Abstract

The effect of omeprazole on the mitochondrial carnitine/acylcarnitine transporter has been studied in proteoliposomes.Externally added omeprazole inhibited the carnitine/carnitine antiport catalysed by the transporter. The inhibition waspartially reversed by DTE indicating that it was caused by the covalent reaction of omeprazole with Cys residue(s). Inhibitionof the C-less mutant transporter indicated also the occurrence of an alternative non-covalent mechanism. The IC50 of theinhibition of the WT and the C-less CACT by omeprazole were 5.4 mM and 29 mM, respectively. Inhibition kinetics showednon competitive inhibition of the WT and competitive inhibition of the C-less. The presence of carnitine or acylcarnitinesduring the incubation of the proteoliposomes with omeprazole increased the inhibition. Using site-directed Cys mutants itwas demonstrated that C283 and C136 were essential for covalent inhibition. Molecular docking of omeprazole with CACTindicated the formation of both covalent interactions with C136 and C283 and non-covalent interactions in agreement withthe experimental data.

Autore Pugliese

• Tonazzi Annamaria

Tutti gli autori

• A. Tonazzi; I. Eberini; C. Indiveri

Titolo volume/Rivista

PloS one

Anno di pubblicazione

2013

ISSN

1932-6203

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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