evaluated in each step. In the non-linear fittings, the choice between rival models uses a test based on information statistics theory, the Akaike information criterion test, in order to penalize complex models that tend to be favoured in fittings. Finally, equations that allow the determination of inhibition kinetic constants were also deduced. The formalism presented was tested by examining inhibition of acid phosphatase by phosphate (a linear competitive inhibitor).
Descrição: Copyright © 2003 Elsevier B.V. All rights reserved.
Peer review: yes
URI: http://hdl.handle.net/10400.3/2748
ISSN: 0006-3002
Versão do Editor: http://www.sciencedirect.com/science/journal/03044165/1624/1
Aparece nas colecções:DCFQE - Artigos em Revistas Internacionais / Articles in International Journals

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